Editor's note: The Mid-Autumn Festival, a traditional Chinese festival, has just passed. Many experts and scholars in the field of infectious diseases and liver diseases from home and abroad gathered in Wuhan, the capital city of Hubei Province, to attend the Annual Congress of State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases 2024 s and Central China International Forum on Liver Disease and Infection(CCIFLDI 2024), a grand event in the field of infectious diseases. This conference set up multiple topics to discuss clinical hotspots and difficult issues from different perspectives. During the conference, the editorial department of Hepatology Digest invited Dr. Qin Ning from Tongji Hospital and Dr. Patrick T.F. Kennedy from Queen Mary University of London to conduct in-depth discussions on issues such as viral hepatitis and international cooperation.Hepatology Digest：Both of you have made remarkable achievements in the research field of hepatitis virus infections. May I ask what are the breakthrough discoveries regarding new therapeutic targets for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections? What is the significance of these findings for clinical treatment?
Patrick T.F. Kennedy：First of all, thank you for the invitation and thank you for the question. I think we are seeing progress in the field of chronic hepatitis B, but I think we are maybe not quite at a point where I could say there’s been a major breakthrough. I think every year at the international liver meetings, we’re seeing new data which adds bit by bit towards the achievement of functional cure. But we, as physicians—both myself and Professor Ning, I’m sure—would like to have seen more progress than where we are now. And that underlines the work that still needs to be done to achieve functional cure.
So, will that be around certain combinations of strategies, be that antiviral or immunomodulatory agents, how they’re combined, and the timing of combination? Maybe patient selection is also an important area. So, while we recognize that there has been a lot of progress, we also recognize that there is a lot of work to be done. For us to do that, I think it will require a broad kind of collaborative approach in terms of how we approach clinical trials and not just the clinical trials but maybe some of the sub-studies around virology, immunology sub-studies, which will inform the progress and hopefully give us the direction to achieve functional cure.
Qin Ning：Thank you very much for the question. I think this is quite an important question that probably all the clinicians would like to ask. But I agree with Professor Kennedy. In terms of treatment, I think, at least from my knowledge, there has not been a major breakthrough that has come into clinical practice. However, it is true that we have seen many, many progresses in terms of basic research as well as clinical trials. So, regarding the new therapeutic targets, I think there are still two classifications: antiviral, directly acting antivirals (DAAs), as well as immune modulation.
We’ve seen many, many clinical trials in phase one, phase two, and some of them are even going into phase three. So, we are actually expecting more convincing data that could, in the near future, come into clinical practice. However, we do have tremendous understanding in terms of the natural history of the patients, as well as how to manage these patients to reach the endpoint of functional cure. So, recently, I, Professor Kennedy, Professor Yuan, and many experts from the Asia-Pacific region, as well as from Europe and the United States, we have updated the previous version of the roadmap for the functional cure. In this new version of the functional cure consensus, I think we have updated tremendous knowledge in terms of the natural history, the treatment strategies, and particularly the new potential agents that may be put into clinics in the near future.
Hepatology Digest : Professor Kennedy, you presented a keynote speech titled “Utility of Novel Virus and Immune Markers in Predicting HBV Treatment Endpoint” at this conference. Could you please briefly introduce it？
Patrick T.F. Kennedy：Yes, thank you. So, my presentation today was about the utility of novel viral and immune markers in determining treatment endpoints. And to pick up on what Professor Ning was saying, that presentation really highlights a lot of the progress that we’ve made in the field. So, it highlights the use of novel virological markers, for example, that we didn’t have maybe five or seven years ago. It highlights the progress that we are making in terms of immunological markers, in terms of better definition of disease and better definition of host immune responses and control.
So, these are really key elements in terms of predicting where we will go with treatment and with treatment endpoints and hopefully achieving functional cure. But again, more broadly, treatment endpoints are about where we can stop treatment, ideally, and the patient is safe, meaning there’s no disease progression or development of hepatocellular carcinoma (HCC). We need to be very clear that our patients are in the safest possible place before we start to determine that treatment can be stopped or not.And that is also about the prevention of dose sequelae, progression of disease, and development of liver cancer.
So, I would say my presentation today was highlighting the progress we’ve made around new novel virological markers, the progress we’ve made around immunological biomarkers, and the utility of these to help us one: develop that roadmap that Professor Ning is talking about to achieve functional cure, but also to inform patients and physicians about where it’s potentially feasible to stop treatment—where they will be safe, and there will be no disease progression or consequences of chronic hepatitis B. So, this work is equally important as the work around the development of novel agents to achieve a cure because we need the parameters and the tools to understand the disease and understand where patients will be in terms of treatment outcomes.
Qin Ning：Yes, actually, I want to add one point to this important topic. I think I fully agree that the parameters to evaluate the patient’s status, as well as to monitor the treatment response, are one of the key issues. In fact, one of the important projects among all national projects in China is to study, to investigate, and possibly make significant progress in developing clinically practical and easy-to-use parameters for immune assays—immune status assays—for these patients. This is one of the projects that we are undertaking in our national key laboratory, as well as in our department. I think Professor Kennedy brings up very, very key issues in this conference.
Hepatology Digest : In terms of interdisciplinary collaboration, which areas of collaboration do you both consider most important for advancing research and treatment of hepatitis virus infections, liver fibrosis, and fatty liver?
Patrick T.F. Kennedy: Yes, I think we all recognize the complexity of managing chronic hepatitis B, and we’ve just talked about the complexity of trying to achieve a functional cure. So, I think both Professor Ning and I definitely understand the importance of collaboration, the exchange of ideas, and sharing approaches to improve diagnostics, therapeutics, and ultimately achieve functional cure. Personally, I see very strong benefits in working closely together, sharing research on different populations—whether Chinese patients, European patients, or African patients who have migrated to Europe.
I believe that we won’t achieve the progress we want to make without working in a collaborative way to better understand the disease, individual patients, and the different approaches we can offer them.
Qin Ning: Yes, I entirely agree. The liver disease study group in China is a bit different from other parts of the world. Most viral hepatitis clinicians are part of the Infectious Diseases Department, which is relatively small compared to other departments, like Internal Medicine or Surgery. So, we must be strong and collaborate with other departments and doctors. Also, international exchange and collaboration are essential. We’ve recently realized the importance of collaborating with AI scientists to increase sensitivity and specificity in large data management. This international exchange, as we’ve been doing through organizations like APASL, EASL, and AASLD, is crucial, and we’ve known each other for over 15 years.
Hepatology Digest : May I ask, professors, what role does collaboration play in the research and treatment of hepatitis and other liver diseases? How is the importance of collaboration manifested?
Patrick T.F. Kennedy: Yes, exactly. I think as physicians and physician-scientists, we understand the importance of collaboration in securing grant funding, sharing ideas, and having team members work across different regions. For instance, metabolic liver disease, in addition to hepatitis B, is becoming more common. Understanding how this differs in China versus Europe or the UK is crucial, and collaboration is key to addressing these challenges.
Qin Ning: Exactly. One of the areas where we don’t yet have a consensus or guidelines is in the treatment of patients with chronic viral hepatitis and coexisting fatty liver disease. We need more studies to provide evidence supporting antiviral treatment strategies for these patients.
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