Name: Man-Fung Yuen

Institution: The University of Hong Kong

Location: Hong Kong

Email: mfyuen@hku.hk

Website/blog: http://www.medic.hku.hk/staff_...

ORCID: 0000-0001-7985-7725

Could you tell me a little bit about your research and what it entails?

I started researching liver diseases since 1995, 3 years after my graduation from medical school. My major research area is on hepatitis B virus (HBV) infection, a disease affecting more than 240 million people worldwide. Specifically, my research entails prevention of hepatitis B transmission by vaccination, human genomic predisposition to HBV chronicity and disease progression, virus genomic sequence associated with disease activity, clinical natural history of chronic HBV disease, risk factors for the development of HBV related complications i.e. HBV reactivation, liver decompensation from cirrhosis and liver cancer. Finally, I have placed enormous efforts in the development of effective treatment agents and strategies for HBV disease control.  

How did you come to be interested in viral hepatitis?

My initial interest in viral hepatitis was cultivated by my mentor, Professor Ching-Lung Lai in 1995 when he invited me to join the research team of Hepatology. He introduced HBV to me by posing me a simple question, i.e. “What kind of disease is highly prevalent in Asia with long-term detrimental outcome and at the same time of global interest and importance?” HBV is obviously of this particular category. I later found out that because of the high complexity of this chronic viral infection, the research on this disease would not end with my academic career. The most intriguing thing is the different outcomes of the disease resulting from interaction between different host and the virus factors. This leads to different lines of thoughts embedded in different research studies and opinions from researchers.

What do you see as the biggest accomplishment in your field in the past few years?

New knowledge on HBV disease has been continually deciphered from the day of HBV discovery. Over the past 10 to 15 years, the natural history of HBV disease has been more accurately defined. This has a tremendous impact on the treatment decision for the patients. Reduction in the development of HBV-related end-staged liver diseases and liver cancer are now achievable. Over the past 5 years, studies have identified reliable parameters from which one can predict the risk of development of complications accurately. Patients can be classified into low to high risk groups. At the same time, two first line nucleos(t)ide agents (entecavir and tenofovir) have been well accepted and adopted worldwide. Increasing drug prescription to control the disease have already achieved a reduced incidence of disease morbidity and mortality in many countries. Long-term viral suppression through long-term treatment has become more acceptable to most clinicians and patients, although the functional cure defined by HBsAg seroclearance is getting more attention as an endpoint of therapy. Over the past 2 years, novel agents acting against different viral replicative pathways have been under active investigations. They include core protein assembly modulators, short interfering RNA, selective immune modulators activating specific cellular proteins within infected cells, as well as viral particle release inhibitors. Initial promising inhibitory effects on the different viral components have been encouraging. 

What do you see as the main challenges for research in your field in the coming years?

There are a few main challenges for HBV research in the coming years. Firstly, we need to investigate and select the best drug(s) among the several novel agents acting on different steps of viral replication in addition to the inhibition of reverse transcription which had been successfully achieved for many years. This would be followed by the research for the best strategy and combination of agents to enhance the disease control. Secondly, we need to explore the viral mechanistic details and identify host and viral factors for the development of cirrhosis and liver cancer even with adequate suppression of viral replication. Finally, agents are being actively explored for degradation of the viral template covalently closed circular (ccc) DNA for the HBV. This, if achievable, would result in the final goal of HBV eradication.

What personal career achievement are you most proud of? Why?

With the long and untiring efforts on HBV research, my research results had widely been accepted in the field. They have made important impact on defining the natural history and the treatment of the disease. More importantly, our findings have become major considerations for international recommendations and guidelines for the disease management. I am particularly proud of the output of my research team which has performed innumerable research studies in spite of the very scanty research supports in my locality.