The Pharma World

INTERVIEW

The healthcare professionals in our country
are continuously managing the health hazards
with utmost sincerity and devotion

Prof. Dr. Md. Anwarul Kabir As an eminent Gastroenterologist recent past, there was another variant
Chairman of the country, would you please of chronic pancreatitis known as FCCP
Dept. of Gastroenterology tell us about the gastrointestinal, (Fibro calcific chronic pancreatitis).
BSMMU, Dhaka pancreato-biliary and liver It was mostly due to malnutrition.
diseases in our country? Chronic pancreatitis may present with
deficiency of pancreatic enzymes
Bangladesh is a tropical coun- leading to malabsorption syndrome
try. We have a primitive sanitation and diabetes mellitus.
system. There is no supply of safe
drinking water. We have no knowl- Diseases of the biliary tree are
edge about the food hygiene and congenital anomalies (choledocal
sanitation. Both the restaurant staffs cyst, caroli’s disease and bile duct
and its customers are unaware of stricture). Stone in the gallblad-
food sanitation, preservation, and der and bile duct is a very common
safe delivery of food. It makes us disorder. Strictures of the bile duct
prone to waterborne and food borne are due to surgery and inflammatory
diseases throughout the year like di- (stone induced) causes are also com-
arrhoea, dysentery, bloody diarrhoea monly encountered.
and other GI infections. Jaundice of
various types like A and E are com- Gastrointestinal tract starts from
monly prevalent. Peptic ulcer disease mouth and extends up to the anal
and irritable bowel syndrome are orifice. It has some associated organs
common problems in the western like liver, pancreas, gallbladder and
world, though our people frequently bile duct. All these organs lead to
encounter this problem. Liver ab- multiple cancers. Most common can-
scess and round worm (ascariasis) in cer of the GI tract is the cancer of the
the common bile duct are common stomach. It is the second most com-
as well. These are the common gas- mon cancer in the body next to lung
trointestinal and liver diseases in our cancer in male. Others are colo-rectal
country. These are few examples of cancer (large bowel and rectum) ,
common GI problems we frequently Oesophageal carcinoma, duodenal
encounter in our daily practice. adenocarcinoma(duodenum), hepa-
tocellular carcinoma, pancreatic car-
Most common pancreatic disorder cinoma, gallbladder carcinoma and
is acute pancreatitis and its complica- chloangicarcinoma (bile duct). All
tions. In western world it is mainly these cancers are frequently found in
due to alcoholism. But, since rice is our daily practices.
our staple food, blood TG level is high
in our population. High triglyceride is In light of the recent COVID-19
one of the major causes of acute pan- pandemic, does pre-existing GI
creatitis in our country. Most cases disorders pose a greater risk for
resolve spontaneously but, certain COVID-19 complications? What
percentages have some deadly com- are the GI symptoms to look
plications with high mortality rate. out for? What measures do you
Repeated attacks of acute pancrea- recommend for its management?
titis lead to chronic pancreatitis. In
As COVID 19 is a newer disease

THE PHARMA WORLD 51



INTERVIEW

there are variable data regarding as- 6. Gut dysbiosis occurs in COVID-19 7. Chewing gum
sociation of preexisting GI disorder which alters gut-lung axis and can 8. Sedentary lifestyle
and COVID complications. As far we severe the disease. Probiotics can 9. Genetic predisposition
know, some patients with GI disease shorten the duration of disease
may be at increased risk for more and reduce the rate of ventila- Symptoms of irritable bowel syndrome-
severe illness. Potential risk factors tor associated pneumonia in ICU. 1. Chronic abdominal pain — De-
include chronic inflammatory bowel Fecal Macrobiotic Transplantation
disease, comorbidities (DM) and use can be useful. scribed as a cramping sensa-
of glucocorticoids. Corticosteroid tion with variable intensity and
use is associated with more adverse What are the trigger factors periodic exacerbations. Location
outcome and requires more ICU and symptoms of Irritable and character of the pain can vary
care, ventilation. Patients with viral Bowel Syndrome (IBS)? Is it widely. Severity of the pain may
hepatitis and NAFLD with COVID-19 preventable? What changes of range from mild to severe. Pain is
has greater risk of developing severe diet can help patients with IBS? frequently related to defecation.
disease. Cirrhosis of liver has greater In some patients abdominal pain
mortality (36%), which is significantly Irritable bowel syndrome (IBS) is a is relieved with defecation, some
higher than chronic non cirrhotic gastrointestinal disorder character- patients report worsening of pain
liver disease (7%) or patients of ized by chronic abdominal pain and with defecation.
liver transplantation (20%). Acute altered bowel habits due to an al- 2. Emotional stress and meals may
pancreatitis with COVID-19 patients tered interaction of the brain-gut axis, exacerbate the pain
is more frequently related to the in the absence of any organic cause. 3. Abdominal bloating
severe systemic disease and multi 4. Increased gas production in the
organ complications and have higher Trigger factors of IBS- form of flatulence or belching
mortality. Some data suggest proton 1. Dietary triggers- 5. Alteration of bowel habit-
pump inhibitor increase the risk of a. Diarrhoea: Frequent loose stools
COVID-19 infection. a. For diarrhea predominant
IBS, trigger factors are high of small to moderate volume
GI symptoms to look for: fiber diet, Chocolate, alcohol, which may occur during waking
About one third of patients may caffeine, fructose, or sorbitol, hours, most often in the morn-
Carbonated drinks, Fried and ing or after meals. May be as-
present with GI symptoms. The symp- fatty foods, dairy products, sociated with mucous discharge.
toms are : Anorexia most common especially if lactose intolerant No nocturnal episodes. Most
(26.8%), diarrhea (12.5 %), nausea, and wheat for people who are bowel movements are preceded
vomiting (10.2 %), Abdominal pain allergic to gluten by lower abdominal cramping
(9.2 %). pain, urgency, and a sensation
b. For constipation predominant of incomplete evacuation.
Other common complications in- IBS, trigger factors include, b. Constipation- Less than 3 bowel
clude acute liver injury and elevated breads and cereals made with movements per week which may
transaminases, acute acalculous refined grains, processed foods be associated with straining.
cholecystitis, acute pancreatitis, ileus (ex. chips and cookies), coffee, Hard and pellet shaped stools.
and feeding intolerance, acute co- carbonated drinks, alcohol, May have sense of incomplete
lonic pseudo-obstruction, mesenteric high-protein diets, dairy prod- evacuation. May be associated
ischemia etc. ucts, especially cheese. with anorectal blockage requir-
ing manual maneuvers.
Recommendation for management : 2. Psychological trigger factors –
1. No specific management for GI anxiety, stress, depression Although IBS is not a preventable
disease, certain dietary and lifestyle
symptoms. 3. Menstruation modifications along with adjunctive
2. Management of COVID 19. 4. Medication- Drugs that can trigger therapies can help to control the dis-
3. Supportive management: ease symptoms to a great extent.
IBS include, antibiotics (due to
- Management of nutrition alteration of the gut microbiota), Dietary modifications in IBS patients-
- Management of hydration Anti-depressants (selective), A careful and meticulous history
- Management of electrolyte Sorbitol containing drugs (ex-
cough syrup) should be taken regarding the symp-
imbalance 5. Acute infection – post infectious IBS tom pattern related to specific foods.
4. If diarrhea present: Loperamide, 6. Poor eating habits – Such as chew- Care must be taken to avoid those
ing too quickly, eating large meals
Anti secretory (racecadotril) etc
5. If vomiting: Anti emetic

THE PHARMA WORLD 53

INTERVIEW

food groups particularly. in the pathogenesis of PUD. Marshall the addition of antimicrobial has
1. Exclusion of gas producing and Warren in 1984 discovered a changed the treatment strategy. In
gram negative bacteria (H.pylori) in one hand they eradicate the bacteria
foods- Patients with IBS should the gastric mucosa. And it is associ- and in other hand they profoundly
be advised to exclude foods that ated with gastritis, ulcer disease, suppress acid secretion and prevent
increase flatulence. gastric cancer and MALToma. With the complications and recurrences.
Ex. Beans, onions, celery, carrots, this discovery there is a great revolu-
raisins, bananas, apricots, prunes, tion in the field of gastroenterology. Being available over the counter,
Brussels sprouts, wheat germ, This is the most common bacteria patients now a days are self
alcohol, caffeine etc. infecting half of the population of prescribing and overusing anti-
2. Lactose and gluten avoidance the world. H.pylori is transmitted ulcerant drugs like PPIs. What
3. Low FODMAP diet-The elimination by faeco-oral route. It is commonly are the consequences of such
of dietary fermentable oligosac- found where sanitation is poor and irrational use in long term?
charides, disaccharides, monosac- other water borne diseases are very
charides and polyols(FODMAPs) common. It is also common in our Proton pump inhibitor (PPI) are
has quickly gained popularity as country with 95% infection occuring Omeprozole, Lansoprazole and
a treatment for patients with IBS. in children by the age of five (ICDDRB Pantoprazole etc. They are commonly
FODMAPs lead to increased GI study). prescribed by doctors logically and
water secretion and increased fer- empirically. It is widely marketed and
mentation in the colon, thus pro- After the discovery of H.pylori the highly prescribed throughout the
ducing short chain fatty acids and aetiopathogenesis of PUD are now world. It has potent capacity of acid
gases which can lead to luminal clearly divided into three types inhibition and relief from acid related
distension and the triggering of complaints. With these benefits peo-
meal related symptoms in patients i. H.pylori associated ple are purchasing this drug from the
with IBS. For example, foods that ii. NSAID associated medicine shop. They use it randomly.
contain fructose like honey, high- iii. Miscellaneous These drugs relieve their dyspepsia.
fructose corn syrup, apples, pears, But these also produce some de-
mangoes, cherries etc should be Peptic ulcer disease clinically pre- pendencies. Besides this if a person
avoided. sent with the complaints of epigastric discontinues the drug there are some
4. Dietary fibre –Should be restricted pain. Epigastric pain is related with withdrawal effects (rebound acid-
in diarrhoea predominant IBS. On food. And it is associated with dys- ity). All these factors make persons
the other hand, dietary fibre is pepsia, heaviness and fullness of the dependent on PPI.
helpful in constipation predomi- abdomen. There is periodicity and
nant IBS. Ex – Ispaghula husk. Goal nocturnal pain. If the peptic ulcer Every medication has some ben-
is to take 10-15 gm fibre/day in disease is not properly treated they eficial effects, as well as some side
incremental doses. will produce narrowing of the lumen effects. After 30 years it is observed
5. Food allergy testing – for guidance (gastric outlet obstruction) mani- that prolonged user of PPI has many
regarding specific foods fested by vomiting. Ulcer erodes the unwanted side effects. As PPI lowers
blood vessel in the stomach wall and intragastric PH it favors opportunistic
Please tell us in brief about peptic produce hematemesis and melena. bacteria and causes diarrhea. It is
ulcer disease (PUD)? How do we also associated with some malab-
treat and prevent recurrence of PUD? PUD is associated with acid-pepsin sorption of certain nutrients like iron,
digestion. When there was no drug calcium, magnesium, zinc and other
Peptic ulcer disease means ulcera- then only treatment is neutraliza- trace elements. It has some side
tion in the stomach and duodenum tion of preformed acid in the gastric effect on kidney disease and brain
due to acid-pepsin digestion. It is a lumen. This was only treatment disease (dementia).
very common disease in gastroen- available during that period. With the
terology. It is also common in our knowledge of secretion of acid form How common is GERD in our country?
country. The point prevalence of gas- gastric mucosa, the first generation Can it lead to malignancy? How can
tric ulcer (3.8) and that of duodenal of drug is H2A receptor antagonist we prevent such complications?
ulcer disease (9). Probably it is highly like cimetidine, fametidine. Later
reported globally. In the past it was on, more potent acid suppressor Gastroesophageal reflux (GER) is a
thought that peptic ulcer disease is like PPI agents Omeprazole, Lanso- physiologic process by which gastric
of unknown aetiology. But the fact prazole came to the market. These contents move retrograde from the
that there is increased HCl secretion two groups of acid suppressors are stomach to the esophagus. GER itself
treating ulcer disease adequately. is not a disease and occurs multiple
But after the discovery of H.pylori

54 THE PHARMA WORLD

INTERVIEW

times each day without produc- meal, avoid alcohol, coffee, car- Our medical graduates and
ing symptoms or mucosal damage. bonated drinks, do some physical specialized doctors are updated in
In contrast GERD is a spectrum of exercise to maintain our body weight comparison to the western society.
disease usually producing symptoms according to height and age and They are efficient in the diagnosis
of heartburn and acid regurgitation. periodically check the mucosa of the and treatment of GI diseases like
GERD is a consequence of the failure oesophagus by upper GI endoscopy, advanced countries.
of the normal anti-reflux barrier to we can prevent complications of
protect against frequent and abnor- GERD like Barrett’s oesophagus and You see when they are working
mal amounts of refluxed material. oesophageal carcinoma. abroad they become legendary in
The prevalence of GERD is increasing that area. But due to inadequate
in Western countries due to obesity Where does Bangladesh stand infrastructure we have some defi-
epidemic. It is mainly manifested as far as prevention, diagnosis ciencies in diagnosis. We are slightly
by heartburn. In a survey in western and treatments of GI diseases lagging behind in diagnosis and
community, 25% people suffer from are concerned, compared to management of the diseases.
heartburn once a month, 12% suffer the advanced countries?
once a week and 5% suffer once a COVID-19 pandemic started in
day. There is no statistical data in our Bangladesh has been elevated to December 2019. Globally move-
country. But due to urbananisation, the status of a developing coun- ments of people are restricted. In
changes in food habit, younger gen- try recently. Some health-related the pre-covid period, people could
eration are becoming more and more parameters like MMR/INR/EPI/safe move abroad frequently for treat-
obese. They are frequently suffering drinking water/life span are better ment. But during this period people
from heartburn and GERD. than our neighboring countries. can’t go to India, Singapore and
These indices of health education, other countries. The prevalence and
The pathogenesis of GERD is food sanitation, awareness help us morbidity are always present in a
complex, resulting from an imbal- in the prevention of communica- same magnitude. Our doctors are
ance between defensive factors and ble disease like cholera, diarrhoea treating them for about one and a
the aggressive factors protecting the etc. These communicable diseases half year.
esophagus. In long run the mucosa were the major health problem in
of the oesophagus changes into Bar- our country in the recent past but The health professionals in our
rett’s oesophagus and subsequently now-a-days communicable disease country are continuously manag-
to oesophageal cancer of the lower in Bangladesh is gradually decreas- ing the health hazards with utmost
end. ing. These will reduce our health sincerity and devotion with some
expenditure significantly. exception. We need active coopera-
If we take small sized frequent tion from the policy makers in this
regard.

THE PHARMA WORLD 55



INTERVIEW

when technology is present without
expert technologists, Patients do
not get proper treatment

Prof. Dr. M. S. Arfin As an eminent Gastroenterologist In light of the recent COVID-19
Interventional Gastroenterologist of the country, would you please pandemic, do pre-existing GI
let us know about the common of disorders pose a greater risk for
Consultant pancreato-biliary and oncologic COVID-19 complications? What
Gastrointestinal, Hepatobiliary & Pan- disorders of the gastrointestinal are the GI symptoms to look
creatic Disorders Centre (GHPD) (GI) tract in our country? out for? What measures do you
recommend for its management?
Chairman The most common gastrointestinal
Bangladesh Specialized Hospital disorder, I would say, at number one This is a very pertinent question,
is Irritable Bowel Syndrome. Addition- especially in this COVID pandemic
ally, diarrhoeal diseases, acute viral situation. There are certain symp-
hepatitis and chronic viral hepatitis toms which are validly related to the
are also very common. Hepatitis A and COVID infection itself. And then there
E cause acute infection and are typi- are some symptoms or complications
cally caused by ingestion of contami- which are related to the treatment
nated food or water. These are more of COVID-19. Among the GI diseases,
common in the rural area due to scar- acute pancreatitis is a very common
city of clean drinking water and poor phenomenon in COVID situation. At
sanitation. Unhygienic street foods least 5-10% of the patients develop
in the cities also contribute to this. acute pancreatitis in COVID. In most
On the other hand, hepatitis B and C situations, these are very trivial. But,
are transmitted through exposure to at times it can be life threatening
infective blood and other body fluids. also. We have to manage these pa-
tients conservatively, by following the
Among the oncologic conditions, standard protocol for management of
hepatocellular carcinoma is very com- acute pancreatitis.
mon, especially in patients with pre-
existing liver cirrhosis and/or hepati- Another important symptom is GI
tis C patients. The stomach, pancreas bleeding. This is a common develop-
and colon are the most common sites ment, especially in ICU settings where
of GI malignancies. In biliary system, the patients are getting high doses
cholangiocarcinoma and periampul- of steroids, high doses of antiplate-
lary carcinoma are quite common. les and anticoagulants. If they have
certain pathologies in their GI sys-
Peptic ulcer disease is quite com- tem, they are more prone to develop
mon in our country, where there are bleeding from those areas. And it is
ulcers in the esophagus, stomach or very difficult to manage when the pa-
the duodenum. tients are still positive for COVID-19
virus. The process becomes difficult
So, overall, the list of diseases in because, the person who is perform-
our country concerning the GI system ing and the team involved in the pro-
is not much different from the other cedure are also exposed to a greater
countries in the world. There are some risk of contracting COVID. We have to
diseases which are more prevalent in take very very strong measures to pre-
our country like the diarrheal diseases vent transmission of the disease to the
and the peptic ulcer disease complex. working team. In most situations we
On the other hand, prevalence of dis- try to wait until the patient becomes
eases like IBS and GI malignancies are
more or less the same worldwide.

THE PHARMA WORLD 57

INTERVIEW

COVID negative and then we intervene. show similar symptoms as IBS. But the like biscuits that can also trigger the
If any drugs are involved in his, we try difference is, if we examine the GI sys- symptoms of IBS. Then, any infection,
to withdraw the drug if possible at all. tem, we don’t find anything significant especially GI infections such as infec-
in case of IBS. So, if the patient has tious diarrhea and dysentery cause
There are certain other situations symptoms, and there is nothing found persistent symptoms in IBS-D. Leafy
where COVID is more dangerous to upon examination, then it is IBS. vegetable, dal, especially masoor dal,
the patients if they have chronic GI raw vegetables like salad, atta, espe-
diseases like liver cirrhosis, chronic Depending on the predominant cially the red atta, any atta with bran
pancreatitis or acute pancreatitis. In symptoms, IBS is categorised in dif- can exacerbate IBS-D symptoms. Each
our hospital, I have got a lot of cas- ferent subgroups. These include IBS- individual can identify the foods that
es where patients came with acute D (diarrhea predominant), IBS-C (con- may trigger their symptoms them-
pancreatitis, and upon screening for stipation predominant) and IBS-M selves and avoid those foods.
COVID-19, around 30% were found to (mixed/ alternate type). There is an-
be positive. Then, it becomes difficult other group of IBS patients who has Food is important, but not the only
to treat all those cases. These are not abdominal pain, irrespective of the factor. Stress is also likely to increase
directly related to COVID, but may be pattern of bowel motion, categorised symptoms in IBS-D or IBS-P, the pain
secondarily infected with COVID after- as pain predominant IBS. IBS-D is as- predominant IBS. Any conditions
wards or they may be infected earlier sociated with frequent bowel move- which break the mental peace, famil-
and then developed pancreatitis. ment, 4-5 motions a day- mostly loose ial disharmony, sexual disharmony
or watery, without losing significant and menstrual disharmony in women
Then we have liver cirrhosis in im- weight, without any significant labo- also trigger symptoms in IBS-D.
munocompromised situation; when ratory or investigatory finding in the
these patients get infected, the mor- GI system. Then we have IBS-C where So, IBS is such a complex disease
bidity and mortality becomes much patients experience infrequent bowel that you cannot propose any formula
higher. This is also true for any other movements (every third or fourth to prevent it. Avoiding the foods that
chronic disease in immunocompro- day), abdominal discomfort, bloating trigger the symptoms may help im-
mised patients- any infection comes and incomplete bowel action, also, prove the condition. Exercise, espe-
with a greater risk of morbidity and without any significant finding upon cially pelvic exercises may help IBS-D
mortality. As for management, most of investigation, even in the colon. The patients to improve urgency in def-
the times, it is conservative. In acute IBS-M patients suffer from alternating ecation. Stress can also be minimized
situations where the GI related proce- diarrhea and constipation. with exercise. Mood elevating drugs
dures become a life-saving one, we do may be prescribed.
it by taking extraordinary preventive These are simple classifications.
measures. So, when there is no way to However, after other conditions or dis- Please tell us in brief about peptic
treat the patients conservatively, we eases have been ruled out, there are ulcer disease (PUD). How do we treat
go for endoscopic intervention. international criteria we follow to diag- and prevent recurrence of PUD?
nose and classify IBS such as the Rome
What are the trigger factors criteria. The gastroenterologists all PUD is also a multifactorial dis-
and symptoms for Irritable over the world and the authors of gas- ease. It was previously thought, es-
Bowel Syndrome (IBS)? Is it troenterology have come up with these pecially in our country, that it is re-
preventable? What changes in criteria to diagnose, classify and treat lated to hot spices or high fibre diet.
diet can help the patients? IBS based on the clinical symptoms. It was a common disease, even when
we were young gastroenterologists.
IBS is a very complex disease. The Since this disease is classified into Two Australian gastroenterologists
name itself is “irritable”, which means quite a good number of varieties with have discovered the role of Helicobac-
it irritates. It is a multi-factorial dis- diversified symptoms, that’s why you ter Pylori in peptic ulcer. Peptic ulcer
ease. There is not a single factor which cannot blame a single food or a single means presence of ulcers in esopha-
is solely responsible for the symptoms cause for triggering the disease. For ex- gus, lower third of the esophagus, the
of this disease. This diagnosis is done ample, IBS-C is not at all related to diet. stomach itself, then the duodenum
by exclusion method. It has no distinct or the jejunum. Ulcers in these sites
symptoms which we can consider as Certain diets which causes gas are called peptic ulcers. Mostly they
gold standard symptoms by which can increase the discomfort, espe- are related to Helicobacter Pylori.
we can make a concrete diagnosis of cially milk products, certain vegetable There are certain drugs, especially
irritable bowel syndrome. There are should be avoided. Dairy products the pain killers, NSAIDs, aspirin, cal-
certain symptoms which predict that can cause diarrhoea and other symp- cium tablets, potassium tablets etc.,
it can be IBS. But, we have to exclude toms in IBS-C or D, similar to the pa- which can cause peptic ulcers. Pre-
other diseases which are likely to tients with lactose intolerance. Milk or vention of H. Pylori is almost impos-
milk products, even milk added foods

58 THE PHARMA WORLD

INTERVIEW

sible, as these bacteria are extremely believed to be ‘gastric’ and they think atic duct system. For example, surgical
prevalent in our environment and we all these symptoms are due to peptic instruments can be passed through
can hardly avoid entry of H. Pylori in ulcers. But there is nothing called gas- the endoscope, allowing us to remove
our body. This is mostly transmitted tric in the textbook of medicine. Gas- a stone in a bile duct or insert a bal-
through water. It is a waterborne dis- tric means something related to the loon or stent to dilate the bile duct to
ease. Before the 2nd World War, PUD stomach. So, what the people refer bypass a blockage in the duct that is
was more frequent in Europe and the to as “gas er oushudh”, in reality, are caused by a stone, scarring, or cancer.
western countries, due to poor sanita- the acid lowering agents e.g. the PPIs. This can also provide some sympto-
tion and standards of living. After the The PPIs also reduce the symptoms, matic relief to the patients. In case of
World War II, PUD has become a minor which encourages the patients to take acute pancreatitis, we can introduce a
disease due to the provision of safe the medicine. Even in the US there are tube in the pancreatic duct to be with-
water and improvements in sanitation some PPIs which are available over drawn after 6-8 months, allowing itself
and personal hygiene. However this is the counter. This is not a practice in to reshape the pancreatic duct. Thus,
not the case in the third world coun- our country only, but it is practiced all complications of the chronic pancrea-
tries, including our country. Sanitation over the world. So, PPIs are generally titis can be reduced. So, we can per-
is still poor, contamination of water is self-prescribed by the patients, and form an array of curative and palliative
widespread, bacterial contamination some physicians or gastroenterolo- procedures through ERCP and improve
is very common especially with H. Py- gists also prescribe them as preven- the quality of life of the patients.
lori, so, prevention of PUD is next to tion of side effects of other drugs.
impossible. But, we can eradicate H. Those patients may become habitu- Where does Bangladesh stand
Pylori from the body, once it’s detect- ated in using PPIs for a long time. As as far as prevention, diagnosis
ed through various tests, with a com- a result, they may have interstitial and treatments of GI diseases
bination of antibiotics, given together nephritis. There are some PPIs which are concerned, compared to
or in a sequence as chronic sequential can cause hyperplastic polyp in the the advanced countries?
antibiotic therapy. After eradicating stomach which may bleed and in rare
the bacteria, we need to stabilise the occasions can even progress to ma- Actually, all the facilities of GI in-
stomach and the mucus membrane to lignancy. So, the use of drugs should vestigation and treatment modali-
prevent the reinvasion of H. Pylori. In be rational, especially the PPIs. The ties other than a few exceptions, are
recent days, we are giving probiotics General practitioners play a very im- available in this country, but we are in
to prevent resurgence of the bacteria portant role in such situations. GPs need of expert manpower. Whatever
after the eradication by the antibiotic should curtail the dose or discontinue is available in the developed world,
therapy. Good dietary and drinking PPIs once their intended purpose is is available here , to a limited extent.
habit may help to prevent ulcers. fulfilled. Counseling the patients and
giving them right instructions would We have expert gastroenterolo-
Being available over-the counter, help avoid these unwanted side ef- gists, whose skills are at par with the
patients now-a-days are self- fects. There should be government advanced countries, but the number
prescribing and overusing anti- regulations on selling of these drugs. is not adequate for a country like
ulcerant drugs i.e. PPIs. What are the Bangladesh, where the population is
consequences of such irrational use? As an expert in around 180 million. As long as tech-
Endoscopic Retrograde nology is concerned we are there,
Number one thing is that in our Cholangiopancreatography if we are talking about the services
country, people saying that anything (ERCP), please tell us about provided to the patients, we are half-
related to the upper abdomen is pep- the procedure. For which GI way. There are many such incidences
tic ulcer and they just call it ‘gastric’. conditions can ERCP be used? where the patients who do not get
And if you interview the patients, sev- proper treatment, follow up their
en or eight out of 10 would give differ- Initially, until the early nineties, this treatment, or are provided partial
ent symptoms for what they call ‘gas- procedure was used to diagnose any treatment, when they’re not in good
tric’. Some would say that they cannot disease of the bile duct, the pancreatic hands. This is a common phenom-
let out gas or they have gas built up duct, or the pancreas itself. But with enon when technology is present
or bloating, some would complain the advent of the MRI and MRCP (Mag- without expert technologists. This is
of pain after eating, some complain netic resonance cholangiopancreatog- the problem that is prevailing in our
of burning sensation in the chest raphy), the diagnostic value of ERCP country at this moment. But, in course
and some patients even complain of has come down to almost zero. Now of time, InshaAllah, as we’re getting
headaches. So, there are these vari- ERCP is used for the treatment pur- more and more trainings, we’ll have
ety of symptoms what the patients poses of the bile duct, and the pancre- more experts in the future to benefit
our people.

THE PHARMA WORLD 59



INTERVIEW

Effective management of recurrent
PUD relies on Identification and
modification of reliable risk factors

Prof. Dr. Md. Ashraful Islam The most common gastrointestinal in life style and food adulteration.
Specialist in Medicine, Gastro-intesti- diseases in Bangladesh are: Common GI malignancy are:
nal & Liver Diseases • Gastroesophageal Reflux Disease • Gastric carcinoma
Ex-Head, Dept. of Gastroenterology • Esophageal carcinoma
Dhaka Medical College & Hospital (GERD) • Pancreatic carcinoma
• Peptic ulcer disease • Colon cancer
As an eminent Gastroenterologist • Non ulcer dyspepsia • Cholangiocarcinoma
of the country, would you please • Dysphagia • Primary and secondary cancer of
let us know about the common • Inflammatory bowel disease
Gastrointestinal, pancreatico-biliary • Diarrhoeal disorders the liver
and liver diseases in our country? • Chronic constipation • Gastrointestinal stromal tumor
• Haemorrhoids
The gastrointestinal system is an • Irritable bowel syndrome (GIST)
extensive and complex system that The liver is responsible for many
breaks down ingested food materials critical functions within the body and In light of the recent COVID-19
in order to absorb water and extracts when it is injured, the loss of those pandemic, does pre-existing GI
nutrients. It extends from mouth to functions can cause significant dam- disorders pose a greater risk for
anus and included the side organs age to the body functions. The com- COVID-19 complications? What
like the Liver, the Pancreas and the mon Liver disease are: are the GI symptoms to look
Gall bladder. • Acute viral hepatitis out for? What measure do you
• Chronic viral hepatitis recommend for its management?
• Cirrhosis of liver
• Non Alcoholic Fatty Liver Disease Any part of the digestive system
may be affected by the SARS-COV-2
(NAFLD) virus and those with pre-existing
• Malignant tumor of the Liver liver disease, like chronic hepatitis or
• Hepatic amoebiasis cirrhosis are of higher risk of death
than people without pre-existing
Most of the gastrointestinal diseases liver disease. Patients with inflam-
are preventable and if detected ear- matory bowel disease with COVID-19
lier, it is easy to treat. infection may cause worsening of
the symptoms. Those are on im-
The pancreatico-biliary system in- munosuppressant therapy has an
cludes the pancreas, the gall bladder increased risk of morbidity.
and the bile ducts. Common diseases
of this systems are: These patients should take all
• Cholelithiasis preventive measures for COVID-19
• Cholecystitis infection and vaccination should be
• Choledocholithiasis done on priority basis. If infected
• Acute and chronic pancreatitis should be hospitalized and special
• Cholangiocarcinoma care should be given for the primary
• Gall bladder malignancy disease. Early detection and proper
• Pancreatic malignant tumor treatment should be ensured.

Oncologic disorders of GIT in Bangla- What are the trigger factors
desh is gradually rising due to im- and symptoms for Irritable
provement in socioeconomic condi- Bowel Syndrome (IBS)? Is it
tion, changes in food habits, changes preventable? What changes in
diet can help the patients?

THE PHARMA WORLD 61

INTERVIEW

Irritable Bowel Syndrome (IBS) is a peptic ulcer, if possible stop NSAID ated with GERD symptoms, including
functional GI disorder characterized and treat with H2 receptor blockers dietary factors, alcohol consumption,
by abdominal pain, altered bowel or proton pump inhibitors. smoking, NSAID and obesity.
habits in the absence of a specific
pathology. It is not a preventable Effective management of recurrent Most symptoms of GERD can be
disease but with proper self care may PUD relies on identification and modi- managed with a combination of
help ease the symptoms. The symp- fication of reliable risk factors. Ensure medications and changes in life
toms of IBS are variable but usually proper Helicobacter Pylori eradica- style. Medications that can be used
present for a long time. The most tion regimen on local antibacterial to neutralize acid of the stomach
common symptoms include, abdomi- resistance pattern. Long term proton are antacids, reduced production of
nal pain, cramping or bloating that pump inhibitor medication may be hydrochloric acid with H2-receptor
is related to passage of stool, altered necessary to prevent recurrence of antagonist or proton pump in-
bowel habits – constipation or diar- Helicobacter Pylori negative ulcer, hibitors. Proton pump inhibitors are
rhea and increased abdominal gas or NSAID negative ulcer and for patients better than H2-receptor antagonist.
mucous in the stool. who require NSAID or asprin as main- Refractory GERD should be treated
tenance therapy. with surgery.
Symptoms of IBS can be triggered
by certain foods such as wheat, dairy Being available over-the counter, Where does Bangladesh stand
products, citrus fruits, beans, cab- patients now a days are self as far as prevention, diagnosis
bage and carbonated beverages. prescribing and overusing anti- and treatment of GI diseases
Those foods which aggravate the ulcerant drugs i.e. PPIs. What is concerned, compared to
symptoms should be avoided. True are the consequences of such the advanced countries?
food allergy rarely causes IBS. other irrational use in long term?
factors include stress, severe bouts Bangladesh is a small country but
of diarrhea caused by bacteria or Self-medication is a global phe- the population density is very high
virus and certain drugs. nomenon but it causes serious and the number of patients suffering
health hazards such as adverse reac- from GI disease is also very high than
Please tell us in brief about peptic tions and prolonged suffering. other diseases. The socioeconomic
ulcer disease (PUD)? How do we treat condition is poor in our country than
and prevent recurrence of PUD? In our country it is common prac- western countries and the number
tice of self-prescribing and overuse of of gastroenterologists is also less
Peptic ulcer disease is a condition in anti-ulcer medicine. The consequence compared to the western countries.
which sores or ulcer develop in the of irrational long term use of PPI are, We are still running behind advanced
lining mucosa of the stomach, duo- pneumonia, clostridium difficile diar- world in prevention, diagnosis and
denum or lower end of oesophagus. rhea, hypomagnesaemia, vitamin B12 treatment of GI diseases.
Normally a thick layer of mucous deficiency, chronic kidney disease,
protect the stomach lining from the risk of fracture due to osteoporosis, IBS Our socioeconomic condition is
effect of its digestive juices, particu- like symptoms, dementia etc. gradually improving and our patients
larly the hydrochloric acid. Reduction are becoming more aware of their
of the protective mechanism allows How common is GERD in our country? health problems. Young gastroen-
stomach to be damaged by the di- Can it lead to malignancy? How can terologists are coming out every
gestive juices. The causes of peptic we prevent such complications? year from different medical colleges,
ulcer disease are, Helicobacter Pylori which, previously were only from
bacteria, pain reliving NSAID medica- Gastroesophageal Reflux Disease BSMMU and number of gastroenter-
tions and Zollinger Ellison Syndrome. (GERD) is a global disease and the ologists are rapidly increasing. Our
There are some risk factors for peptic prevalence is gradually increasing. government took measures for vac-
ulcer disease like smoking, drinking It is less common in Asian countries cination against hepatitis B virus and
alcohol, associated liver or kidney in camparison to western world. The screening blood donors for hepatitis
disease and psychological stress. prevalence differ from rural to urban B and C viruses. Government has
areas. The prevalence of GERD in ru- provided modern endoscopic equip-
Treatment of peptic ulcer var- ral areas of Bangladesh is about 6.8% ments for diagnosis and treatment
ies depending on the etiology and but, this figure is slightly higher in of GI diseases. For last two decades
clinical presentation. H.pylori related urban population. there were great improvements in
peptic ulcer should be treated with the field of gastroenterology in both
empiric triple therapy after endo- It can lead to Barrett’s esophagus government and private sector of
scopic diagnosis. In NSAID related and esophageal carcinoma which is Bangladesh.
difficult to treat. There are many fac-
tors which are thought to be associ-

62 THE PHARMA WORLD

Worth Knowing About

link between Crohn’s disease and fatigue A person should also wish to focus on adding
more vitamin B12, iron and folates, or folic acid, to
IBD  increases a person’s risk of developing  chronic their diet.  Research suggests  that deficiencies of
fatigue syndrome (CFA). CFA is a long-term illness that these nutrients can also cause extreme fatigue.
can cause pain and extreme fatigue. This fatigue can
occur during flare-ups of symptoms and periods of Treatments targeting the liver
remission. One  2020 reviews states that fatigue af- could treat type 2 diabetes
fects almost 50% of people with IBD. According to
the  Crohn’s and Colitis Foundation, it can be even Researchers have investigated the link between fatty
more common, affecting nearly 80% of people with liver disease and key markers of type 2 diabetes in
IBD during a flare-up and 50% of those in remission.​​ mice. The researchers say that the treatment pathway
may exclusively work among people with obesity.
Symptoms of CFA include : Previous research has shown that type 2 diabetes is
l a reduced ability to perform tasks strongly linked to overweight  and fatty liver disease,
l the feeling of a “crash” after physical or men- which involves storing excess fat in the liver. Accord-
ing to the Centers for Disease Control and Prevention
tal exertion (CDC), 89%  of people with diabetes are overweight.
l sleep disorders, including vivid dreaming, Recently, researchers found that insulin sensitivity
can be restored within days of reducing excess pro-
restless legs, muscle spasms, and sleep apnea duction of the  neurotransmitter  GABA in the liver
l dizziness and that long-term treatment may lead to decreased
l issues with memory appetite and weight loss. From studying mice, the
l aches and joint pains researchers  first found  that obesity-induced fatty
liver disease increases the production of GABA in the
There are several things that a person with Crohn’s liver. They then found that increased GABA signaling
disease may experience that can cause fatigue. from the liver affects glucose homeostasis. Because
These include: earlier research found that an enzyme called GABA
transaminase (GABA-T) is key for producing GABA in
l Inflammation:  When inflammation occurs in the liver, the team suspected that targeting GABA-T
the digestive tract, the body produces chemi- to produce less GABA in the liver may reduce insulin
cal signals in response to the inflammation. resistance and treat type 2 diabetes.
These chemical signals  can cause  tiredness
and a lack of energy. They can also contribute To test their hypothesis, the researchers first
to a feeling of fatigue. treated mouse models of type 2 diabetes with drugs
that inhibit GABA-T activity. These drugs are known
l Anemia:  Approximately  one-third   of people as ethanol-amine-O-sulfate (EOS) and vigabatrin.
with IBD have anemia. This means that their
red blood cells cannot transport enough oxy- The team’s second means of testing its hypothe-
gen to their body’s tissues, which can make a sis involved a genetic treatment known as antisense
person experience tiredness and weakness. oligonucleotide (ASO). This works by binding small
pieces of DNA or RNA to molecules of RNA to stop
l Side effects of medications:  Certain Crohn’s it from making certain proteins. In this case, ASO
disease medications can also cause fatigue. worked by disabling GABA-T expression in the liver.
This includes steroids that can interfere
with a person’s sleep patterns, while immu- Both treatment methods reduced GABA-T activ-
nomodulators, such as methotrexate and ity and improved insulin sensitivity within days.
6-MP, can also lead to fatigue. Mice given ASO and EOS drugs also lost 20% of their
body mass after 7 weeks of beginning treatment.
l Anxiety:  People with Crohn’s disease have
an increased risk  of experiencing anxiety, of The researchers then examined liver samples
which fatigue is a symptom. taken from 19 people with obesity during bariatric
surgery procedures. They analyzed gene expression
l Prolonged poor sleep:  Individuals with in the liver tissue and found that those with insulin
Crohn’s disease may experience poor sleep. resistance had high levels of expression for genes
This may be because certain symptoms, such related to GABA production and activity.
as stomach pain, can interrupt their sleep. If
a person experiences reduced quality sleep This means that the findings in the mouse mod-
for a number of nights, it could lead to them els might translate to humans.
developing fatigue.

THE PHARMA WORLD 63



INTERVIEW

Viral hepatitis is the greatest concern
right now because of the burden of
illness and death they cause

Prof. Dr. Shahinul Alam As an eminent Hepatologist of nificant liver injury in CLD patients,
Professor the country, would you please let decompensated one fifth of cirrhosis,
Dept. of Hepatology us know about the prevalence of and significantly worsened the clini-
BSMMU, Dhaka liver diseases in our country? cal status of the patients. In addition,
fatty liver patients with metabolic
At least one third of our popula- syndromes such as diabetes, dyslipi-
tion is suffering from liver disease. demia, hypertension and obesity were
So, around 5 crores are suffering from found to be more vulnerable.
liver diseases. Among them 1 crore is
suffering from hepatitis C and hepa- Considering this unprecedented
titis B viruses. Approximately 4.5 to 5 phenomenon, various global liver so-
crores have fatty liver. Liver disease cieties have come up with guidelines
is the 8th leading cause of mortality on vaccination in this population and
in our country. Around 37% to 69% of in Bangladesh also, we recommend
them are suffering from either cirrho- high prioritisation of COVID-19 vacci-
sis or chronic liver disease (CLD). 10% nation in patients with liver diseases.
to 13.2% of all the patients presented As liver patients with metabolic syn-
to the medicine departments of our drome are at high risk of mortality
medical colleges were diagnosed with from SARS-Cov-2 infection, they are
liver diseases. If we categorise liver prioritised over others for hospitaliza-
diseases according to their severity tion and early treatment, even during
and seriousness, number one is liver mild cases of COVID. Another thing we
cancer, then cirrhosis, then chronic have to remember is that many of the
hepatitis B. In recent years, fatty liv- medicines used for treatment of COV-
er diseases are on increasing trend, ID-19 are hepatotoxic and has wide ar-
replacing hepatitis C virus infection ray of adverse effects on the liver. So,
as one of the leading liver disorders. caution is a must during the treatment
Today, mortality due to liver diseases and selection of medications.
account for around 3% of  all deaths
worldwide. Please tell us, in brief, about the
prevalence of Viral Hepatitis
In light of the recent COVID-19 in Bangladesh? What are your
pandemic, does pre-existing liver suggestions to create awareness
disease (chronic liver disease, among the common people
cirrhosis, or related complications) about viral Hepatitis?
pose a greater risk for COVID-19
complications? What measures do Viral hepatitis is the greatest con-
you recommend for its management? cern right now because of the bur-
den of illness and death they cause
A collaborative study among 26 and the potential for outbreaks and
countries including Bangladesh, pub- epidemic spread. Interestingly, viral
lished in journal ‘Hepatology Interna- hepatitis is preventable. There are 5
tional’, showed that pre-existing CLD main hepatitis viruses, referred to as
is associated with poor outcome in types A, B, C, D and E. Types B and C
patients with SARS CoV2 infection. The lead to chronic disease in hundreds
study, called APCOLIS, demonstrated of millions of people and, together,
that SARS-Cov-2 infection caused sig- are the most common cause of liver
cirrhosis and cancer. Types A and E

THE PHARMA WORLD 65

INTERVIEW

cause acute hepatitis and are typi- Thousands of hepatitis patients are getting medicines free
cally spread by ingestion of contami- of cost, by government initiative, but the number of patients
nated food or water i.e. street foods who require the treatment is much higher. If we could
like fuchka/chotpoti or unclean water. decrease the taxation on the raw materials for the medicines,
While Hepatitis A vaccines are avail- we could lower the price of those medicine by 16%.
able for children, but no vaccine is still
available here for E viruses. Hepatitis areas of the country. Histories of sur- sequences like liver cirrhosis and liver
B, C and D usually occur as a result of gery, accidents or visit to causal or cancer, but lifestyle could help people
parenteral contact with infected body emergency departments are associ- easily avoid the problem by taking
fluids. Common modes of transmis- ated with Hepatitis C infection. To pre- healthy diet and exercise. Previously,
sion for these viruses include receipt vent this, we need proper sterilization the main risk factors for cirrhosis were
of contaminated blood or blood prod- practice for surgical instrument in all alcohol, hepatitis B, and hepatitis C.
ucts, invasive medical or dental pro- public and private hospitals. Global Nowadays, fatty liver has become the
cedures using contaminated equip- hepatitis goals under SDG’s should most common contributor to cirrho-
ment. Commonest mode of Hepatitis be strongly executed and integrated sis. So, we should prepare to tackle
B virus transmission is mother to child into our national policies to eliminate the challenge of fatty liver, especially
in Bangladesh. In our country around hepatitis. in our country where every age group
85 Lacs and 15 Lacs of the people are is affected, from children to adoles-
suffering from Hepatitis B and Hepa- Is there any cross interaction cents to the elderlies. The pandemic
titis C respectively. The prevalence of between covid vaccine and hepatitis has taken a toll on our children in par-
Hepatitis B has come down to 5.2% B vaccine? How long should a ticular, as they are staying home, they
due to vaccination. Males are the Covid vaccinated person wait till are not playing outside. Our schools
majority with projected number of 57 getting the Hepatitis B vaccine? also don’t encourage sports anymore.
Lacs suffering from Hepatitis B. Pro- The children are staying in front of the
jected female and children popula- It’s not currently recommended to screen all day. In addition, our diet
tion suffering from Hepatitis B are 28 get the COVID-19 vaccine around the also changed a lot. The urban popula-
Lacs and 4 Lacs respectively. 25 Lacs same time with the other vaccina- tion is more inclined to having west-
young people and 18 Lacs female of tions.  Both hep B and COVID-19 vac- ern style greasy foods and drinks with
childbearing age carry Hepatitis B vi- cines are equally important, however high sugar contents which contributes
rus in our country. As for Hepatitis C, we recommend spacing the vaccines greatly to fatty liver. If we look at the
the prevalence is around 0.2 % but it between duration of one month. rural area, the physical activity among
is much more in healthcare workers. women and men has also decreased
To eliminate viral hepatitis, the first How common is fatty liver disease considerably compared to a decade
step we should take is to build aware- in our country? What are the risk ago. All these are leading to obesity
ness about viral hepatitis. Screening is factors? What lifestyle changes do among our population. One study has
crucial. It is estimated that a nation- you suggest to fatty liver patients? shown the prevalence of fatty liver
wide screening campaign would not disease in Bangladesh has increased
cost more than a thousand crores of Fatty liver is the most widely dis- to 33.8%.Females living in the rural ar-
taka. So, if our government could un- cussed topic in medicine worldwide. eas and midlife adults had the highest
dertake such a project to diagnose The incidence and  prevalence  of prevalence. 10%-20% of all cirrhosis
hepatitis B and C infections among fatty liver are rapidly rising with the cases worldwide develop from nonal-
our population and provide treatment changes in our lifestyle and diet pat- coholic steatohepatitis (NASH) leading
on priority basis, these diseases could terns. Sedentary lifestyle and decrease to “cryptogenic” cirrhosis which can
be prevented successfully. Women of in physical activity have affected both also result in end-stage liver disease
childbearing age should be vaccinated the urban and rural population. Our or hepatocellular carcinoma. Alarm-
on priority basis to prevent viral hepa- children are also staying home, with ingly, in our country it is much higher;
titis in the next generation. Our goal little physical activity. So, Fatty liver is at 12% to 25%. Among the risk factors
is to eliminate hepatitis B by the year becoming a huge challenge to face in there are obesity, Type 2  diabetes  ,
2030. The World Health Organization the future. Fatty liver has severe con- metabolic syndrome  (insulin resist-
has stated that Bangladesh is on the
right track to eliminate Hepatitis B vi-
rus. On the other hand, study shows
prevalence of Hepatitis C virus ranges
from 0.2 to 1% in urban and sub-urban

66 THE PHARMA WORLD

INTERVIEW

ance, high blood pressure, high cho- equipment and availability of PLEX in Same goes for radiofrequency abla-
lesterol and high triglyceride levels), government hospitals would surely tion and chemoembolisation. So, we
high cholesterol and high levels of help many patients. must create policies and programmes
triglycerides. But this disease is very which will educate the patients to
much preventable. So, we should act Please tell us in brief about take action to prevent liver cancer and
now. A complete improvement of life- Hepatocellular carcinoma encourage them to go for screening
style should be a top priority. Europe- (HCC)and its treatment? for early diagnosis. For screening, all
an Liver Association has published a we need is ultrasonogram and some
policy statement which recommends Three main causes for developing blood tests like liver function test
public health policies to restrict ad- liver cancer are Hepatitis C, Hepati- and Alpha-fetoprotein, which, if made
vertising and marketing of industri- tis B and fatty liver. Risk for develop- available free of cost at zilla/upazilla
ally processed foods high in trans-fat, ing  liver cancer can be reduced by level, could save so many lives.
sugar and salt. They also recommend preventing these diseases. We can
health education programmes which prevent fatty liver by following healthy Where does Bangladesh stand as far
emphasise the benefits of a Mediter- lifestyle measures like exercising reg- as diagnosis and treatment of liver
ranean diet, encourage regular physi- ularly and eating a healthy diet. Also, diseases are concerned, compared
cal activity and create infrastructure we need to create a nationwide move- to the advanced countries?
like fields, tracks and bicycle lane to ment against fatty liver. We can avoid
improve opportunities for exercise infection with hepatitis B virus by get- All the medicines for the treatment
and reverse sedentary life styles. ting vaccinated. The  Hepatitis B vac- of hepatitis B and C are available in our
Some European countries even in- cine  is recommended for all infants country and that too at the lowest cost
troduced Fat-Tax upon fattening food at birth and for adults who may be at in the world. Even then, it is beyond
and beverages. We also need to take increased risk. There is no vaccination purchasing power of most of our pa-
prompt decisions and create similar for hepatitis C at this time, so it’s cru- tients. Although thousands of hepatitis
programmes/ policies at personal, so- cial to get regular screening for hepa- patients are getting medicines free of
cial, local and national level to combat titis C for high risk population. In a cost, by government initiative, but the
the emerging wave of the disease. country like ours, where the budget in number of patients who require the
health sector is not more than 5%, we treatment is much higher. If we could
What is the role of Plasma exchange should prioritise more on prevention decrease the taxation on the raw ma-
(PLEX) in Acute on chronic liver than treatment. In our country, 70%- terials for the medicines, we could
failure (ACLF)? What can be done to 80% of the treatment cost is borne by lower the price of those medicines by
reduce the mortality rate in ACLF? the patients and around 50 to 60 Lacs 16%.So, more patients can be accom-
of patients fall into poverty every year modated under the special govern-
ACLF is a very dangerous disease to manage that treatment bill. So, it’s ment programme. The social service-
with very high mortality rate. ACLF is a must to put more emphasis on pre- oriented initiative by the government
the acute deterioration of liver func- vention of hepatocellular carcinoma. also covers a small number of cirrho-
tion in patients with underlying liver Early diagnosis is very important. The sis patients. But the number should
disease i.e. fatty liver, chronic liver dis- early diagnosis is a big challenge due be increased. As for the advanced or
ease, cirrhosis or viral hepatitis B due to the absence of symptoms in pa- sophisticated procedures like liver
to a superimposed liver injury or hepa- tients with early disease. If diagnosed transplantation, we have the technol-
titis E infection. Consequences of ACLF early, we can do surgery or liver trans- ogy and expertise, but the availability
include acute decompensation, liver plant to save the patient. But when it is centralised. The problem is that the
failure and high short-term mortality. is diagnosed at an advanced or termi- services have not been disseminated
When ACLF can’t be reversed, the only nal stage, there is nothing much we throughout the country equally. We
treatment is a liver transplant. Plasma can do to save the patients. Options need a liver institution in Dhaka as well
exchange is a recommended bridging we have at this stage are surgery, as liver centres at district level and a
therapy to liver transplantation and liver transplant, chemoembolization liver OPD at Upazilla level. This will help
also has better transplant free surviv- (TACE), immunomodulators, radiofre- us distribute the huge load of patients,
al. Not many hospitals have the com- quency ablation etc. which are very thereby easing the patients’ sufferings
modity in our country. The main ob- expensive, while the chance of surviv- and save them the transport cost. With
stacle which we face in Bangladesh for al remains very low. For example, im- the help of the government, we can
utilising PLEX is, the high price of the munotherapy costs several Lacs taka, lead our liver care to the international
chemicals, medicines and equipment. while after the therapy, the patients standard. Prevention programme must
Tax reduction on the chemicals and survive only for a few more months. be adopted at primary care level.

THE PHARMA WORLD 67

GLEANINGS FROM THE LOCAL PRESS

Pandemic a boon for some pharma, bane for many

​Giant drug-makers report 30% growth in sales while
smaller firms log businesses fell by up to 50%

ONLY PHARMA GIANTS RAKE IN COVID SALES

Year-on-year drug sales spiralled 17.21%

during pandemic

Sales surged by Rose to

TK4,000CR TK27,000CR

269 ACTIVE DRUG-MAKERS IN COUNTRY

20-25 Others
witnessed
companies lead sales slump
the market

SMALLER PHARMAS FARED BADLY WITH

Their less Pandemic-led Disrupted
popular raw material marketing chain
brands crunch

Only leading pharmaceutical journey in 1996, registered a 12% fall in pharmas put up an impressive perfor-
companies could translate sales and saw its annual profit plunge mance in the pandemic time.
pandemic blues into higher by 50% in the first nine months of
sales, while most small ones wit- the fiscal 2020-21, according to Dhaka SM Shafiuzzaman, secretary general
nessed a slump in their businesses Stock Exchange data. of the Bangladesh Association of Phar-
owing to being lesser-known brands, maceutical Industries, said suspension
virus-led raw material crunch and a Sector people said sales of pre- of private practice and restriction on
jeopardised marketing chain. scription-based drugs plummeted marketing representatives’ movement
as most doctors suspended private deterred the smaller firms from retain-
With drug businesses surging by practice because of infection fears in ing their market positions.
more than 17% in the coronavirus the pandemic.
pandemic, the country’s pharma sec- “As people bought medicines of
tor had witnessed drug sales rise by During the prolonged period marked familiar brands over the counter,
Tk4,000 crore to Tk27,000 crore from by a series of lockdowns, people would companies that were already in the
May 2020 to March 2021, according to turn up at drug stores to buy medicines leading position before the pandemic
the US-based health information tech- that go by popular brand names. Lead- fared better,” he noted.
nology and clinical research firm IQVIA. ing drug-makers exploited the surge
in the over-the-counter sales – that Tingku Ranjan Sarker, company
Take for Sylhet-based Silco Pharma resulted in even 30% sales growth for secretary of Silco Pharma, echoed
that had been registering more than the pharma giants while sales of the Shafiuzzaman on promotional mar-
20% steady growth for three years be- smaller firms sank to around 50% com- keting. On top of this, he said the
fore Covid-19 broke out in Bangladesh pared to regular times. pandemic jeopardised the supply of
in March last year. active pharmaceutical ingredients.
There are 269 drug-makers in
The company, which started the Bangladesh, of which only 20-25 big The sales of Barishal-based Rephco
Pharmaceuticals – a drug-maker that

68 THE PHARMA WORLD

GLEANINGS FROM THE LOCAL PRESS

has been in the market for more than  Globally, the prevalence of hepatitis B virus in
50 years – dropped to Tk50 crore in children under 5 years is now below 1 percent,
2020 from previous year’s Tk80 crore. meaning the SDG target has already been achieved.

According to the IQVIA, as much as  More than 9.4 million people globally have received
71% of the drugs at the end of March treatment for hepatitis C, a 9-fold increase since 2015.
this year were manufactured by top
10 pharma giants in Bangladesh. The  The statistics of childhood cancer is alarming and
market share of these firms amount- more than 300,000 children ages birth to 19 years are
ed to below 69% even a year ago. diagnosed with cancer around the world every year.

The companies expanded their  Among childhood cancer 5-year survival in low
market by ramping up the production income countries as low as 10% while that in
of Covid treating drugs such as rem- developed countries like USA and UK as high as
desivir, ivermectin and azithromycin. 80%.

Officials at the companies said they  More than 1 in 10 under five deaths in Bangladesh is
have boosted up the supply and sales because of pneumonia.
of food supplements as the pandemic
has spiralled the demand for miner-  One in every four adults aged over 18 years are
als and vitamins such as vitamin C suffering from hypertension while one in every 10
and vitamin D – that are believed to adults have diabetes, according to a survey conducted
strengthen immune defence against in the Bangladesh.
coronavirus infection.
 There will be 30 million hypertensive cases in 2020,
The officials said they focused on re- about 38 million in 2030, about 46 million in 2040
taining the confidence of doctors, and and about 52 million in 2050 in Bangladesh.
the management of the newly emerged
Covid drug market – that eventually led  Some 20 million people are suffering from kidney-
them to better sales performance. related diseases in the country and some 40,000
people develop kidney failure every year in
Take for leading drug-maker Square Bangladesh.
Pharmaceuticals with a 17% market
share. From April 2020 to March 2021,  Under-five child mortality rate witnessed a major fall
the firm posted 23.35% business growth to 40% from 58% with infant mortality rate falling
as its sales, according to IQVIA, amount- to 34% from 46% six years ago, the MICS 2019
ed to Tk4,715 crore during the period. suggests.

Apart from drug sales on the back of  Pneumonia accounts for 15% of all deaths of children
Covid, a Square Pharmaceutical top of- under 5 years old, killing 808694 children in 2017.
ficial attributed people’s growing pur-
chasing power to surging drug sales. THE PHARMA WORLD 69
According to IQVIA, Healthcare Phar-
maceuticals and Beximco were ahead
of Square in sales during the pandemic.

With Tk. 1,809 crore sales, Health-
care registered the highest 30.37%
sales growth as it succeeded in sales
of hypertension and heartburn drugs
alongside azithromycin. With Tk. 2,467
crore sales, Beximco posted 28.06%
growth to come out second.

Eskayef Pharmaceuticals, which
came out fourth in the IQVIA rank-
ing, logged Tk. 1,169 crore sales during
the pandemic as its sales edged up by
22.02%. Next on the list, Opsonin Phar-
ma registered 18.64% sales growth as its
pandemic sales stood at Tk. 1,454 crore.

Source: The Business Standard



INTERVIEW

We are hopeful that our healthcare
would reach the standard of the
advanced countries very soon

Prof. Dr. A H M Rowshon As an eminent Gastroenterologist pylori related malignant disease is also
Professor of Gastroenterology of the country, would you please found on occasions. Malignant disease
Department of GHPD let us know about the common affecting the small gut are rare, but
BIRDEM General Hospital, Dhaka pancreato-biliary and oncologic adenocarcinoma and lymphoma are
disorders of the gastrointestinal sometimes encountered. Carcinoma of
(GI) tract in our country? colon is another common malignan-
cies of gastrointestinal tract but also
In Bangladesh, like many other of all malignancies. Carcinoma of anal
countries of the world, among the pan- canal are sporadically seen.
creato-biliary diseases, stone diseases
predominate over others in incidence In light of the recent COVID-19
and prevalence. Among them, chole- pandemic, does pre-existing GI
lithiasis or gall bladder stone is found disorders pose a greater risk for
in most of the cases; stones may also COVID-19 complications? What
be found in the common bile (choledo- are the GI symptoms to look
cholithiasis), in the Cystic duct and in out for? What measures do you
the hepatic ducts. Other disease which recommend for its management?
affect the biliary tracts is cholangitis.
Some immunological diseases in the The issue is very relevant for the
form of Primary biliary cholangitis and present time. In general, GI tract is not
primary sclerosing cholangitis are also severely affected by COVID-19 unless
encountered in practice. Cystic diseases the patient is immune compromised
(e.g. Choledochal cyst) are rarely found. or taking drugs which may suppress
Pancreatic diseases are mostly acute the immunological status of the indi-
and chronic pancreatitis. Cystic diseas- vidual. This is common in patients of
es of pancreatic are also not very un- Inflammatory Bowel Disease (IBD) who,
common. Malignant diseases affecting when on immunosuppressant drugs,
Pancreato-biliary tracts are carcinoma steroids or biologics, are immuno-
gall-Bladder, cholangiocarcinoma, peri- suppressed and are more vulnerable
ampullary carcinoma and also solid than their normal counterpart to have
and cystic carcinomas of Pancreas. SARS-CoV-2 infection. These patients
may also develop complications of this
Oncologic disorders, if we start from disease. Another disorder, which may
the upper part of the GI tract, carci- make the patients more vulnerable to
nomas of the esophagus are not very COVID-19, is autoimmune hepatitis as
uncommon in our country. Theses may they are also treated with steroids. Pa-
be in the form of squamous cell carci- tients of any oncological diseases, who
noma or adenocarcinoma depending are on treatment with chemothera-
on whether it is present in the upper peutic agents with or without steroids
or lower part of the oesophagus. Car- are immunosuppressed and are also
cinoma of stomach, is one of the com- similarly prone to have COVID-19 with
mon malignancies not only of gastro- additional complications.
intestinal tract but also of the whole
body. Other cancer which are found in The GI symptoms are anorexia, nau-
stomach are lymphoma and malignant sea and vomiting, but diarrhea may
neuroendocrine cancer. MALT lympho- be the leading complaints of Covid-19
ma, a special variety of Helicobacter patients even in uncomplicated cases.

THE PHARMA WORLD 71

INTERVIEW

Constipation is the complaints in few the IBS symptoms. So, milk and milk for the treatments of Helicobacter Py-
patients. products should be avoided by these lori related PUD, because, all the stud-
group of patients. FODMAP (Ferment- ies done in our country have showed
For prevention we have to maintain able oligosaccharides, monosaccha- that the resistance of Helicobacter Py-
the standard rule. There are interna- rides, disaccharides and polyols) diet lori to clarithromycin is less than 15%.
tional organizations like WHO and should be reduced and Mediterrane-
CDC, who are recommending differ- an diet may also be followed. Being available over-the counter,
ent doses and timing of drugs dur- patients now-a-days are self-
ing the COVID pandemic situation, to Please tell us in brief about prescribing and overusing anti-
minimize these complications. So, we peptic ulcer disease (PUD)? How ulcerant drugs i.e. PPIs. What are the
are following these recommendations common is H. Pylori infection in consequences of such irrational use?
in our practice. But, in general, other our country? How do we treat
than symptomatic treatment, very it and prevent recurrence? It may seem to be irrational, but is
rarely addition of specific treatment logical, because of very high preva-
is required. Peptic ulcer disease is the ulcers lence of PUD all over the world, every
formed in any part of the gastrointes- patient of peptic ulcer disease can not
What are the trigger factors tinal tract, due to the breach of con- consult with the gastroenterologists or
and symptoms for Irritable tinuity of their inner linings (mucosa) physicians. On the other hand, because
Bowel Syndrome (IBS)? Is it by acid-pepsin digestion. Commonly of simple oral route of administration
preventable? What changes in the stomach or the duodenum are the and relatively wide safety profile es-
diet can help the patients? sites of Peptic ulcers disease (PUD). pecially for short term use, PPI’s are
made over-the-counter drugs all over
We know, IBS occurs spontane- Peptic ulcer disease is common all the world, not only in Bangladesh. Ini-
ously, however, there are some factors around the world as in Bangladesh. A tially, parietal cell tumors of stomach
which can stimulate the symptoms to study done in the early eighties found were found in animal studies, but no
develop or to flare. These may be in that around 16% of adult people in our such record was found in human stud-
the form of physical or psychological country suffer from peptic ulcer dis- ies. However, recently, it has been re-
trauma. Mental trauma in any form, ease. With the improvement of socio- ported that, when used for long period
either on personal, social or profes- cultural and economic standard and of time, PPIs may cause recurrent GI in-
sional life, may trigger IBS symptoms change of food processing and tak- fection and diarrhea. Some people are
to develop in all types of IBS. None- ing, the prevalence of PUD is decreas- shown to have developed early osteo-
theless, the diarrheal type IBS is more ing over time. In recent studies these porosis with bone fractures, especially
affected by any form of stress factors. infection have been found prevalent hip bone. Many patients also have re-
Some types of food and GI infections among 5-8% of the populations. Heli- ported to develop pneumonia. Intersti-
can also trigger the symptoms. cobacter Pylori is the leading cause tial nephritis is another complication
of PUD worldwide and also in Bang- of long-term PPI use. Hypomagnesae-
IBS is probably not totally pre- ladesh. In the nineties, a number of mia has recently been recognized as a
ventable. But the symptoms can be studies showed that more than 90% of side effect of PPIs. So, PPIs, apparently
minimized by avoiding the triggering our adult population had been infect- considered safe, should no longer be
factors. If we can maintain the habits ed with H. Pylori and almost all of the considered as safe especially for long
of taking good food, the chance of GI patients of PUD were found H. pylori term indiscriminate use.
infection and inflammation will be positive. Awareness is being devel-
reduced and IBS symptoms are also oped and treatments were given since Please tell us in brief about
expected not to occur or to improve. then. More recent studies have shown Endoscopic Retrograde
Although there is no universal diet that, the prevalence of Helicobacter Cholangiopancreatography
recommended for IBS, but generally, Pylori is around 70-80%. Although the (ERCP). For which conditions
if the patients can identify a particu- prevalence of both H. pylori and PUD can ERCP be used?
lar food that aggravate the symptoms, have reduced, it is still very high, espe-
should better be avoided. By avoiding cially in the elderly population. ERCP is a procedure through which
fatty and fried foods, most of the IBS we can diagnose many pancreato-bil-
patients enjoy better quality of life. Mostly, we treat Helicobacter Pylori iary diseases and also offer treatment
Wheat products may aggravate IBS with combination of antibiotics and for many of the diseases over there.
symptoms in some patients and are an acid suppressing agent, commonly However, nowadays it is almost never
advised to avoid them. Lactose intol- known as triple therapy and quadruple used for diagnostic purpose, as now
erance can be concomitantly present therapy. Clarithromycin is the common a days, we have Magnetic resonance
in IBS patients, and may compound denominator in most of the regimens

72 THE PHARMA WORLD

INTERVIEW

cholangiopancreatography (MRCP) Where does Bangladesh stand es are early diagnosed and appropri-
which is a non-invasive procedure as far as prevention, diagnosis ately treated. Many of them are also
providing almost similar diagnostic and treatment of GI diseases through our national mass vaccina-
results. ERCP is rather used for thera- are concerned, compared to tion program. Our healthcare profes-
peutic purposes in removal of stones the advanced countries? sionals are also maintaining proper
from the biliary tree and the pancre- precautions and anti-septic measures
atic tree, removal of polyp especially Bangladesh is a developing coun- during giving treatment and surgi-
when it is around the ampulla. Worms try, with rapidly developing health- cal procedures. Regarding the non-
from the biliary can also be removed care facilities. With improvement of communicable diseases, awareness
through ERCP. ERCP is used as pal- the economic status, we are improv- is also being built up among our peo-
liation maneuver for biliary and pan- ing our status of hygiene. We are pro- ple. People are better educated about
creatic drainage by placing stents in gressing in prevention and treatment, diabetes, hypertension, liver or kidney
obstructive diseases in conditions like especially of communicable diseases diseases and opting for a healthy life-
cholangiocarcinoma, stricture, steno- by ensuring safe water supply to most style. We are hopeful that our health-
sis, unusually large stones and fibrosis of the people. Proper disposal of hu- care would reach the standard of the
of chronic pancreatitis. man excreta is also almost completely advanced countries very soon.
achieved. Most of the infective diseas-

What’s the difference?

THE PHARMA WORLD 73

GUEST COLUMN

Therapeutic approaches for the Treatment
of Hepatocellular Carcinoma

Introduction Dr Lim Chun Sen and patients simply do not show any
Head of Radiotherapy and Oncology signs of illness such as fever, pain or
Hepatocellular carcinoma (HCC) is one Department, Hospital Sultan Ismail, swelling in the early stages. Very often
of the leading causes of cancer death Malaysia HCC is only detected by chance, when
globally. In Malaysia, HCC is the eighth patients are being treated and/or ex-
most common cause of cancer across pies like radiofrequency ablation (us- amined for something else. These are
both genders. Although it is the fifth ing heat to destroy the cancer), chem- the patients which are referred to me;
most common cause of cancer among otherapy directed into the liver (TACE) the earlier stage patients are usually
males, it is responsible for the sec- or radiation directed into the liver (ra- seen to by the hepatobiliary team.
ond highest number of cancer deaths diation beads released directly into
among men after lung cancer. 1, 2 the liver tumour).3 These therapies The treatment options for late
are used to slow the cancer’s progres- stage patients are basically palliative
Disease staging and treatments sion, stabilise and/ or shrink it. for stage C, with the aim of extending
life as long as possible. For stage D,
Therapeutic approaches for the treat- Chemoembolization achieves > 2.5- treatment is basically symptomatic,
ment of HCC can be classified into year survival rates of up to 75%. For best supportive care (BSC), to try and
three categories: potentially curative, most stage B cancers these therapies make them as comfortable as possi-
palliative, and symptomatic. In my are palliative but occasionally with a ble, with the best possible quality of
hospital we use the Barcelona Clinic stage B cancer presenting just a single life (QoL) we can manage.
Liver Cancer (BCLC) staging system, nodule but with compensated liver
which classifies patients according function, the tumour can be reduced Palliative care
to tumour status, liver function (by to an operable size that makes resec-
Child– Pugh (CP) category), and per- tion viable.4 However, these therapies Since the early 2000s when the
formance status (PS), as either: 0 (very are very expensive and not widely first tyrosine kinase inhibitor (TKI)
early stage), A (early stage), B (inter- available in Malaysia; even in the pri- drug that was effective for HCC called
mediate stage), C (advanced stage), or vate sector. sorafenib was developed, it has been
D (very advanced/end stage). 3 the recommended standard of care
Sadly, almost 85% of all patients for late-stage HCC.2
The early-stages (0 and A) of HCC are already stage C or D by the time
can be treated with potentially cura- the cancer is discovered, and they are TKI drugs have been used to treat
tive therapies such as surgical resec- not suitable for curative surgery or other types of cancer since the 1980s.
tion or local ablation, which offer even loco-regional therapies, as their They are also called molecular-target-
promising 5-year survival rates of up cancer is too far advanced. ed drugs or targeted therapy, as they
to 75%. However, less than 15% of pa- target and inhibit particular pathways
tients are eligible for the potentially HCC is often detected at a late — the proteins or enzymes that pro-
curative treatments1 as the majority of stage as it is largely asymptomatic mote cancer. Unfortunately, for dec-
them present with advanced disease. ades, none had worked for HCC.

If the cancer is detected too late That changed in 2005 when the US
for a curative resection to be feasi- Food and Drug Administration (FDA)
ble, then there are various treatment approved oral sorafenib, a multi-
options to try and control the cancer kinase targeted therapy, which had
and prolong survival. been shown to prolong patients’ sur-
vival in HCC; this meant we finally had
For more advanced stage B, which a palliative treatment to offer late-
are multi-nodular but still localised to stage HCC patients. Although Malaysia
the liver, and preserved liver function, approved the use of the drug within
treatments are basically palliative a couple of years of the FDA, it is not
and revolve around chemoemboliza- covered by government schemes here
tion which is typically performed by a and are only available to patients who
hepatobiliary team and intervention have comprehensive insurance or can
radiologist. afford to cover the cost themselves.

There are now loco-regional thera-

74 THE PHARMA WORLD

GUEST COLUMN

After that first breakthrough with macology has increased the treat- Today we can hope to keep pa-
TKI therapy, there was no second-line ment options for HCC. tients alive with cancer for much
drug to offer patients who failed to longer than was the case 15 years ago,
respond to sorafenib or stopped re- Management of patients but we need the patients to be willing
sponding to it after a few months, un- with advanced HCC and able to cope with the treatments
til the approval of regorafenib in 2017 that are keeping them alive. The best
as the first second-line TKI. Dozens of The Pan-Asian adapted ESMO Clinical way to do that is to give them the best
drugs were developed and evaluated Practice Guidelines for the manage- QoL we can.
by many different companies trying ment of patients with advanced HCC
to find an alternative first-line drug recommend targeted TKI therapies Fortunately, there are some prom-
to sorafenib or a second-line therapy, like sorafenib and cabozantinib as the ising therapeutic developments on
but without success. This forced re- standard of care for late stage HCC.2 the horizon. Ongoing trials combining
searchers to look for alternative ap- However, permission is rarely given targeted TKIs like cabozantinib with
proaches. for their use in government hospitals immunotherapies show promise and
in Malaysia. may soon improve the prognosis and
After a decade or more with no extend the life expectancy of patients
new TKI drugs coming to market, Most of the advanced treatments with HCC, perhaps significantly.
the last three or four years have which are recommended in interna-
produced several new TKI-targeted tional guidelines as the standard of References:
therapies. These include both care for first- and second-line HCC
alternative first-line therapies such treatment are approved for use in 1. Roxburgh P, Evans TR. Systemic ther-
as lenvatinib, and at long last, Malaysia. However, due to cost, none apy of hepatocellular carcinoma:
second-line options. are currently in the Ministry of Health are we making progress? Adv Ther
Formulary, which means patients 2008;25:1089-104. https://pubmed.ncbi.
The latest second-line option to need to make special applications nlm.nih.gov/29963463/
be approved in Malaysia in early 2021, to undergo these treatments, which
is cabozantinib. As each patient and might not be approved. However, if 2. Pan-Asian adapted ESMO Clinical Prac-
cancer is a unique case, not all are patients can afford the treatment, tice Guidelines for the management
suitable for cabozantinib. Cabozan- they can access all the approved of patients with intermediate and ad-
tinib offers significant survival benefit medications available for the treat- vanced/relapsed hepatocellular carci-
for patients who meet the inclusion ment of advanced HCC. Currently, I noma: a TOSeESMO initiative endorsed
criteria for the CELESTIAL trial;5 i.e. am only able to offer older, tradition- by CSCO, ISMPO, JSMO, KSMO, MOS and
they have progressive disease on one al cytotoxic chemotherapies to most SSO https://www.annalsofoncology.
or two systemic therapies, as well as of my public sector patients. org/article/S0923-7534(19)53224-0/full-
well-preserved liver function. text
Whether or not late stage patients
Immunotherapy drugs have access to the latest therapies 3. Richani, M.; Kolly, P.; Knoepfli, M.; Her-
or only cytotoxic chemotherapy; the rmann, E.; Zweifel, M.; von Tengg-
One such alternative that has pro- treatment options are still only palli- Kobligk, H.; Candinas, D.; Dufour, J.-F.
vided a significant advance in recent ative and symptomatic. Symptomatic Treatment allocation in hepatocellular
years has been the development of care refers to therapies intended to carcinoma: Assessment of the BCLC al-
immunotherapy drugs which stimu- ease the symptoms and improve the gorithm. Ann. Hepatol. 2016, 15, 82–90.
late the patient’s immune system to patient’s quality of life (QoL) without http://www.ncbi.nlm.nih.gov/pub-
recognise and attack cancer cells. Im- addressing the basic cause of the dis- med/26626644
munotherapy drugs offer an alterna- ease.
tive therapy for patients who cannot 4. Luciana Kikuchi, Aline Lopes Chagas,
tolerate TKIs or who have progressed The patient’s QoL is an important Regiane S.S.M. Alencar, Claudia Tani,
while on TKIs. consideration as the effects of the Marcio A. Diniz, Luiz A.C. D’Albuquerque,
illness and the side effects of treat- and Flair José Carrilho, Adherence to
The median survival time for ad- ments are often hard to bear. Many BCLC recommendations for the treat-
vanced liver cancer before we had a patients with HCC report suffering ment of hepatocellular carcinoma:
second-line therapy was less than a from pain and fatigue, as well as ex- impact on survival according to stage.
year, and for many Malaysians around periencing side effects from the med- Published online 2017 Aug. doi: 10.6061/
six months. Now, with second-line ication such as diarrhoea, lethargy, clinics/2017(08)01 https://www.ncbi.
therapy options, we can routinely palmar-plantar erythrodysesthesia, nlm.nih.gov/pmc/articles/PMC5577619/
achieve significant improvement on hypertension, nausea, vomiting, etc.,
survival for this group of patients. The making symptomatic care crucial for 5. Ghassan K. Abou-Alfa, Tim Meyer, et al,
addition of cabozantinib to our phar- patients’ QoL. Cabozantinib in Patients with Advanced
and Progressing Hepatocellular Carci-
noma. N Engl J Med, July 2018; 379:54-63
DOI: 10.1056/NEJMoa1717002

https://www.nejm.org/doi/10.1056/NE-
JMoa1717002

THE PHARMA WORLD 75



INTERVIEW

If anyone in this pandemic time experience
new onset of persistent diarrhea,
must be checked for COVID-19

Prof. Dr. Hafeza Aftab Rosy As an eminent Gastroenterologist search on this issue. Key findings are,
Professor & Head of the country, would you please patients with COVID-19 may present
Dept. of Gastroenterology let us know about the common of with only GI symptoms, in addition
Dhaka Medical College & Hospital, pancreatic-biliary, gastrointestinal with COVID-19 symptoms. Similar to
Dhaka & liver diseases of our country? other countries’ outcome in respect
to death, ICU admission, mechanical
Among the common diseases there ventilation, hospital admission are
is Dyspepsia, which is known to all as less in patients with gastrointestinal
‘Gastric”, is the dominant complaint symptoms with COVID-19 infection.
in Gastroenterology followed by IBS
(Irritable Bowel Syndrome), known as If anyone in this pandemic time ex-
Dysentery or Amashoy in local Bengali perience new onset of persistent di-
words. arrhea, must be checked for COVID-19
RT-PCR test. Patients may complaint
Among liver diseases in adult of diarrhea, vomiting, loss of appetite,
population, Hepatitis B virus related following COVID-19 infection. How-
chronic liver disease is very common ever, data is still insufficient whether
in our country. Fatty liver disease is preexisting GI or Liver disorder wors-
also rising. These diseases have huge ens following COVID-19 infection. Con-
socioeconomic impact, as chronic tinuing the treatment even with im-
problems and their unique features munosuppressant’s such as steroid,
regarding management, demand spe- azathioprine for IBD has been prac-
cial attention. ticed without any major complication.

Beside these, IBD (Inflammatory The experience is similar with pre-
Bowel Disease) and Chronic pancrea- existing liver disease patients. COV-
titis, though not more prevalent, are ID-19 may effect liver function with
also contributing to poor quality of raised SGPT in apparently healthy
life with miserable morbidity. adults. Treatment options in such
patients must be individualized with
In my experience, chronic pancrea- great care for COVID-19 symptoms.
titis, obstructive jaundice due to as-
cariasis are more frequent. Carcinoma What are the trigger factors
of esophagus, Gastric cancer, Colon and symptoms for Irritable
cancer, Hepatocellular carcinoma, Bowel Syndrome (IBS)? Is it
GIST are predominant frequency in preventable? What changes in
malignancy list. diet can help the patients?

In light of the recent COVID-19 Exact cause of IBS is not known.
pandemic, does pre-existing GI Sometimes it starts after severe infec-
disorders pose a greater risk for tion, diarrhea or stressful situation.
COVID-19 complications? What Gut bacteria, micro biota, genetics,
are the GI symptoms to look mental health (anxiety or stress), hor-
out for? What measures do you mone, diets also affect IBS.
recommend for its management?
It is not preventable, but you can
More than1- ½ years have passed control it with diet regulations, relax-
with COVID-19 and now the worldwide ation therapy etc. Diet has great role
data are coming up. We are doing re-

THE PHARMA WORLD 77

INTERVIEW

for IBS patients. It is more individu- prescribed. Prevention of recurrence How common is GERD in our country?
alized; in general, we recommend can be reduced by maintenance ther- Can it lead to malignancy? How can
to avoid dairy products, high sugar, apy, eliminating the cause of ulcers we prevent such complications?
fat, carbohydrate containing diet, such as NSAID, Helicobacter pylori and
spicy foods, gluten containing foods, quit smoking habit. GERD is not much common in our
fried foods, pulses, artificial sweet- country (<10%) compared to the west-
eners etc. e.g. milk, cheese, cauli- Being available over-the counter, ern countries. Increasing in recent
flower, broccoli, cabbage, beans, al- patients now-a-days are self- years following change of food hab-
cohol caffeine, soda, chewing gum, prescribing and overusing anti- its, life style in urban population. May
nuts etc. ulcerant drugs i.e. PPIs. What lead to cancer in course of time fol-
are the consequences of such lowing development of Barrett’s Es-
Please tell us in brief about peptic irrational use in long term? ophagus.
ulcer disease (PUD)? How do we
treat and prevent recurrence of PUD? After introduction of PPI in the Where does Bangladesh stand
eighties, it is top list OTC drug as far as prevention, diagnosis
PUD treatment is very promising. throughout the whole world. Re- and treatment of GI diseases
Now a days there are number of acid search is going on, some published are concerned, compared to
secretory inhibitors, acid neutralizing data from observational studies have the advanced countries?
drugs, mucosa protecting agents and reported bone loss, renal impairment,
antibiotics. It is necessary to find out dementia, and diarrhea from oppor- Compared to the advanced coun-
the cause behind the ulcer, e.g if the tunistic infection. tries, Bangladesh is moving forward
patient is taking painkiller. If it is due in this field. We need more logistic
to Helicobacter pylori a standard re- Besides health related side effects, supports, research, practice of ethical
gime of eradication therapy may be it is also costing the patients econom- & judicial use of endoscopic proce-
ically. dures.

78 THE PHARMA WORLD

CORONA UPDATE

IL-6 and corticosteroid use reduces demonstrated the highest potential to be used as oral COVID-19
28-day mortality In COVID-19 patients therapies, based on factors such as potency, likely mechanism
of action and safety, the researchers said. Four of the 13 drugs
A meta-analysis of 27 randomized trials investigating the – halofantrine, nelfinavir, simeprevir and manidipine – are
effect of IL-6 antagonists on 28-day mortality among hospital- already FDA-approved and the nine others are in various stages
ized COVID-19 patients found that patients who received IL-6 of development, according to the study. Two additional drugs
antagonists had a lower mortality rate than those receiving heightened remdesivir’s ability to suppress the virus, the study
either usual care or placebo (22% vs. 25%). Additionally, ab- found: These two drugs were riboprine, a compound that’s
solute 28-day mortality risk fell to 21% with corticosteroid use been tested as a preventative for nausea and surgical infection,
compared to 25% for those receiving usual care or placebo. and 10-deazaaminopterin, a derivative of the vitamin folic acid.

Many existing drugs could CPAP may reduce need for invasive
be potent COVID fighters mechanical ventilation

It has been an elusive goal so far – finding a potent treatment Continuous positive airway pressure (CPAP) reduced the need for
that can beat back the new coronavirus before it grabs a hold invasive mechanical ventilation in adults admitted to hospital
of a patients immune system and sends it into overdrive. Inves- with acute respiratory failure due to covid-19, a trial has found.
tigators tested more than 12,000 drugs in two different types of The trial compared CPAP, high flow nasal oxygenation (HFNO),
human cells infected with SARS-CoV-2. From those thousands and conventional oxygen therapy among inpatients with
of drugs, the researchers identified 90 that prevented SARS- covid-19 who required oxygen therapy, looking at the rates of tra-
CoV-2 from replicating in at least one of the human cell lines. Of cheal intubation or mortality within 30 days with each treatment.
those drugs, 19 were found to work in concert with or boost the Looking at a composite outcome of intubation or death within
activity of remdesivir, an antiviral therapy already approved for 30 days of randomisation, the study reported that the need for
treatment of COVID-19. Of the 19 drugs that showed promise, 13 tracheal intubation or mortality was lower in the CPAP group
(36.3%) than in the conventional oxygen therapy group (44.4%).

C.1.2 Covid variant may be more infectious, evade vaccines

Anew variant of SARS-CoV-2, the virus which rate of about 41.8 mutations per year, which is about
cause COVID-19, has been detected in South twice as fast as the current global mutation rate of
Africa and many other countries globally which the other variants. Over half of the C.1.2 sequences
could be more transmissible and evade protection have 14 mutations, but additional variations have
provided by vaccines, according to study. been noticed in some of the sequences.

Scientists from National Institute for Communica- “Though these mutations occur in the majority of
ble Diseases (NICD) and the KwaZulu-Natal Research C.1.2 viruses, there is additional variation within the
Innovation and Sequencing Platform (KRISP) in South spike region of this lineage, suggesting ongoing intra-
Africa said the potential variant of interest, C.1.2, was lineage evolution,” the authors of the study noted.
first detected in the country in May this year.
About 52% of the mutations in the spike region
C.1.2 has since been found in China, the Demo- of the C.1.2 sequences have previously been seen in
cratic Republic of the Congo, Mauritius, England, New other VOCs and VOIs. The spike protein is used by
Zealand, Portugal and Switzerland. the SARS-CoV-2 virus to infect and enter human cells,
and most vaccines target this region. The mutations
According to the yet-to-be peer-reviewed study N440K and Y449H, which have been associated with
posted on the preprint repository MedRxiv on August immune escape from certain antibodies, have also
24, C.1.2 has mutated substantially compared to C.1, been noticed in C.1.2 sequences.
one of the lineages which dominated the SARS-CoV-2
infections in the first wave in South Africa. These mutations together with changes in other
parts of the virus likely help the virus evade antibod-
The new variant has more mutations than other ies, and immune response, including in patients who
variants of concern (VOCs) or variants of interest have already developed antibodies for the Alpha or
(VOIs) detected worldwide so far, the researchers said. Beta variants.

According to the study, C.1.2 lineage has a mutation

THE PHARMA WORLD 79



INTERVIEW

To ensure optimum hepatic function,
active lifestyle and balanced diet
are of prime importance

Dr. Faroque Ahmed As an eminent Hepatologist of diaseae (NAFLD)? How often can
Associate Professor & Head the country, would you please let NAFLD progress to Nonalcoholic
Department of Hepatology us know about the prevalence of steatohepatitis (NASH)? What
Dhaka Medical College & Hospital liver diseases in our country? can be done to prevent it?

Prevalence of various Liver dis- Obesity, dyslipidemia, sedentary
eases varies in different parts of the lifestyle and underlying diseases like
world. In Bangladesh prevalence of diabetes mellitus, hypothyroidism
the common liver diseases are non- etc. can be considered as risk factor
alcohol liver diseases 33% (approx.) for NAFLD.
chronic Hepatitis B 5.7%, Chronic Hep-
atitis C 1% (approx.), according to sev- Liver biopsy can confirm the sub-
eral population based studies. About sets of NAFLD patients who have
20,000 people die each year due to necro-inflammation and fibrosis
chronic liver disease and its various (NASH). In various studies, it have
complications been estimated that about 20% of
NAFLD patients have NASH; this ratio
In light of the recent COVID-19 may reach 27% by the year 2030.
pandemic, does pre-existing
liver disease (chronic liver To prevent this, lifestyle modifica-
disease, cirrhosis, or related tion, weight reduction, treatment of
complications) pose a greater underlying disease and some rec-
risk for COVID-19 complications? ommended medications may help to
What measures do you recommend combat NAFLD.
for its management?
What are the risk factors for
Yes, pre-existing liver disease, es- developing liver cirrhosis? How
pecially decompensated cirrhosis of can we prevent it? What are
liver, fatty liver diseases and other your suggestions to ensure
forms of chronic liver diseases carry optimum hepatic function?
greater risk of COVID-19 complica-
tions. Liver cirrhosis refers to a shrunken
scarred and hardened liver with de-
So, besides continuing ongoing terioration of liver function and show
managements of liver diseases, those histological evidence of fibrosis and
who are infected with COVID-19 infec- nodule formation.
tion, active management for COVID-19
infection and its complications like Risk factors from liver cirrhosis:
thrombo-embolic manifestations chronic Hepatitis B, chronic Hepatitis
should be managed accordingly. C, fatty liver disease, chronic exces-
Close monitoring and hospital admis- sive alcohol intake, autoimmune liver
sion is crucial part in management of disease, Wilson disease, Hemochro-
COVID-19 in patients with pre-existing matosis etc.
liver diseases patients.
Prevention:
What are the risk factors of Preventive measures for Hepatitis
developing Non-alcoholic fatty liver for Hepatitis B & C infection includ-
ing vaccine for Hepatitis B. If infected,
treatment of Hepatitis B, C.

THE PHARMA WORLD 81



INTERVIEW

1. Balanced diet tion, Trans Arterial Chemoemboliza-
2. Maintainence of Healthy tion (TACE) and drugs.

weight Please tell us, in brief, about the
3. Regular exercise or physical prevalence of Viral Hepatitis
in Bangladesh? What are
work your suggestions to create
4. Avoidance of Alcohol awareness among the common
5. Treatment of underlying liver people about viral Hepatitis?

disease under guidance of In Bangladesh, various popula-
specialist physician to present tion based study showed that prev-
chronic liver disease. alence of Hepatitis B is 5.7% and
Hepatitis C is 1% (approx.). Though
To ensure optimum hepatic func- recent studies, revealed further de-
tion following measures can be tak- cline in prevalence.
en:
Hepatitis B & C viral infection can
l Active lifestyle and regular ex- cause chronic liver disease, cirrho-
ercise Balaced diet containing sis and its complications like liver
more fibres and less carbohy- cancer. Those who are infected,
drates rates and fatty foods. must consult with specialist physi-
cian for appropriate treatment and
l Maintaining ideal body weight regular monitoring.
l Vaccination against Hepatitis A,
As we know, prevention is far bet-
B. ter than treatment, following meas-
l Caution to take herbal, indig- ures can be disseminated to com-
mon people through print, electronic
enous and traditional medi- media, seminars, conferences and
cines. other direct audio visual contacts.
l Treatment of Hepatitis B, C
or other liver diseases under All children and also adults
specialized physicians super- should take vaccine for hepatitis B,
vision. especially health care workers and
l Management of underlying family members of Hepatitis B, C
diseases like diabetes melli- infected patients must also be vac-
tus, hyperlipidemia, hyperten- cinated.
sion, hypothyroidism.
l Avoidance of alcohol is of l Avoid sharing personal items
prime importance. used as tooth brush, razors
etc.
Please tell us in brief about
Hepatocellular carcinoma l Avoid sharing needle used in
and its treatment? drug abuse

Hepatocellular carcinoma or l Tattooing, body piercing
primary liver cancer arise usually l Practice safe sex
in the context of cirrhosis, second l Ensure screening of donated
most lethal cancer worldwide.
Management depends on stages, blood before transfusion of
size of the tumor, involvement of blood or blood products
different lobes of livers, distant
metastases and patients general Proper treatment of Hepatitis
conditions. B, C infected patients can prevent
liver cirrhosis and liver cancer. So,
Available treatment modalities we must convince our surrounding
are hepatic resection, transplanta- people to disseminate this informa-
tion (not-available in Bangladesh), tion to help eliminate hepatitis by
microwave or radio frequency ab- 2030.
lation, percutaneous alcohol injec-

THE PHARMA WORLD 83

RESEARCH UPDATE

Incomplete Polyp Removal 23% in colon segments where polyps nesses such as heart disease and help
Can Bring Cancer Danger had been completely removed, the the environment. Now, new research
findings showed. And the prevalence suggests they may provide another
Colonoscopy screening can help of advanced polyps — ones with a health benefit: lowering COVID-19 se-
prevent colon cancer by allowing doc- greater cancer potential — was six verity. A plant-based diet was associ-
tors to find and remove potentially times higher in colon segments where ated with 73% lower odds of moderate
pre-cancerous growths called polyps. there’d been an incomplete removal: to severe COVID-19 infection in the
But if they fail to get the whole growth, 18% versus 3%. Experts said the study. Plant-based diets were de-
the odds of a recurrence are high, a findings point to the importance of scribed as high in vegetables, legumes
new study shows. The likelihood that doctors’ technical skills, not only in and nuts and low in poultry and red
it will occur within the next few years finding polyps, but in removing them. and processed meats. The researchers
more than doubled. Repeat exams Past studies have also estimated that noted that plant-based diets are rich
found a new growth in the same colon incomplete polyp removal contributes in nutrients, especially phytochemicals
segment 52% of the time compared to to anywhere from 10% to 30% of colon (polyphenols, carotenoids), vitamins
cancers that develop after colonos- and minerals, which are important
copy screening. for a healthy immune system. Fish is
an important source of vitamin D and
Could a Meat-Free Diet Help omega-3 fatty acids, both of which
Ward Off Severe COVID? have anti-inflammatory properties. A
pescatarian diet, which includes fish
Advocates of plant-based diets suggest but limits or eliminates meat, was
they can reduce the risk of chronic ill- associated with 59% lower odds. Com-
pared to those who ate a plant-based
diet, those with a low-carb, high-
protein diet had nearly four times the
odds of moderate to severe COVID-19
infection, according to the study.

Heart Failure Patients May Statin Users May Have Added
Be at Higher Cancer Risk Protection against Severe COVID-19

Living with heart failure is hard enough, but a new study suggests that Could cholesterol-lowering statins help
these patients may also face a higher risk of cancer. Researchers looked at lower your risk of dying from COVID-19?
more than 100,000 heart failure patients and the same number of people For patients with a history of high blood
without heart failure. Their average age was just over 72 and none had pressure or heart disease, the answer
cancer at the start of the study. Over 10 years of follow-up, cancer rates appears to be yes. At least that’s the
were 25.7% among heart failure patients and 16.2% among those without
heart failure. By gender, rates were 28.6% in women with heart failure,
18.8% in women without heart failure, 23.2% in men with heart failure and
13.8% in men without heart failure. The findings suggest that heart failure
patients may benefit from cancer prevention measures.

84 THE PHARMA WORLD

RESEARCH UPDATE

conclusion of a new study that enlisted Immune-Based Therapy May Help Some
roughly 10,500 patients for about a year. Battling Advanced Colon Cancers
All had been admitted with a serious
bout of COVID-19. Prior to hospitaliza- Immunotherapy helped extend the lives of some patients with the most
tion, 42% had been taking statins to common type of advanced colon cancer, researchers report. The new find-
rein in high cholesterol, with 7% taking ings are important, they noted, because immunotherapy doesn’t typically
statins alone and 35% taking both work against microsatellite stable (MSS) colon cancer. This study included
statins and blood pressure medications. patients with MSS colon cancer that had become resistant to chemo
In the end, about a fifth of the patients and had spread. They were treated with an immune checkpoint inhibi-
either succumbed to COVID-19 or were tor PD-1/PD-L1 targeted therapy. The median time of disease progression
discharged to a hospice setting. After for patients whose cancer had not spread to the liver was four months,
analyzing data, the team also concluded compared to one and a half months for those whose cancer had spread
that statin use was similarly linked to a to the liver, the study found. When stratified the patients by the presence
25% lower risk for developing a “severe or absence of liver metastases, 20% of patients without liver metastases
outcome” as a result of COVID-19 infec- had a major response to anti-PD-1 or anti-PD-L1 therapy, the researchers
tion. Researchers noted that statins noted. None of the patients whose cancer had spread to the liver had a
pack a potentially helpful anti-inflam- positive response.
matory punch, stabilizing the underly-
ing heart conditions for which they are
prescribed, making patients more likely
to recover from COVID-19. The team
found that statins drove death risk
down by 16% among patients with no
prior history of heart disease.

Could Too Many Antibiotics Raise
Your Odds for Colon Cancer?

Antibiotics may increase the risk treat a wide range of infections -- ZED1227, inhibits the activity of an
of colon cancer, especially in younger were associated with these cancers. enzyme called transglutaminase 2
people, researchers report. The Researchers said their findings add (TG2) in the intestines. TG2 plays a
researchers’ comparison of data from to concerns about the effects of an key role in the autoimmune response
nearly 8,000 people with colon and estimated 65% increase in worldwide that marks celiac. The researchers
rectal cancer to folks without the antibiotic use between 2000 and 2015. randomly assigned the patients to
disease found an association between one of four groups: three were given
antibiotic use and an increased risk New Drug Shows Real Promise various doses of ZED1227 to take every
of colon cancer at all ages. The study Against Celiac Disease morning for six weeks; the fourth took
found significant age-related differ- placebo pills. Thirty minutes after
ences, however. Antibiotic use was An experimental drug can prevent each morning dose, the study patients
linked with a nearly 50% higher risk intestinal damage caused by ce- ate a biscuit containing a moderate
of colon cancer in folks under age 50, liac disease— raising hopes that it amount of gluten, as a way to test the
and a 9% higher risk in older people. could become the first medication drug’s ability to block gluten-induced
In younger people, antibiotic use was for the serious digestive disorder. inflammation. After six weeks, the trial
linked to cancers in the colon’s right The new study looked at whether an found, patients on any dose of the
side. Quinolones and sulfonamides/ experimental drug can prevent that drug showed fewer signs of intestinal
trimethoprim -- antibiotics used to intestinal damage. The drug, dubbed damage, versus the placebo group.

THE PHARMA WORLD 85



WHATS NEW

India designs molecular sensor tract, researchers invented a nasal
to identify cancer drugs spray influenza vaccine that is more
effective than an injection.

Since breathing and eating inevi-
tably introduces foreign antigens into
the body, the mucous membranes in
the respiratory and oral-fecal tract
have a mucosal tolerance to patho-
gens, making it difficult for vaccines
to elicit mucosal immunity. This is
what makes developing a mucosal
vaccine more challenging than devel-
oping an injection.

Researchers from InStem India, in collaboration with Curie institute, Hong Kong links
Orsay, France, funded by Indo-French Centre for the Promotion of Ad- hyocholic acids with
vanced Research (IFCPAR/CEFIPRA), a bilateral organization supported diabetes treatment
by Department of Science of Technology (DST), government of India
and government of France, have recently developed a molecular sen- A series of studies have revealed that
sor, which can identify cancer drugs by detecting how much chemicals hyocholic acid and its derivatives
modify microtubules inside living cells. (collectively known as HCAs), a com-
ponent of bile acids that facilitate fat
The researchers have devised a method to design synthetic proteins, digestion, are a promising risk indi-
known as nanobodies which can bind specifically to modified microtu- cator of type 2 diabetes. The strong
bules. These nanobodies are similar to antibodies made in our body as efficacy of HCAs in regulating blood
a defense mechanism against pathogens. However, unlike antibodies, glucose levels and protecting against
the nanobodies are smaller in size and easily amenable for protein engi- diabetes has also been uncovered.
neering. The nanobody was then coupled with a fluorescent molecule to The findings open a window for the
serve as a detection tool, called sensor. They developed and validated a development of HCA-based predic-
live cell sensor against a unique microtubule modification called tyrosi- tive drugs.
nated form of microtubules that is already known to be important for
cell division and intracellular organization. The tyrosination sensor can The study indicates the potential
facilitate studying microtubule functions for many researchers and will role of HCAs in the maintenance of
aid identifying new drugs of therapeutic value. stable glucose levels. It was discov-
ered that the levels of serum HCAs
Taiwan develops which vaccines to prepare for the next were significantly lower in the healthy
vaccine against all influenza season is challenging, and a obese and obese with type 2 diabetes
influenza strains wrong guess can lead to a low vaccine groups. Those who had become met-
efficacy. abolically unhealthy, had significantly
A research team at the National Tsing lower baseline levels of serum HCAs,
Hua University (NTHU) in Taiwan has According to the researchers, this illustrating that levels of HCAs are a
developed a vaccine providing pro- is mainly because the hemagglutinin strong predictor of metabolic syn-
tection against all strains of influenza. of the influenza virus is constantly dromes such as diabetes. The study
The vaccination can be administered changing, making it difficult for our also revealed that HCAs are the most
in the form of a nasal spray instead immune cells to recognize it. The effective at stimulating secretion of
of by injection. Since the prevalence team has deglycated the stem region glucose-dependent insulin tropic
of influenza and the strains involved of the hemagglutinin antigen, which peptide (GLP-1) when compared with
differs from year to year, deciding on makes it easier for immune cells to other types of bile acids. The findings
recognize and eliminate the virus. disclosed that HCAs regulate blood
Since influenza viruses are mainly glucose levels by stimulating the se-
transmitted through the respiratory cretion of GLP-1 and thus insulin pro-
duction.

Source: BioSpectrum

THE PHARMA WORLD 87

TECHNOLOGY

Optical Fiber Imaging for Next- Tiny Robots Walk Through Colon
Generation Endoscopes to Deliver Drugs, Sample Tissue

Researchers have developed a technique to image Engineers at Purdue University have come up with
tissues through an ultrathin optical fiber, poten- cheap, non-toxic and biocompatible tiny robots,
tially allowing for high-resolution imaging of single controlled by an external magnetic field, that can
cells within the body. The optical fibers are as thin tumble through the colon to deliver drugs precisely
as a human hair, and could lead to tiny endoscopes where needed. They may even serve as a minimally
that can be inserted into human tissues to image invasive and more comfortable way to take biopsies
individual cells. If developed further, the technique within the colon. A rotating magnetic field provides
could help clinicians identify diseased cells within the energy for them to move and is also used to
the body, and help with the accurate placement of direct their travel. Because they tumble, these de-
needles to obtain biopsy samples. Conventional en- vices can pass over relatively large objects, such as
doscopes are limited to inspecting tissues at a gross those found on the irregular surface of the colon’s
level, and individual cells remain a mystery unless interior. The researchers loaded their robots with
removed from the body and analyzed using bench- microscopic drug vials that were filled a fluorescent
top microscopes. Single-cell imaging  in vivo  re- liquid. The robots were able to deliver their vials to
mains out of reach for conventional endoscopy, but the intended destinations and remained there to let
this latest technology may be about to change that. the vials slowly release the fluorescent substance,
which was easily detected using a light source.

Intestinal Organoids Mimic Human Gut medicine, drug screening, and even paving the way for
researchers to grow new tissues and organs in the lab
Researchers in Switzerland have developed a mini in- for use in regenerative medicine. The Swiss research-
testine on a chip that closely mimics the morphology ers have used a gut shaped template, laser-sculpted
and cellular composition of the small intestine. The within a hydrogel in a microfluidic channel, to guide
device could be useful for advancing personalized stem cells into the correct tissue arrangement that
mimics the small intestine. The microfluidic system
allowed a long-lived homeostatic organoid system in
which cell birth and death are balanced. “Our work
shows that tissue engineering can be used to control
organoid development and build next-gen organoids
with high physiological relevance, opening up exciting
perspectives for disease modelling, drug discovery,
diagnostics and regenerative medicine,” the research-
ers explained.

88 THE PHARMA WORLD

TECHNOLOGY

Electronic Pill Popping to Detect GI Bleeds

EnteraSense, an early-stage startup based in Gal-
way, Ireland, has developed a device that uti-
lizes the “Pill Cam” form factor to detect
upper GI bleeds. The swallow-able
capsule endoscopy devices are
able to withstand the harsh,
acidic environment of
the gut, and can provide
high-resolution images,
as well as temperature,
pH, and pressure data.

Bacterial Hydrogel Adheres to Gut to 3D Printed Shields
Treat Inflammatory Bowel Disease Protect Guts During
Radiotherapy
Scientists have developed a living bacterial hydrogel that can adhere
to lesions in the gut wall to encourage healing and reduce inflam- Researchers in Massachusetts
mation. “The ‘Probiotic Associated Therapeutic Curli Hybrids’ (PATCH) have developed 3D printed
approach, as we named it, creates a biocompatible, mucoadhesive shields to protect the GI tract from
coating that functions as a stable, self-regenerating BAND-AID® and the side effects of radiotherapy
provides biological cues for mucosal healing,”said a researcher in- like esophagitis and proctitis to
volved in the study. The bacterial hydrogels can be ingested orally, mucositis. Using CT scans, the
and will travel through the gut before adhering to a lesion. The bac- devices can be custom printed to
teria secrete a modified protein that binds to mucus and forms na- suit each patient’s anatomy. The
nofibers on the bacterial cell surface. So far, the researchers have materials they’re made of contain
tested the gels in a mouse model of inflammatory bowel disease, high atomic number elements
with promising results. that help to shield tissues from
gamma and X-rays. The research-
ers have simulated how the de- Source: Medgadget
vices would work in humans and
have estimated that they would
reduce radiation exposure in the
mouth by up to 30% in head and
neck cancer patients, and by up to
15% in the gastrointestinal tract in
prostate cancer patients.

THE PHARMA WORLD 89



GLOBAL MARKET SURVEY

prevalence of peptic ulcers a major factor
boosting growth to Drugs Market

Overview iron. Due to a reduction of normal in- ket’s proton pump inhibitors segment
testinal flora, there is a chance of op- was worth US$ 24,799.4 million in 2018,
By the end of 2027, the worldwide pep- portunistic infections with S. pneumo- which is projected to grow at a CAGR
tic ulcer drugs market is expected to nia and C. defficile. The global peptic of 2.8 percent to US$ 31,895.7 million
be worth US$ 45,951.2 million. ulcer drugs market is estimated to be by 2027.
hampered as a result of this situation.
On the other hand, according to Regulations
360researchreports, the global anti- Opportunities
peptic ulcer drugs market size is pro- The US FDA is currently reviewing the
jected to reach USD 16340 million by To increase their market share, major risk of Clostridium difficile–associated
2026, from USD 7691.6 million in 2020, competitors should concentrate on diarrhea (CDAD) in users of histamine
at a CAGR of 13.4% during 2021-2026. customized care and management of H2 receptor blockers. H2 receptor
PUD patients. Researchers from the blockers are used for the treatment
Drivers Institute of Medical Microbiology in of gastro esophageal reflux disease
Switzerland hypothesized in a report (GERD), stomach and small intestine
The high demand for Anti-Peptic Ulcer published in the Journal of Clinical ulcers, and heartburn.
Drugs which is used in various appli- Medicine in 2019 that next-generation
cations such as Gastritis, Gastric Ul- sequencing technologies could help Key Developments
cers, Duodenal Ulcers, Gastroesopha- with rapid monitoring of virulence
geal Reflux Disease (GERD) will drive determinants in H. pylori, which could To broaden their product range, key
the Anti-Peptic Ulcer Drugs market. help with targeted care and control of market players are focusing on prod-
patients with PUD. uct acceptance and launch. Talicia, a
The rising prevalence of peptic ul- treatment for Helicobacter pylori (H.
cers is expected to propel growth of High doses of NSAIDs (non-steroidal pylori) infection in adults, regardless
the global peptic ulcer drugs market anti-inflammatory drugs) have also of ulcer status, was approved by the
during the forecast period. As per the been linked to an increased risk of US FDA in November 2019.
report, ‘A36 The Global Prevalence of chronic PUD. Thus, market players may
Peptic Ulcer Disease and Its Compli- concentrate their research and devel- In October 2019, Novitium Pharma
cations at the Turn of the Twenty-First opment efforts on H. pylori eradica- LLC made a recall of ranitidine hydro-
Century: A Systematic Review,’ Spain tion therapy, which has the potential chloride capsules in the U.S. due to
had the largest annual incidence of all to reduce the risk of persistent PUD in elevated levels of NDMA (N-Nitros-
PUD of 141.8 cases per 100,000 people. NSAID users. odimethylamine), a suspected human
carcinogen, above the FDA’s limits.
Furthermore, changes in lifestyle, The global peptic ulcer drugs mar-
such as stress, diet, and a high preva- Source: Coherent Market Insights,
lence of smoking, are projected to 360researchreports
drive growth of the global peptic ulcer
drugs market over the forecast peri-
od. According to the World Health Or-
ganization, 1.337 billion people glob-
ally smoked cigarettes in 2018.

In terms of value, North America
dominated the global peptic ulcer
drugs market in 2018, contributing
about 41.4 percent of the overall mar-
ket share, led by Europe.

Restraints

Extended use of peptic ulcer medica-
tions including proton pump inhibi-
tors and antibiotics will increase the
risk of hip bone fracturing by reduc-
ing the capacity to digest calcium and

THE PHARMA WORLD 91



API MARKET

The global API market is expected to reach
approximately $300 billion by 2030

The global active pharmaceutical ingredient market stood at around
$190 billion in 2020, and it is expected to reach approximately
$300 billion by 2030. This can be attributed to the widening of the
application area of drugs, expiration of patented biologics, increase
in the incidence of chronic and lifestyle-associated diseases, such
as cancer, diabetes, and cardiovascular diseases, rise in the geriatric
population, government initiatives to promote generic drugs,
investments in biosimilars, increasing healthcare expenditure, and
surging awareness about diseases.

n TPW desk peutic application. This would be ment for COVID-19. Additionally, in
driven by the high prevalence of can- April 2020,  Boehringer Ingelheim  In-
Due to the  COVID-19  pandemic, cer and increasing demand for highly ternational GmbH. acquired Northern
lockdowns were imposed by the potent APIs (HPAPIs) for its treatment. Biologics, which focuses on thera-
government in several countries peutic antibodies targeting the tumor
across the world, which disrupted the Asia-Pacific (APAC) to experience microenvironment, to combat cancer
supply chain and economic activity highest CAGR in forecast period and other serious diseases. This ac-
during the first half of 2020. However, due to large patient pool quisition broadened Boehringer In-
established pharmaceutical and bio- gelheim’s oncology product portfolio.
tech companies, as well as research APAC is expected to witness the fast-
institutes, stepped forward to devel- est growth during the forecast period Rising geriatric population to play
op a treatment against the coronavi- (2021–2030). This will be due to the large major role in market growth
rus, which had a positive impact on patient pool, surge in the healthcare ex-
the API market. penditure, and the existence of a large The increasing life expectancy is a
With Rising Drug Discovery Activi- number of companies manufacturing major contributor to the growth in the
ties, Innovative APIs Category Domi- generic drugs in the region. Additional- geriatric population. As per the Unit-
nated Market. The innovative APIs ly, an increasing number of people are ed Nations Department of Economic
category held the larger share in the becoming aware about lifestyle-associ- and Social Affairs (UNDESA) report
market for active pharmaceutical in- ated diseases, which is further driving World Population Ageing 2019, the
gredient during the historical period, the industry progress in the region. population of people aged 65 years
based on type, and it is expected to re- or above is projected to double to 1.5
tain its position in the upcoming years. Mergers, acquisitions, and billion by 2050. Globally, the share of
The increasing drug research and de- partnerships are key trends this population increased from 6%
velopment (R&D) initiatives by innova- in 1990 to 9% in 2019, and it is pro-
tor API companies, favorable govern- Over the past decade, the API mar- jected to rise further to 16% in 2050.
ment regulations, and launch of novel ket has witnessed a large number of The elderly require extensive care as
and more-effective medicines are the mergers, acquisitions, and partner- they need a longer recovery time and
key factors contributing to the growth ships globally. For instance, in August are more prone to illnesses owing to
of the innovative APIs category. 2020,  Pfizer  Inc. announced a multi- their low immunity level. Therefore,
The oncology category is expected year agreement with Gilead Sciences to cater to the increasing demand for
to register the highest CAGR during Inc. to manufacture and supply the drugs to treat different diseases and
the forecast period, based on thera- latter’s investigational antiviral rem- disorders in the elderly, the consump-
desivir, in an effort to scale up the tion of APIs is surging.
supply of the investigational treat-

THE PHARMA WORLD 93

FAQ

Can you live with Crohn’s Can you ever stop biologics?
without medication?
It’s usually best not to stop taking a biologic, since most
The condition usually doesn’t get better on its own or go of these medications don’t work as well when restarted.
into remission without treatment. In fact, it will probably Reasons you might stop taking a biologic include failure
get worse and lead to serious complications.  to respond well to the medication, serious side effects,
pregnancy, elective surgery, and necessary vaccinations.
What is the best medicine for IBD?
Do Biologics lower your immune system?
Anti-inflammatory drugs are often the first step in the
treatment of inflammatory bowel disease. Anti-inflam- All biologics suppress the immune system and increase
matories include corticosteroids and aminosalicylates, the risk of infections such as upper respiratory infections,
such as mesalamine, balsalazide and olsalazine . pneumonia, urinary tract infections, and skin infections.

When do you use biologics in IBD? Do biologics affect T cells?

Biologic medicines are treatments for people with mod- Anti-TNF can regulate the T-cell responses in many ways.
erate to severe Crohn’s Disease or Ulcerative Colitis. They By inducing iTregs through TNF-RII and restoring T-cell
may be an option when other drugs such as immunosup- function, these biologics contribute to reducing the au-
pressants (azathioprine, mercaptopurine, methotrexate) toimmune process.
or steroids haven’t been effective, or side effects have
been hard to manage. What is the difference between
gastritis and gastroenteritis?
How do biologics work in IBD?
Gastroenteritis is characterised by irritation and inflam-
Biologics work by targeting and suppressing the inflam- mation of the stomach, and also the intestines. This con-
mation response that can trigger Crohn’s flares. dition is typically caused by a viral or bacterial infection.
Parasites, food allergens (allergies), or adverse reactions
What is the safest biologic to types of medications or antibiotics are also known
for ulcerative colitis?  causes. Symptoms associated with gastroenteritis include
watery diarrhoea, vomiting and nausea, cramping, fever
A 2020 review found that Vedolizumab was the safest bio- and headaches. Gastritis, however, only involves the in-
logic for treating ulcerative colitis. It was linked to the low- flammation, irritation, or erosion of the protective lining
est number of infections. The authors ranked Ustekinum- of the stomach. Treatment for gastroenteritis is generally
ab as the next safest biologic for treating ulcerative colitis. the same as for gastritis, along with anti-microbial medi-
cations where more severe cases are diagnosed.
How long can you use biologics for?
How long does gastritis last?
Long-term studies have so far found that anti-TNF agents
are acceptably safe. People with moderate-to-severe ul- A bout of gastritis can range from as little as a few hours
cerative colitis may need to use biologics on an ongoing to several weeks, depending on the cause and severity
basis to keep the condition in remission. Stopping treat- of damage to the stomach lining. Usually, if the source of
ment with biologics may cause a relapse, during which the problem is food or beverages, cutting out these irri-
symptoms return. tants from your diet can alleviate symptoms within a few
hours. If caused by a bacterial infection, the severity of
Do biologics cause weight gain? the inflammation can take up to a few weeks to clear up
with adequate treatment, as recommended by a medical
One  small study  followed 269 people with IBD, includ- professional.
ing 106 people with ulcerative colitis. The researchers
linked treatment with anti-TNF agents, Vedolizumab, and Why is upper endoscopy done?
Ustekinumab to slight weight gain. People who started
treatment with biologics gained an average of 1.33 kil- Upper endoscopy helps your doctor evaluate symptoms
ograms (kg) to 2.31 kg after 54 weeks. Weight gain was of persistent upper abdominal pain, nausea, vomiting,
higher in people with Crohn’s disease than those with difficulty swallowing or the cause of bleeding from the
ulcerative colitis. upper gastrointestinal tract.

94 THE PHARMA WORLD

RED ALERT

Clonidine Hydroxyethyl Starch Products

The Therapeutic Goods Administration (TGA) has The U.S. Food and Drug Administration (FDA) is
reminded health-care professionals that serious requiring safety labeling changes to the prescribing
adverse events can occur in children who are acciden- information for the class of hydroxyethyl starch prod-
tally overdosed with clonidine (Catapres® and generic ucts to amend the Boxed Warning to warn about the
brands), and even relatively minor overdoses can risk of mortality, kidney injury, and excess bleeding.
result in toxicity in young children. Clonidine is also FDA as completed a review of data and information
prescribed off label under careful medical supervision on the safety of HES products, including data from
for behavioral disorders in children with attention randomized clinical trials, meta-analyses, and obser-
deficit hyperactivity disorder (ADHD), tic disorders and vational studies. These data and information reflect
sleep disturbances. There have been 43 cases of ad- the following serious risks associated with use of HES
verse drug reactions reported to the TGA that relate to products: mortality, acute kidney injury (AKI) (includ-
overdose, incorrect dose or off-label use of clonidine ing need for renal replacement therapy (RRT), and
in children. The risk of poisoning is greater for young- excess bleeding in surgical patients who are treated
er children with low bodyweight where the low toxic with HES products; and mortality and AKI in blunt
threshold of the drug can be easily exceeded. Adverse trauma patients who are treated with HES products.
drug reactions include coma, respiratory depression, FDA has concluded that changes to the Boxed Warning
bradycardia, hypotension and hypothermia. are warranted to highlight the risk of mortality, kidney
injury, and excess bleeding, as well as to include a
Fluoroquinolones statement that HES products should not be used un-
less adequate alternative treatment is unavailable.
The Health Sciences Authority (HSA) has announced
that the use of systemic fluoroquinolones are associat- Obeticholic acid
ed with a small increased risk of heart valve regurgita-
tion. Fluoroquinolones are indicated to treat infections USFDA has announced that it has revised the boxed
such as acute sinusitis and acute bronchitis. Fluoroqui- warning for obeticholic acid (Ocaliva®) to include the
nolones are known to increase the risk of collagenre- risk of serious liver injury in patients with primary
lated disorders such as tendonitis, tendon rupture, and biliary cholangitis (PBC) and advanced cirrhosis of the
aortic aneurysm and dissection. The EMA concluded liver. Obeticholic acid is indicated to treat PBC. The
that fluoroquinolone use may increase the risk of heart FDA identified 25 cases of serious liver injury that led
valve regurgitation, and as a result the EMA recom- to liver decompensation or liver failure associated
mended that the existing warning on aortic aneurysm with the use of obeticholic acid in PBC patients with
and dissection in the package inserts of systemic and cirrhosis. The FDA believes the benefits of obeticholic
inhaled fluoroquinolone-containing products should acid outweigh the risks for PBC patients who do not
be expanded to include heart valve regurgitation. have advanced cirrhosis.

Tofacitinib Sofosbuvir

The USFDA has announced that preliminary results Health Canada has announced that they will be work-
from a clinical trial show an increased risk of serious ing with the manufacturer to update the safety infor-
heart-related problems and cancer with tofacitinib mation for sofosbuvir to include the risk of Stevens–
(Xeljanz®) use. Tofacitinib is indicated to treat arthri- Johnson syndrome (SJS). Sofosbuvir is indicated to
tis and ulcerative colitis. In 2019 the FDA warned that treat chronic hepatitis C virus infection. Health Canada
interim trial results showed an increased risk of blood reviewed the potential risk of severe cutaneous
clots and death. The FDA then requested that a safety adverse reactions (SCAR) with the use of sofosbuvir.
trial is conducted. The clinical trial is now completed This was triggered by an update to the product safety
and initial results show a higher occurrence of serious information made by the EMA. The conclusion of the
heart-related events and cancer in patients with rheu- review was that there may be a link between the use
matoid arthritis treated with both doses of tofacitinib of sofosbuvir and the risk of SJS.
compared to patients treated with a TNF inhibitor.

THE PHARMA WORLD 95

DRUG SAFETY

Cetuximab (genetic recombination) Pomalidomide, thalidomide

The Ministry of Health, Labour and Welfare (MHLW) and Health Canada has announced that the product safety
the Pharmaceuticals and Medical Devices Agency (PMDA) information for pomalidomide (Pomalyst®) has been
have announced that the package insert for cetuximab updated to include a warning of the risk of progressive
(genetic recombination) (Erbitux®) should be revised to multifocal leukoencephalopathy (PML). Health Canada
include the risk of hypomagnesaemia as an adverse drug will also include this warning in the safety information
reaction. Cetuximab is indicated to treat RAS wild-type, for thalidomide. Pomalidomide and thalidomide are
incurable, unresectable, advance/recurrent colorectal indicated to treat multiple myeloma. Health Canada’s
cancer and head and neck cancer. A total of five cases review concluded that there is a possible link between
of hypomagnesaemia have beenreported in patients pomalidomide or thalidomide and the risks of PML.
treated with cetuximab in Japan in the past three years.
Amitriptyline
Levothyroxine (tablet)
The SFDA has released a potential safety signal about
The Medicines and Healthcare Products Regulatory drug reaction with eosinophilia and systemic symp-
Agency (MHRA) has announced that the product infor- toms (DRESS) associated with the use of Amitripty-
mation for levothyroxine is being updated to include line. Amitriptyline is a tricyclic antidepressant with
the risk of aggravating thyroid symptoms when switch- sedative properties. In 2021, the SFDA reviewed all
ing between different levothyroxine products (tablets). the evidence available on the association between
From 2015 to 2019, the MHRA received 335 reports of amitriptyline and DRESS after receiving an individual
the thyroid condition being aggravated or ineffective- case safety report (ICSR). The SFDA’s investigation
ness of the levothyroxine product following substitu- concluded that the current available evidence from
tion with another. Associated symptoms were mostly assessment of the ICSRs might support a relationship
consistent with hypothyroidism or hyperthyroidism between amitriptyline and DRESS.
and included fatigue, headache, malaise, anxiety, pal-
pitation, nausea myalgia and dizziness. Theophylline

Propofol The SFDA has released a potential safety signal
concerning encephalopathy associated with the use
The Medsafe has announced that the CARM received of theophylline. Theophylline is indicated for the
a report of a patient who expressed green breast milk treatment of the symptoms and reversible airflow
post-surgery after using propofol as an anesthetic obstruction associated with chronic asthma and other
agent. Propofol is indicated for induction and mainte- chronic lung diseases. In 2021, the SFDA reviewed all
nance of general anesthesia in adults and children. It the evidence available on the association between
has been reported that propofol may discolor urine. theophylline and encephalopathy following an ICSR
Internationally, there are other case reports of green sent to the Saudi National Pharmacovigilance Centre.
breast milk following administration of propofol.

DID YOU KNOW? • Children who spend more time in extracurricu-
lar activities, like sports, and the arts, and less
• A new study has revealed that school-aged than two hours in recreational screen-based
children’s height and weight, which are indi- activities (will) have better mental health, and
cators of their health and quality of diet, vary lower levels of anxiety and depressive symp-
enormously. The study brought to the fore that toms.
variable childhood nutrition, especially a lack
of quality food, may lead to stunted growth • Just one alcoholic drink (120ml glass of wine,
and a rise in childhood obesity, thus affecting 330ml of beer or 40ml of spirits) a day was
a child’s health and wellbeing their entire life. linked to a 16% increased risk of atrial fibrilla-
tion, according to European Heart Journal.

96 THE PHARMA WORLD

REGULATORY AFFAIRS

WHO revises guidance on GMPs for
investigational products and R&D facilities

The World Health Organization are also addressed. Finally, the draft quality control, stability and technol-
(WHO) recently issued a revised guideline has sections on the qual- ogy transfer are also included in the
draft guidance to industry ad- ity unit, qualifications and validation, draft guidance.
dressing good manufacturing prac- complaints, recalls, returns, shipping
tices (GMPs) for investigational drug and destruction. The guidance includes minor re-
products as well a new draft guide- visions made after internal stake-
line addressing  GMP  principles for The WHO guidance for research holders reviewed a November 2020
research and development facilities facilities covers quality manage- version. It adds clarifies the docu-
in the context of the  COVID-19  pan- ment and quality risk management in ment’s scope and intent, noting that
demic. product research and development. “the main focus of this document is
Specific areas addressed include to provide for [good practice] in the
The guideline covers a wide scope sanitation and hygiene, qualification production and control of pre-clin-
of GMP issues including quality man- and validation, outsourced activities, ical and not for human use batches,
agement, quality risk management, self-inspection and quality audits and manufactured in pharmaceutical for-
personnel and documentation con- personnel training. Considerations mulation and development facilities,
siderations. Issues related to manu- related to premises, equipment and where these are directly supporting;
facturing premises, equipment and instruments and materials, documen- for example, shelf life claims, animal
utilities, materials and production tation, processing and process design, studies or validation activities.”

ISPE Publishes ISPE  announced  the release of its KM methods and tools enables or-
ISPE Good latest Guide, ISPE Good Practice ganizations to better manage their
Practice Guide: Guide: Knowledge Management in knowledge as a key asset, in turn
Knowledge the  Pharmaceutical Industry. The improving the effectiveness of the
Management Guide focuses on how Knowledge pharmaceutical quality system,
in the Management (KM) can enable a providing operational benefits and
Pharmaceutical more effective Pharmaceutical more.” said the Director Knowledge
Industry Quality System (PQS). Management Merck & Co Inc, Co-
Team Lead).
The first such guidance in the
pharmaceutical industry, the Guide “There are currently few re-
promotes uniting KM with Qual- sources, and no industry guidance
ity Risk Management (QRM) to en- available which address the role of
able better risk-based decisions. It Knowledge Management specifi-
shows how KM can enhance nearly cally for the pharmaceutical indus-
every element of the PQS across try. This guide works to demystify
the product lifecycle. KM and provides practical guid-
ance, templates, case studies, and
“Knowledge Management fo- references to related ISPE indus-
cuses on how organizations cre- try guidance to help organizations
ate, manage, and use knowledge better understand what KM is, the
throughout the lifecycle of a prod- benefits of effective KM, and how
uct. It, along with QRM, is one of to deploy KM” Associate Director,
the two enablers of an effective Knowledge Management,  MSD  Ire-
Pharmaceutical Quality System land (Biologics) Ltd, he added.
as defined by ICH Q10. Employing

THE PHARMA WORLD 97

IN DEPTH

Hepatitis
C kidney
transplant:
Is it possible?

Globally, an estimated  58 mil- which is the leading cause of kidney a kidney can live a regular life with
lion  people live with chron- disease and failure. their one remaining kidney, although
ic  hepatitis C. Each year, about there is a long-term risk of slightly
290,000 people die from the condition. Can people donate a kidney high blood pressure.
Although most fatalities from hepatitis if they have hepatitis C?
C are due to cirrhosis and liver cancer, When doctors remove one kidney,
doctors recognize that infection with Previously, people with HCV could not the remaining kidney compensates by
the hepatitis C virus (HCV) is also a po- donate kidneys, but this has changed increasing its blood-filtering capacity.
tential cause of kidney injury (AKI) and with the availability of direct-acting People should experience a return of
chronic kidney disease (CKD). A kid- antiviral (DAA) drugs. These drugs of- total kidney function to about 70%
ney transplant can help improve the fer cure rates above 95% for people within 10 or 11 days of donating a kid-
length and quality of a person’s life. who have contracted the virus and ney. In general, kidney donation may
also have chronic kidney disease or reduce someone’s life expectancy
How does hepatitis C end stage renal disease. by 0.5–1 year.
affect the kidneys?
Some evidence indicates that HCV- What is the impact on the person
A 2015 study of 100,518 United States positive individuals who receive kid- receiving the transplant?
veterans with hepatitis C found a link neys from HCV-positive donors have
between the condition and: slightly worse outcome than people In most cases, kidney transplanta-
who receive a kidney from HCV-negative tion  significantly improves  an indi-
l higher incidences of decreased donors. However, they have a shorter vidual’s quality of life. A person who
kidney function waiting time, which can be lifesaving. receives a new kidney may no longer
require  dialysis  and can return to
l progressive loss of kidney function Can people with hepatitis C a more normal life. However, kid-
l higher risk of death receive a kidney transplant? ney transplantation is not a cure for
chronic kidney disease, and the in-
Vasculitis due to HCV can cause AKI. Individuals living with hepatitis dividual must take medications for
In rare cases, the medications that C  can receive  a kidney transplant, the rest of their life. As a result, they
nephrologists use to treat hepatitis C but a medical team will need to may still experience some physical
can also increase the chance of AKI. consider the risks and benefits of the and mental health challenges.
However, if a person gets treatment procedure. For example, if a person
quickly, the condition usually resolves, with hepatitis C has significant liver A person’s HCV status may also af-
and the kidneys begin working again. damage, it may be unsafe for them to fect their life expectancy following a
undergo transplant surgery. However, transplant. In an earlier  2010 study,
Occasionally, HCV can also lead to if they can receive a liver and kidney doctors found that HCV-positive peo-
chronic kidney disease, which causes transplant at the same time, this may ple have a 5-year survival rate of 77%
long-term damage to the kidneys and make receiving a new kidney possible. following a transplant compared with
often deteriorates over time. This can 90% of HCV-negative patients. How-
happen due to HCV induced glomeru- Effects on kidney donors ever, this survival rate in transplant
lonephritis. This inflammation causes with hepatitis C recipients with HCV is far betters than
irreversible damage. in those who remain on dialysis.
Evidence suggests  that in the gen-
People with hepatitis C also have eral population, people who donate Source: MNT
a higher risk of developing diabetes,

98 THE PHARMA WORLD

CONCERN

Alarming antibiotic resistance killing
children in Bangladesh — Could It Spread?

Antibiotic-resistant bacteria Some 40 percent of the gram-neg- counter in Bangladesh. Most people
is causing deadly pneumo- ative bacterial infections in this study may not be able to afford to go to a
nia infections among large resisted treatment with first- and doctor, so they just go to the local
numbers of children in the South second-line antibiotics that are rou- pharmacy around the corner”. Anti-
Asian nation of Bangladesh, ex- tinely used to treat pneumonia. More biotics are handed out to treat com-
perts warn. Doctors found these alarming, children who had antibiot- mon ailments like colds and diarrhea,
«superbug» bacteria in more ic-resistant bacterial infections were which leads to “rampant antibiotic
than three of four children with 17 times more likely than others with- resistance,” he explained.
a positive blood culture for bac- out bacterial infections to die. Small-
terial pneumonia while being er studies have shown that a growing Further, a lack of safe water and
treated at a major Bangladeshi number of pneumonia cases in South poor sanitation probably exposes a
hospital, said researcher Dr. Asian countries appear to be caused greater number of children to already
Jason Harris, division chief for by bacteria resistant to antibiotics, so dangerous bacteria made even more
pediatric global health at Mas- researchers decided to look at a large deadly by antibiotic resistance, Har-
sachusetts General Hospital for group of more than 4,000 children ris added.   Comparing the problem
Children, in Boston. treated for pneumonia at the Dhaka to another current global health care
Hospital of the International Center crisis Harris said “If COVID-19 was a
The study was led by Moham- for Diarrheal Disease Research, in tsunami, then emerging antibiotic
mod Jobayer Chisti, MD, PhD, a Bangladesh. resistance is like a rising flood water.
senior scientist in icddr,b’s Nutri- And it’s kids in Bangladesh who are
tion and Clinical Services Division. “If you look at some of these anti- already going under.”
Chisti was inspired to conduct the biotic-resistant bacteria, almost none
research when he observed that of the kids survived. This is already The situation also “underscores
the hospital affiliated with icddr,b killing lots of kids in Bangladesh,” the pressing need to develop more
was admitting more and more Harris said. Widespread use of anti- antibiotics against Gram-negative
young children with pneumo- biotics in Bangladesh likely has con- bacterial pathogens and to improve
nia who were highly resistant to tributed to the rise of resistant bac- diagnostic capacity to help guide an-
treatment with standard antibiot- teria there, he noted. “Antibiotics are tibiotic selection.” Unfortunately, re-
ics. Among the children who had very commonly available over-the- search in that area has progressed at
a positive culture, gram-negative a snail’s pace.
bacteria were responsible for 77
percent of the infections, includ-
ing Pseudomonas, E. coli, Salmo-
nella and Klebsiella.

By comparison, most Ameri-
can kids stricken with bacterial
pneumonia are infected with ei-
ther  Staphylococcus  or  Strep-
tococcus, germs that usually re-
spond well to antibiotic therapy,
the researchers noted. Still, the
potential threat to people world-
wide is “kind of staggering,” Har-
ris said. “This is a good hospital
where this study was done, and
30% of the kids with bacteria in
the blood and pneumonia died,
which is unheard of. These are
lots of kids dying already.”

THE PHARMA WORLD 99

FDA UPDATE

FDA Approved Saphnelo (anifrolumab) based on the results of the pivotal Phase III FIDELIO-DKD trial
for Moderate to Severe Systemic data that demonstrated positive kidney and cardiovascular
Lupus Erythematosus outcomes in patients with CKD associated with T2D. Kerendia
works by blocking overactivation of the mineralocorticoid
AstraZeneca’s Saphnelo (anifrolumab-fnia) has been ap- receptor (MR). Mineralocorticoid receptor overactivation is
proved in the US for the treatment of adult patients with thought to contribute to fibrosis and inflammation. Fibrosis
moderate to severe systemic lupus erythematosus (SLE) who and inflammation can contribute to permanent structural
are receiving standard therapy. The approval by the USFDA kidney damage. The Kerendia label contains a Warning and
was based on efficacy and safety data from the Saphnelo clin- Precaution that Kerendia can cause hyperkalemia.
ical development programme, including two TULIP Phase III
trials and the MUSE Phase II trial. In these trials, more patients Insulin glargine-yfgn approved
treated with Saphnelo experienced a reduction in overall as the First Interchangeable
disease activity across organ systems, including skin and Biosimilar Insulin Product
joints, and achieved sustained reduction in oral corticosteroid
(OCS) use compared to placebo, with both groups receiving The USFDA approved the first interchangeable biosimilar
standard therapy. This marks the first regulatory approval for insulin product, indicated to improve glycemic control in adults
a type I interferon (type I IFN) receptor antagonist and the only and pediatric patients with Type 1 diabetes mellitus and in
new treatment approved for SLE in more than 10 years. The adults with Type 2 diabetes mellitus. Semglee (insulin glargine-
adverse reactions that occurred more frequently in patients yfgn) is both biosimilar to, and interchangeable with (can be
who received Saphnelo in the three clinical trials included substituted for), its reference product Lantus (insulin glargine),
nasopharyngitis, upper respiratory tract infection, bronchitis, a long-acting insulin analog. Semglee (insulin glargine-yfgn) is
infusion-related reactions, herpes zoster and cough. the first interchangeable biosimilar product approved in the
US for the treatment of diabetes. Approval of these insulin
Bylvay (odevixibat) in Patients with products can provide patients with additional safe, high-qual-
Progressive Familial Intrahepatic ity and potentially cost-effective options for treating diabetes.
Cholestasis Semglee (insulin glargine-yfgn), offered in 10 mL vials and 3
mL prefilled pens, is administered subcutaneously once daily.
Albireo Pharma, a rare liver disease company developing Dosing of Semglee (insulin glargine-yfgn), like Lantus, should
novel bile acid modulators, announced USFDA approval of be individualized based on the patient’s needs and should not
Bylvay (odevixibat), the first drug approved for the treatment be used during episodes of hypoglycemia (low blood sugar) or
of pruritus in all subtypes of progressive familial intrahepatic in patients with hypersensitivity to insulin glargine products.
cholestasis (PFIC). Bylvay is a potent, non-systemic ileal bile
acid transport inhibitor (IBATi), which does not require refrig- Regeneron Drug to Help Prevent
eration and is easily administered as a once-daily capsule or Severe COVID in Vulnerables
opened and sprinkled onto soft foods. Albireo is launching
Bylvay immediately to accelerate availability for the patients Even after being fully vaccinated, people with weakened im-
and families impacted by PFIC. PFIC is a rare and devastating mune systems -- including those with autoimmune diseases,
disorder affecting young children that causes progressive, life- HIV patients, cancer patients and organ transplant recipients
threatening liver disease. In many cases, PFIC leads to cirrho- -- may still be vulnerable to COVID-19. A preventive monoclo-
sis and liver failure within the first 10 years of life. Bylvay was nal antibody injection for people at high risk for developing
well tolerated with diarrhea/frequent stools being the most severe COVID-19 after exposure to the coronavirus has been
common treatment-related gastrointestinal adverse events. approved by the USFDA. Monoclonal antibodies protect
against severe COVID-19 illness by going after the corona-
Finerenone for the Treatment of virus infection while it’s still mostly in the nose and throat,
Patients with CKD Associated with T2D explained a coronavirus antibody researcher. The first dose
of Regeneron’s cocktail must be injected within 96 hours of
Bayer announced the USFDA has approved Kerendia (fi- exposure to the coronavirus, the FDA said in a statement.
nerenone), a first-in-class nonsteroidal mineralocorticoid It contains the monoclonal antibodies casirivimab and
receptor antagonist (MRA) indicated to reduce the risk of imdevimab and is the first injectable coronavirus antibody
sustained eGFR decline, kidney failure, cardiovascular death, treatment approved by the FDA to prevent COVID-19 after
non-fatal myocardial infarction (MI) and hospitalization for exposure to the virus. However, the treatment should not be
heart failure in adult patients with chronic kidney disease considered a substitute for vaccination and anyone who is
(CKD) associated with type 2 diabetes (T2D).The approval is eligible should get vaccinated, the FDA added in its approval.

100 THE PHARMA WORLD