Editor's note: Recently, the Combined GlHep&SHC 2024 was held in Singapore. This conference covers various aspects of liver disease research and provides an interdisciplinary communication platform for experts and scholars. During the conference, Hepatology Digest conducted an exclusive interview with Professor Lim Seng Gee from the National University Hospital of Singapore, asking him to introduce the current status of liver disease in Singapore, metabolic associated fatty liver disease (MAFLD), and other related topics.Hepatology Digest: What are the major challenges currently facing Singapore in the field of hepatology? And how does your department address these challenges?
Dr 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.
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?
Dr 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.
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?
Dr 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.
