Hep to a Cure

Chronic hepatitis B infection can remain asymptomatic for decades, yet left untreated, it can cause severe damage to the liver and lead to life-threatening conditions such as cirrhosis and liver cancer, the third leading cause of cancer deaths in Hong Kong. About 410,000 people in Hong Kong carry the hepatitis B virus, as do more than 257 million globally. The World Health Organization (WHO) has called for its elimination by 2030.

A key contributor towards achieving that goal is Professor Yuen Man-fung, Chair Professor of Gastroenterology and Hepatology, and Li Shu Fan Medical Foundation Professor in Medicine.

Professor Yuen is the top hepatitis B researcher in the world, according to Expertscape based on publications between 2013 and 2023. He was one of the first in the world to develop a risk score for hepatocellular carcinoma in hepatitis B patients.

He also identified a treatment target by showing patients who spontaneously lost the surface antigen of the virus before the age of 50 had a significantly lower chance of developing serious liver disease.

That discovery led to the development of a new drug, bepirovirsen, that is undergoing a phase three clinical trial in centres around the world and offers hope of a cure for at least some patients. He is also investigating other treatments, including a promising combination of antiviral and immunomodulatory agents, and he has helped develop outreach programmes to offer testing and treatment in the community.

“We want to align with the WHO goal of eliminating hepatitis B in the world by 2030. Although this may take a few years longer, at least we need to move in that direction to diagnose and treat patients and decrease mortality related to viral infection,” he said.

Promising early results

Bepirovirsen already showed in a phase two trial that it could functionally cure 10 per cent of participants, who had undetectable surface antigen of the virus after six months – this is 10 times higher than occurs naturally. Professor Yuen said they aim to push that rate to as high as 30 per cent within the next couple of years, meaning such patients would no longer need to take drugs every day for the rest of their lives to control the virus.

But even with that promise, there is the problem that people often do not know they carry the hepatitis B virus until their liver is damaged – the virus sometimes does not show up on standard blood tests.

Professor Yuen is therefore also working to improve detection of these hidden or ‘occult’ cases. He is collaborating on a project that has increased the diagnostic rate of occult hepatitis B infection from less than 20 per cent to 67 per cent.

He has also recently completed a study that confirmed the hepatitis B virus can integrate with a person’s DNA, so even if all viable traces of the virus are killed off in a person’s liver, the liver cancer process can still be triggered because the virus remains in their DNA.

“The integration process actually starts early in a person’s lifetime, so we want to emphasise that we need to treat patients as soon as possible – when they are in their 20s or 30s – rather than wait for other indications. Some experts say we should wait until the virus reaches a certain level in the blood before treatment, but we believe it should happen before the integration process becomes more entrenched. Theoretically, this would decrease the chance of developing liver cancer,” he said.

Combatting hepatitis C, too

An important factor in doing that is to make sure people are aware they are hepatitis B carriers. According to Hong Kong’s Department of Health, nearly 40 per cent of hepatitis B carriers are unaware of their condition. “They think they are fine, they have no symptoms, so therefore they are not hepatitis B patients. But this is not true,” Professor Yuen said.

He recently teamed up with the Hong Kong Liver Foundation to bring testing into the community through a mobile truck that will spend the next five years travelling to each of Hong Kong’s 18 districts to test people for the virus and make referrals if treatment is needed.

He has also been involved in programmes to treat another life-threatening infection, hepatitis C, in vulnerable populations. In one programme, he worked with different NGOs to screen and treat nearly 400 former intravenous drug users.

More recently, he has been working with the Correctional Services Department, the Hospital Authority and the Chinese University of Hong Kong in a programme focussed on prisoners. They are tested at prison and can receive treatment there, too. “Hepatitis C can be cured with a few months of treatment but if untreated, it will also cause liver damage,” he said.