长江之滨 中外对话丨专家高端会谈，探索病毒性肝炎研究的前沿与合作路径

我认为这是一个非常重要的问题，可能所有临床医生都想知道答案。但我同意Kennedy教授的观点。在治疗方面，至少从我的了解来看，暂时还没有一个重大的突破性的药物能够进入临床实践。然而，我们确实在基础研究和临床试验方面取得了许多进展。关于新的治疗靶点，我认为仍然分为两类：抗病毒药物，即直接作用抗病毒药物（DAAs），以及免疫调节治疗。

我们已经看到了许多新药的Ⅰ期、Ⅱ期临床试验，甚至部分已经进入了Ⅲ期临床研究。因此，我们期待随着新药的不断研发和临床试验的推进，将会带来更多有说服力的数据，不久的将来可能会有更多有效的治疗手段进入临床实践。我们在慢性乙型肝炎自然史以及功能性治愈优化治疗策略和管理路径方面已经有了深入的理解。最近，我组织了包括Kennedy教授、袁教授以及来自亚太地区、欧洲和美国的多位专家对功能性治愈路线图进行了更新。在更新版专家共识中，我们在慢性乙型肝炎自然史、功能性治愈治疗策略以及可能在不久的未来进入临床的新药方面进行了全面的更新。

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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?

我完全同意Kennedy教授的观点，新型标志物在评估患者状态和监测治疗应答发挥关键作用。但我想就这一重要话题再补充一点。事实上，在我国国家重点研发计划中一个重要的研究目标，是研究和开发临床实用且简单易行的免疫检测方法，用于准确评估患者的免疫状态。这正是我们全国重点实验室承担的国家重点研发计划以及我所在部门目前正在积极推进的重点工作之一。我认为Kennedy教授在本次会议上提出的问题尤为关键。

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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.

我完全赞同Kennedy教授的观点。然而，中国的肝病研究团队与世界其他地区相比有一定的区别。在我国的医学体系中，大多数管理病毒性肝炎患者的临床医生属于传染病科，而这个科室相对于内科或外科等其他科室来说规模较小。因此，我们必须积极寻求与其他科室和医生的合作。同时，国际交流与合作也是不可或缺的。我们最近深刻体会到，与人工智能科学家的合作对于提高大数据管理的敏感性和特异性至关重要。我们通过APASL、EASL和AASLD等国际肝病学会开展的国际交流与合作对于我们来说非常重要，我们之间的合作交流已经超过15年。

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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.

没错。我们目前面临的一个重大挑战是，在慢性病毒性肝炎合并脂肪肝的患者的抗病毒治疗领域尚未形成统一的共识和指南，因此需要进一步深入研究，为这些患者抗病毒治疗策略的制定提供更多的证据。