Editor’s Note: The 74th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2023) has just concluded in Boston, USA. The team led by Professor Wai-Kay Seto from the University of Hong Kong focused on five research outcomes in the areas of mother-to-child transmission blockage and clinical cure of Hepatitis B, clearance of Hepatitis C, post-operative recurrence of liver cancer, and post-liver transplant management. These outcomes were presented at the meeting, with two of them being shared in the form of oral presentations. Professor Seto’s team has been committed to the clinical management and scientific research of chronic liver diseases, achieving fruitful results. Hepatology Digest invited the team’s principal researchers to interpret the findings and comment on the trends in liver disease research and share their experiences at the conference. The interview video is shared below.
Interpretation of the Five Research Outcomes:
1. Postpartum Outcomes for Mothers and Infants Following Immediate Discontinuation of Tenofovir Disoproxil Fumarate (TDF) in Women with High Viral Load Chronic HBV Infection
Hepatology Digest : First, congratulations to your team for having five research outcomes selected for presentation at the conference. One of the oral presentations discussed the mother-to-infant outcomes following immediate postpartum discontinuation of Tenofovir Disoproxil Fumarate (TDF) in women with high viral load chronic HBV infection. The results suggest that immediate cessation of prophylactic TDF post-delivery showed similar rates of virological relapse or retreatment compared to discontinuing TDF four weeks postpartum [1]. Could you share the background or motivation behind this study, as well as the significance of these findings?
Professor Wai-Kay Seto: Our primary focus was to observe the clinical outcomes of pregnant women with high viral loads of Hepatitis B who were preventively treated with Tenofovir Disoproxil Fumarate (TDF) during pregnancy, and their situation postpartum regarding medication discontinuation. Conducting this study during the COVID-19 pandemic posed significant challenges.
From the 330 patients we included, the timing of medication discontinuation postpartum, whether immediately after delivery or four weeks later, did not significantly impact their virological status postpartum (Figure 1). Previously, it was believed that viral loads would increase and 80% would relapse after stopping the medication postpartum, but we only observed a rise in transaminase levels in about 20% of cases. Therefore, most pregnant women can feasibly take TDF preventively and stop postpartum, but monitoring is important. Additionally, the study showed that preventive use of TDF for mother-to-infant transmission blockage was successful, as none of the newborns were infected with HBV, indicating the effectiveness of TDF for most pregnant women with Hepatitis B.
2. The Multimodal Deep Learning Model RECURR-NET for Predicting Recurrence of Hepatocellular Carcinoma Post-Curative Surgery Outperforms Microvascular Invasion (MVI): Results of Internal and External Validation
Hepatology Digest : Another oral presentation shared the internal and external validation results of the RECURR-NET model in predicting post-curative surgery recurrence of Hepatocellular Carcinoma (HCC) [2]. Could you discuss the development process of this model and its potential applications?
Dr. Rex Wan-Hin Hui: This artificial intelligence research was completed under Professor Seto’s leadership, involving both physicians and computer engineers. A major challenge in the field of liver cancer is the common recurrence of tumors post liver resection. Therefore, our initial goal was to see if there was a better method to predict the recurrence of liver cancer in patients.
Previously, predictions were commonly based on clinical judgment or histological markers in the resected tissue. However, our study explores the use of computer tomography (CT) scans to predict HCC recurrence, combining it with patient data to develop an artificial intelligence prediction model. The results show that the RECURR-NET artificial intelligence system can effectively predict post-curative surgery HCC recurrence in both internal and external validation cohorts and can determine if a patient is likely to die shortly. Therefore, we believe this system has the potential to assist in clinical decision-making in the future, such as determining whether patients need other treatments before surgery.
Professor Wai-Kay Seto: Artificial intelligence is increasingly being used in clinical settings, but has traditionally been used in a unimodal context, like in radiology to increase diagnostic rates, or in pathology. However, our study can be used in a multimodal context, like combining radiological modalities with clinical data for analysis, which is a unique aspect of our research.
3. The Ratio of Alanine Aminotransferase to Quantitative HBsAg Independently Predicts Long-term HBsAg Serological Clearance in Chinese Hepatitis B Patients after Discontinuation of Entecavir
Hepatology Digest : Regarding chronic Hepatitis B (CHB) patients inducing Hepatitis B surface antigen (HBsAg) serological clearance by discontinuing nucleos(t)ide analogs [3], your team also introduced related progress. Could you discuss the findings and their implications for future research and clinical management?
Dr. Rex Wan-Hin Hui: The patients in this study were from two studies conducted by Professor Seto in 2015 and 2021. We followed these patients long-term to observe their clinical outcomes. They were all treated with antiviral therapy using Entecavir (ETV) before stopping medication and were continuously followed up until 2023. Currently, we see that a portion of the patients has achieved HBsAg clearance, which is a good outcome. However, predicting whether HBsAg will disappear after stopping medication has long been unclear.
Previous researchers found that HBsAg quantification levels could be used for prediction, but an accurate method has not been found to date. Our study used the ratio of ALT to quantitative HBsAg to predict HBsAg clearance after stopping medication. The results showed that measuring the ratio at different times, from the time of stopping medication up to 48 weeks afterwards, could effectively predict patients likely to achieve HBsAg serological clearance. We hope this new ratio prediction method can be used in more patients in the future.
4. MRI-PDFF and MRE Techniques for Assessing Fatty Degeneration and Fibrosis in Liver Transplants Post-Surgery
Hepatology Digest : Regarding fatty degeneration and fibrosis in liver transplants post-surgery, your team analyzed the MRI-PDFF and MRE assessment methods [4]. Could you introduce the study results and your recommendations for clinical practice?
Dr. Lung Yi Mak, Clinical Assistant Professor at the University of Hong Kong Faculty of Medicine, member of the State Key Laboratory of Liver Research at the University of Hong Kong, internist at Queen Mary Hospital, Hong Kong, editor at Frontiers in Microbiology and Hepatology Communications
Dr. Lung Yi Mak: This study was a collaboration between the internal and surgical departments of the University of Hong Kong. We know that in China, including Hong Kong, only a small portion of patients undergo liver transplants due to fatty liver disease, but the incidence of fatty liver after transplantation is not low. So, we wanted to use MRI to assess the post-transplant liver fat content and fibrosis, and to quantify the incidence of new-onset fatty liver in patients who underwent transplantation for non-fatty liver indications in the Hong Kong region.
The results showed that among 293 patients, the incidence of new-onset fatty liver reached 30%, and severe liver fibrosis occurred in one out of every ten patients; patients with new-onset fatty liver often had metabolic dysfunctions and transplant liver dysfunctions. Additionally, we compared the differences in assessing liver fat content and fibrosis between Transient Elastography (TE) and MRI techniques. The results showed that TE was more accurate for assessing the right lobe and upper segments of the liver.
Overall, our study suggests that regardless of whether patients undergo liver transplantation for fatty liver, considering the incidence of fatty liver, non-invasive assessment methods should be used to monitor the development of fatty liver post-transplantation.
Professor Wai-Kay Seto emphasized the importance of controlling high-risk factors after liver transplantation. It was observed that using a more precise method, namely magnetic resonance imaging (MRI) for quantifying fatty liver, 30% of patients developed fatty liver after transplantation. Thus, transplantation does not mean all problems are resolved; it is also necessary to control metabolic risk factors.
5. Conquering Hepatitis via Micro-Elimination (CHIME) Program for Chronic Hepatitis C Infection in High-Risk Populations in Hong Kong: Final Results
Hepatology Digest : The last poster presented the final results of the Conquering Hepatitis via Micro-Elimination (CHIME) program for chronic hepatitis C in high-risk populations in Hong Kong [5]. Could you discuss these results and share your views on the micro-elimination program? Do you recommend its nationwide implementation?
Dr. Lung Yi Mak: Hepatitis C is not common in the general population in Hong Kong, but we know it has a high prevalence in high-risk groups, such as those who inject drugs. Our team arranged an outreach team to visit halfway houses and drug rehabilitation centers, providing health education and helping with hepatitis C screening.
We found a high infection rate of 47% for the hepatitis C virus. We invited these patients to nursing contact clinics for assessment and treatment, but 30% of the patients did not visit the clinic. After evaluating these patients, we provided a one-time pan-genotypic direct-acting antiviral medication, and the results showed that over 90% of the patients could be completely cured.
Thus, our study indicates that the micro-elimination program is feasible and effective and should be further applied and promoted in other regions of China.
Professor Wai-Kay Seto: Regarding hepatitis C elimination, it is important to emphasize that the concept of “micro-elimination” targets specific populations, not mass screening. Our study in Hong Kong was focused on a special group with a history of drug use. In exchanges with scholars from mainland China, I learned that different regions in mainland China also have screening for groups with a history of drug use, and the positivity rate is very high, often over 50%. Therefore, if we aim to achieve hepatitis C elimination, a micro-elimination strategy targeting high-risk groups is necessary to achieve the elimination goal.
Commentary on Liver Disease Research Trends and Sharing Conference Experiences
<Hepatology Digest>: Finally, could you share the topics or advancements at this AASLD meeting that impressed you the most? And your takeaways or feelings from the trip?
Professor Wai-Kay Seto: Over the years, the AASLD annual meeting has consistently presented the latest research advancements in the field of liver diseases, such as viral hepatitis (Hepatitis B, C, and D), as well as fatty liver, cirrhosis, complications of cirrhosis, and various studies on liver cancer. Compared to previous meetings, this year’s focus was on fatty liver, as new drugs for fatty liver are expected to come to market in the coming years.
Moreover, I felt that the meeting also placed more emphasis on liver cancer, with many new drugs promising breakthroughs in complex liver cancer treatment. Additionally, muscle wasting syndrome, a complication of cirrhosis that was previously less focused on, is now receiving more attention, highlighting the importance of nutritional support in the management of patients with cirrhosis.
Dr. Lung Yi Mak: I completely agree with Professor Seto. I noticed that the proportion of reports on fatty liver has increased significantly compared to the past. Also, I observed more attendees from Asia than in previous meetings, which is great as it allows for the exchange of different opinions and hopefully leads to more collaboration in the future.
Dr. Rex Wan-Hin Hui: In recent years, there have been significant advancements in clinical trials of new drugs in the field of liver diseases, with potential new drugs coming to market or major research breakthroughs expected soon. The AASLD meeting was very insightful, and I learned a lot of new knowledge from experts from different countries and regions. I hope to continue working hard and achieve new breakthroughs after returning.
References:
[1] Yu C, Mak LY, Tang M, et al. Immediate postpartum cessation of tenofovir in highly viremic pregnant mothers with chronic hepatitis B infection: maternal and infant outcomes. AASLD 2023. Oral 59.
[2] Hui RW, Chiu K, Lee IC, et al. RECURR-NET, a multiphasic deep learning model, is superior to microvascular invasion in predicting hepatocellular carcinoma recurrence after curative surgery: results from internal validation and external testing. AASLD 2023. Oral 90.
[3] Leung RH, Hui RW, Mak LY, et al. Alanine aminotransferase to quantitative HBsAg ratio independently predicts long term HBsAg seroclearance after entecavir cessation in Chinese Hepatitis B patients. AASLD 2023. Poster 1492-C.
[4] Mak LY, Fung J, Lo G, et al. Detection of hepatic graft steatosis and fibrosis after liver transplantation using MRI-PDFF & MRE techniques. AASLD 2023. Poster 1065-A.
[5] Mak LY, To WP, Tsui V, et al. Conquering Hepatitis via MICRO-ELIMINATION (CHIME) program for chronic hepatitis C infection in high-risk populations in HONG KONG: final results. AASLD 2023. Poster 1818-A.
Expert Profiles
Professor Seto Wai-Kay, M.D., Chief Physician, currently serves as a Clinical Professor in the Department of Medicine, Gastroenterology and Hepatology at the University of Hong Kong, a principal researcher at the State Key Laboratory of Liver Research (University of Hong Kong), and is in charge of Gastroenterology at the University of Hong Kong-Shenzhen Hospital.
