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近日，2024年新加坡GIHep与肝病联合大会（Combined GlHep & SHC 2024）在新加坡举办。本次会议涵盖了肝病研究的各个方面，给广大专家学者搭建了一个跨学科的交流平台。会议期间，《国际肝病》对新加坡国立大学医院Lim Seng Gee教授进行了专访，请他介绍了新加坡的肝病现状、代谢相关性脂肪性肝病（MAFLD）等相关内容。

《国际肝病》

您认为当前新加坡在肝病学领域面临的主要挑战有哪些？您的部门如何应对这些挑战？

Lim Seng Gee教授: 我的部门只负责新加坡三分之一的肝病患者，无法全面掌控整个新加坡的状况。但值得欣喜的是，在肝病领域，新加坡的不同医院在诸多常见病上展开了紧密的合作。与亚洲其他地区情况类似，新加坡最常见的肝脏疾病为乙型肝炎和非酒精性脂肪性肝病，现在也被称为代谢相关脂肪性肝病（MAFLD）。这些疾病可能导致肝癌、肝硬化合并肝衰竭等严重并发症。

我们正在探索新的治疗方法来帮助这些患者。大多数乙型肝炎患者已接受核苷（酸）类似物治疗，然而，MAFLD的治疗更具挑战性，其治疗方法刚刚问世。截至目前，最有影响力的治疗方法是GLP-1抑制剂，它有助于控制高危患者的疾病进展，尤其是合并糖尿病的MAFLD患者。

在肝癌领域，新加坡是乙型肝炎免疫治疗和肝细胞癌（HCC）新联合疗法的领导者之一。Pierce Chow教授是新加坡和亚太地区肝细胞癌临床试验的领军人物。我们在肝病领域做了很多工作，以期改善患者状况。

Hepatology Digest: What are the major challenges currently facing Singapore in the field of hepatology? And how does your department address these challenges?

Professor Lim Seng Gee: My department only looks after one-third of Singaporeans with liver disease, so we cannot control the whole of Singapore. The good news is that in the field of hepatology, we work together across different hospitals on many common conditions. Similar to the rest of Asia, the most common liver diseases are hepatitis B and MAFLD, also known as metabolic-associated fatty liver disease. These conditions can lead to complications such as liver cancer and liver cirrhosis with liver failure.

We are exploring the latest treatments to help patients in these areas. Most patients with hepatitis B are already on nucleoside analogues. The more challenging part is treating MAFLD, as treatments are just starting to emerge. The most impactful treatment so far has been GLP-1 inhibitors, which help control MAFLD in high-risk patients, particularly those with diabetes. This is starting to have a significant impact on both diabetes and MAFLD in this particular population. In the field of liver cancer, Singapore is one of the leaders in immunotherapy for hepatitis B and new combination therapies for hepatocellular carcinoma. Professor Pierce Chow is a leader in hepatocellular carcinoma clinical trials in Singapore and the Asia-Pacific region. We are doing a lot in the field of hepatology to improve the situation for our patients.

《国际肝病》

在乙型肝炎的分子生物学和免疫学研究中，您认为哪些关键发现或理论最具临床应用价值？这些发现如何帮助医生制定更有效的治疗方案？

Lim Seng Gee教授: 在乙型肝炎的分子生物学和免疫学方面，我们有一个大型的研究联盟，并且每年都会举办乙型肝炎治愈科学会议，以便及时更新最新的研究成果。要说哪个特定的发现或理论最具临床价值，这确实有些困难，因为这些会议的价值主要在于逐步深化我们对乙型肝炎功能性治愈及其内涵的理解。功能性治愈并非完全的治愈，因为患者仍然可能存在低水平的病毒复制。理解这一点以及它对患者的长期影响至关重要。分子生物学和免疫学的所有研究领域都非常重要，这也是我们的会议涵盖病毒学家、分子生物学家、临床医生、科学家以及制药公司的原因。

在制定更有效的治疗方案方面，合作是关键。例如，我们最近一次会议上的重要进展是对实现功能性治愈的患者肝活检样本进行单细胞转录组分析。这一分析揭示了这些患者肝脏环境中免疫学的变化，特别是CD4细胞毒性T细胞的增加。我们的研究焦点正在从CD8细胞转向CD4细胞，后者可能在功能性治愈过程中发挥重要作用。

此外，我们还认识到整合乙型肝炎病毒（HBV）DNA的重要性以及清除它的必要性，现有的一些治疗方法对整合HBV DNA无效。深入了解病毒学和免疫学，并在制药公司的协助下开发新药，都是我们逐步改进乙型肝炎治愈策略的重要组成部分。

Hepatology Digest: In the molecular biology and immunology research of hepatitis B, which key discoveries or theories do you believe have the most clinical application value, and how do these findings assist doctors in developing more effective treatment plans?

Professor Lim Seng Gee: For molecular biology and immunology in hepatitis B, we have a large consortium and host the Science of Hepatitis B Cure meeting annually to update the latest discoveries. It's hard to pinpoint a specific area of importance because the value of these meetings lies in the incremental understanding of achieving a functional cure for hepatitis B and what it entails. From these meetings, we have learned that a functional cure is not a complete cure, as we still see evidence of low-level viral replication. Understanding this and its implications for patients in the long term is crucial. All areas of molecular biology and immunology are important, which is why our meetings involve virologists, molecular biologists, doctors, scientists, and pharma companies.

Collaboration is essential to understanding and strategizing better treatment plans for hepatitis B. One significant advance from our recent meeting was the single-cell transcriptomic analysis of liver biopsies, revealing that the liver environment's immunology changes in patients achieving functional cure, particularly with the rise of CD4 cytotoxic T cells. We are now shifting our focus from CD8 to CD4 cells, which may play an important role in the functional cure process. We also learned about the importance of integrated hepatitis B and the need to remove it, as some treatments do not affect existing integrated hepatitis B. Understanding virology and immunology, and developing new drugs with the help of pharma companies, are all part of the gradual process of improving our strategy to cure hepatitis B.

《国际肝病》

近年来，MAFLD已成为肝病研究的热点。作为该领域的专家，您如何看待MAFLD在亚太地区当前的流行状况及其对患者健康的影响？

Lim Seng Gee教授: MAFLD并非一种单一的疾病，而是一系列具有不同风险因素的病症集合，这些风险因素包括糖尿病、高血压、高血脂、肥胖和酒精摄入等共病因素。尽管这些病症存在差异，但它们的共同特点是肝脏脂肪过多，从而导致肝脏损伤。针对不同患者群体，治疗策略也开始有所区分。近期，针对MAFLD、非酒精性脂肪性肝炎（NASH）以及减肥的新治疗方法已经获批，并在逐步推广，这有可能改变MAFLD的治疗格局。这些新药有望帮助更多人减重，从而潜在地改善或控制肥胖。不过，这些治疗方法带来的长期影响在未来几年才会显现。

当前，MAFLD的重点是进行无创检查，以便早期识别MAFLD患者，确保他们在病情恶化至肝硬化或肝癌之前得到治疗。MAFLD是一个迅速发展的领域，过去一年取得了重大进展，预计未来几个月还将迎来更多突破。随着肝病学的不断进步，我们预计每年都会涌现出新的治疗方法和策略。

Hepatology Digest: In recent years, MAFLD has emerged as a significant research focus in liver disease. As an expert in the field, how do you perceive the current epidemic status of MAFLD in the Asia-Pacific region and its impact on patient health?

Professor Lim Seng Gee: MAFLD is not a single disease; it encompasses a variety of conditions with different risk factors. There are diabetic patients, those with hypertension and high lipid levels, obese patients, and those with other comorbid factors like alcohol consumption. Despite these differences, the common factor is excessive fat in the liver, leading to liver damage. The treatment strategies for different groups are starting to diverge. Recent approvals for treatments for MAFLD, NASH, and weight loss are gaining momentum and may change the landscape of MAFLD treatment. These new drugs may help more people lose weight, potentially improving or controlling obesity. However, the impact of these treatments will not be evident for a few years.

Currently, the focus is on non-invasive tests to identify problematic MAFLD early so that patients can receive treatment before progressing to severe conditions like cirrhosis or liver cancer. This is a rapidly evolving field, with significant developments in the past year and more expected in the coming months. Hepatology is advancing quickly, and we anticipate new treatments and strategies emerging annually.