A research team from Aga Khan University has received a grant to conduct a clinical trial to evaluate if the drug Granulocyte Colony Stimulating Factor (GCSF), commonly used for cancer treatment, will help increase bile secretions for obstructive jaundice in children requiring surgery.
The jaundice, biliary atresia (BA), results when a baby’s bile duct is blocked and the flow of bile (secretion from the liver for fat digestion) is reduced. The accumulating bile causes damage and cirrhosis in the organ ultimately resulting in liver failure. If left unoperated, the jaundice is lethal with an average survival of 10 months. An estimated 80 million children in Pakistan are affected by BA and in event of shortage of paediatric liver transplants, the disease largely remains untreated.
The surgery, Kasai portoenterostomy, provides children a window of survival for two to three years until the transplant takes place. “Due to the limitations of this surgery (as it is only a temporary bypass), liver transplants remain the only long-term solution,” said Sohail Dogar, a senior instructor in the department of surgery and a member of the team conducting the clinical trial. Additionally, Kasai is unable to address the problem of declining liver function. The outcome and management of patients who did not opt for transplants remains unimproved in the last 45 years, according to the research team.
The drug GCSF has been tested for treating liver sufficiency and previous short-term clinical studies show that it is not only safe but very effective in improving liver function in adult chronic liver diseases.
In Kasai portoenterostomy, bile ducts are cut and a loop of small intestine is brought into the liver tissue to facilitate bile draining. The GCSF drug, on the other hand, is an affordable, non-intervening alternative for patients to opt for until they eventually decide to undergo a liver transplant procedure.
The AKU team is working in conjunction with the University of Illinois and national hospital centres in Vietnam to target 218 people in the clinical trial spanning three years. The collected data from the three centres will be then synthesised.
The drug GCSF is available in Pakistan and is used for cancer treatment but not for BA indication in children. “GCSF is used for adult liver sclerosis patients around the world and has very promising results. This is where the idea perform a trial on children by administering dosages accordingly first originated,” said Dr Saqib Hamid Qazi, an assistant professor and paediatric surgeon at the University and the lead researcher in the study.
The research team is hopeful that GCSF will not only help with liver repair but reduce inflammation and fibrosis. One of the aims of the clinical trial is to look at short term outcomes and assess whether bile secretions improve in patients who may or may not have undergone surgery.
The research and clinical trials will work towards achieving target 3.4 of the sustainable development goals which seeks to reduce premature mortality from non-communicable diseases like liver cirrhosis by a third by 2030.
AKU researchers are of the view that the clinical trial will not only help people but is a step towards revolutionising healthcare.
“We are providing the most vulnerable part of the society with a very suitable, cost-effective treatment to a cause of severe morbidity and mortality,” said Abeer Aziz, a research associate with the provost’s office.
The research team includes Dr Saqib Hamid Qazi and Dr Jai Das from department of paediatrics and child health, Dr Sohail Asghar Dogar and Abeer Aziz, senior instructor and research associate from department of surgery, respectively.