Clinician-scientist’s Discovery Advances Fight Against Hepatitis B
A discovery by a HKUMed team identifying a target for new drugs to treat hepatitis B is nearing its goal, according to the clinician-scientist who spearheaded the finding.
In 2008, Professor Yuen Man Fung’s group found patients who had spontaneously lost a major viral protein named hepatitis B surface antigen were less likely to develop liver cancer and cirrhosis, sparking dozens of drug trials.
The physician and leading figure in the research of the liver infection hepatitis B, has since worked with almost 20 pharmaceutical companies and collaborated on up to 50 drug trials to find new treatments for the disease.
Hepatitis B is a liver disease caused by a virus of the same name. Many patients if infected in early life are unable to clear the infection, resulting in chronic hepatitis B.
Globally, around 300 million people are currently living with chronic hepatitis B. Case numbers are particularly high in Asia and Africa, with around a third of all cases found in China.
Professor Yuen, who is Deputy Department Chairperson of the Department of Medicine, graduated with a Bachelor of Medicine and Bachelor of Surgery degree from HKUMed in 1992. He subsequently achieved a Doctor of Medicine, Doctor of Philosophy, and most recently, a Doctor of Science from HKUMed.
He developed an interest in hepatitis B early in his career thanks to the high prevalence of the disease in Hong Kong. An estimated 7.2% of the territory’s population is infected with the virus.
“I saw many patients die from this dreadful disease,” he said. “And that prompted me to think I should do something or research this very important disease, because if I can find anything positive to help the patients, that will have a good impact.”
Professor Yuen stands as the top global expert in hepatitis B for journal articles published since 2013, according to expertscape, which calculates rankings based on scientific publications.
Professor Yuen has published more than 550 research articles in different medical journals. Of these, 84 were published in highly prestigious journals with an impact factor of more than 20.
A challenging virus
The hepatitis B virus is transmitted from an infected person through blood or other body fluids. It can also be passed from an infected mother to the baby during birth. Effective vaccine programmes have reduced the number of new cases in recent decades.
All hepatitis B patients should undergo regular medical monitoring. And high-risk patients are required to take daily medication to reduce the risk of developing liver cancer and cirrhosis.
Developing new treatments to tackle hepatitis B is particularly important, Professor Yuen said, as around 25 percent of infected people go on to develop liver cancer.
However, he explained that three characteristics of hepatitis B virus make treating the disease particularly challenging.
Firstly, the virus integrates with the human genome, secondly, the virus resides in the depths of the nucleus of the cell, and thirdly, the virus suppresses the patient’s immune system.
“That’s why the virus lingers on for years and years and affecting them to the stage that the patients will develop liver cancer and cirrhosis,” he said. “And that’s why at present, we still have no drugs to totally eradicate the virus from the body, unlike the other hepatitis viruses.”
World-leading discoveries
Since his decision to pursue hepatitis B research in the mid-1990s, Professor Yuen’s group has achieved a number of firsts.
In a major breakthrough more than a decade ago, his team was the first to document that patients who tested negative for a major hepatitis B surface antigen in the blood had a significantly lower risk of developing liver cancer and cirrhosis.
Spontaneous loss of this surface antigen occurs in less than 1 percent of patients each year.
This surface antigen plays a vital role in how hepatitis B suppresses the immune system, meaning that once it’s lost, the immune system is “reawakened” to fight the virus, achieving a functional cure, and removing the need for daily medication.
Following this discovery, pharmaceutical companies have sought out Professor Yuen’s expertise to help develop medicines to target the loss of this surface antigen.
He is now running trials with drug companies aiming for a 30 percent loss of surface antigen.
Initial studies over the past two years have achieved a 10–15 percent loss of surface antigen in trial participants, with higher rates in some patients, Professor Yuen said.
“I hope we can have an effective treatment that can at least achieve a 30 percent chance of functional cure in probably, I would say, three to five years from now,” he said.
His group also pioneered a predictive formula for hepatitis B patients to assess their future risk of developing liver cancer and cirrhosis.
The formula allows doctors to analyse risk factors ranging from a patient’s age and sex to their virus level and tailor their care in response.
Hope for patients
Professor Yuen describes his hepatitis B research as a lifelong task.
And despite the limited progress since hepatitis B was first identified 60 58 years ago, Professor Yuen remains optimistic that new drugs will succeed in suppressing the virus.
Alongside his own drug research, he is particularly excited to see the results of drug trials targeting the integration of the virus into the host DNA.
“If we can achieve a higher rate of cure, then we actually can cure the disease and we can remove what we describe as a horror for the liver,” he said.
