Acute-on-Chronic Liver Failure (ACLF) is one of the most severe and life-threatening liver diseases in China and the Asia-Pacific region. This complex condition arises from multiple factors, with host genetic background playing a significant role in its development, progression, and clinical outcomes. At the 2024 American Association for the Study of Liver Diseases (AASLD) conference in San Diego, a study led by Dr. Jun Li from the First Affiliated Hospital, Zhejiang University School of Medicine was recognized as a Poster of Distinction. Hepatology Digest invited Dr. Li to discuss the study’s findings, highlight key topics in ACLF research presented at the conference, and emphasize the importance of international collaboration in advancing the field.Hepatology Digest: At this year’s AASLD conference, your team’s research on biomarkers for diagnosing HBV-related ACLF received the Poster of Distinction award. Could you elaborate on the main findings and their clinical significance?
Dr. Jun Li: We were honored to have our research recognized as a Poster of Distinction at this conference. Our study revealed significant differences in the mechanisms of ACLF onset between Chinese and European populations, particularly between hepatitis B patients and Western patients with alcohol-related liver disease.
Focusing on these population characteristics, we identified the molecule SEMA6B as a critical player in the progression and outcomes of ACLF, especially in severe cases.
Through in vivo and in vitro experiments, we demonstrated that elevated levels of SEMA6B in ACLF patients, particularly those with HBV-related ACLF, were strongly correlated with poor prognosis. Patients with higher SEMA6B levels showed significantly increased mortality and were more likely to experience rapid disease deterioration or death.
Further cellular and gene knockout studies confirmed that SEMA6B activates macrophages, particularly liver-resident macrophages, prompting the release of inflammatory cytokines that drive disease progression. Our research is now nearly complete and has been accepted for publication.
We hope SEMA6B will emerge as a potential therapeutic target for ACLF treatment in the future.
Hepatology Digest: How do you view the potential of SEMA6B as a therapeutic target for improving HBV-ACLF patient outcomes? What areas need further exploration?
Dr. Jun Li: ACLF is an extraordinarily complex disease, with severe progression involving multiple mechanisms. SEMA6B is just one of these mechanisms, primarily driving inflammation through macrophage activation, which leads to hepatocyte apoptosis.
Treating HBV-related ACLF begins with antiviral therapy to address the underlying hepatitis B infection. This is often combined with additional treatments such as artificial liver support systems, small molecule drugs, and immunomodulation.
As a novel therapeutic target, SEMA6B requires extensive clinical validation before it can be translated into practical applications. Future research will need to delve deeper into the precise mechanisms of SEMA6B in ACLF and conduct large-scale clinical trials to assess its efficacy and safety.
Hepatology Digest: What were the key topics and highlights in the field of ACLF at this year’s conference?
Dr. Jun Li: There has been considerable clinical research on ACLF in the past. During this conference, we noticed a shift in focus toward the mechanisms underlying liver failure. Chinese research teams, in particular, have made remarkable progress in this area, contributing significantly to our understanding of liver failure. Many studies from China were presented at the conference, employing cutting-edge techniques such as single-cell sequencing and spatial transcriptomics. It’s evident that China’s voice is growing stronger at international conferences, with increasing global recognition.
Another pressing issue is the high mortality rate of liver failure. Developing new treatment strategies and targeting the underlying mechanisms of liver failure for precision medicine remain significant challenges.
Hepatology Digest: Could you share your reflections and key takeaways from participating in this conference?
Dr. Jun Li: With the pandemic behind us, there’s renewed enthusiasm for attending international conferences. It’s invigorating to participate in such global events.
Every year, our team actively engages in international conferences. These events provide valuable opportunities to exchange ideas with peers, learn from leading experts, and stay updated on the latest advancements. This morning, we attended a panel on ACLF in the Asia-Pacific region, where we discussed topics like fostering regional collaboration, establishing unified standards, and focusing research on specific cohorts across different countries.
During these discussions, the prominence of China’s COSSH cohort study was frequently mentioned. This study has gained considerable recognition, with many international colleagues expressing interest in data sharing and collaborative research. Following this interview, I’ll be meeting with European researchers to explore potential China-Europe collaborations.
International conferences serve as platforms for exchange and collaboration. We should make the most of these opportunities to learn from global peers and collectively advance research in ACLF.
