During the recently concluded 75th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), we had the privilege of conducting an in-depth interview with Dr. Jiangao Fan from the Department of Gastroenterology at Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine. Dr. Fan highlighted that the latest drug development efforts are now focusing on metabolic dysfunction-associated steatohepatitis (MASH), particularly cases involving significant liver fibrosis. The research trend is shifting from addressing downstream liver damage to targeting liver oxidative metabolism and promoting systemic weight reduction. Lifestyle changes remain at the heart of therapeutic strategies, profoundly influencing interventions for liver inflammation and fibrosis. Professor Fan also shared his team’s recent breakthroughs in metabolic dysfunction-associated fatty liver disease (MAFLD) research. Below is the detailed account of our discussion for our readers.Key Advances and Trends in MAFLD at AASLD 2023
Hepatology Digest: What are the latest developments and trends in MAFLD research presented at this year’s AASLD?
Dr. Jiangao Fan: The AASLD annual meeting continues to stay ahead of the curve, addressing the pressing needs of public health and clinical care. In the field of MAFLD, topics ranging from the underlying mechanisms and clinical diagnostics to risk stratification and non-invasive assessment tools have taken center stage. The spotlight is undoubtedly on drug development, which remains a focal point of this year’s discussions.
This year’s meeting also emphasized metabolic and alcohol-associated liver disease (MetALD), delving into the complex interplay between alcohol consumption, nutrition, energy excess, and liver disease progression. This is just the beginning. A dedicated conference titled “MAFLD, MetALD, and Alcohol-Related Liver Disease (ALD): Challenges and Opportunities” is scheduled for February 2025 in Las Vegas, promising to further explore these novel liver disease paradigms and offer tailored clinical strategies.
In drug development, the primary focus has shifted towards addressing MASH cases with liver fibrosis. Unlike earlier approaches that primarily targeted liver cell apoptosis or inflammation, current research is zeroing in on oxidative metabolism and systemic weight management, stepping beyond traditional antifibrotic treatments. This evolution reflects a deeper commitment to tackling the root causes of metabolic dysfunction, paving the way for innovative therapies that address glucolipotoxicity-induced inflammation, liver damage, and fibrosis.
It’s worth noting that while the selective thyroid hormone receptor beta (THRβ) agonist approved by the U.S. FDA in March 2023 has garnered significant attention, its clinical efficacy remains modest. Furthermore, concerns about potential side effects, including drug-induced liver injury, warrant careful consideration.
Focus Areas and Key Takeaways
Hepatology Digest: What aspects of this year’s conference did you focus on, and which research stood out to you the most?
Dr. Jiangao Fan: Lifestyle interventions are pivotal in managing MAFLD, MetALD, and ALD. These changes profoundly impact liver inflammation and fibrosis outcomes. For instance, in alcohol-associated hepatitis with fibrosis, reducing or ceasing alcohol consumption plays a crucial role in mitigating inflammation and enhancing the efficacy of drug therapies.
In fact, all drug development efforts rely on a foundation of lifestyle improvements by patients, supplemented by pharmacological interventions. Future drug trials must consider placebo-controlled designs alongside detailed stratification of patients based on their adherence to lifestyle modifications. Quantitative scoring of lifestyle changes, similar to evaluating alcohol reduction in ALD patients, is crucial as it directly correlates with treatment outcomes.
At this year’s AASLD, I had the honor of participating in the Global MASH Expert Panel discussion, which focused on drafting guidelines for lifestyle modifications. Key topics included alcohol moderation, healthy dietary practices, and increased physical activity for patients with MAFLD and MetALD. These foundational measures are essential for achieving optimal clinical outcomes.
Research Highlights from Professor Fan’s Team
Hepatology Digest: Could you share your team’s contributions to this year’s AASLD meeting? What are the key findings and their clinical implications?
Dr. Jiangao Fan: At this year’s AASLD, our team’s foundational research on the pathogenesis of metabolic dysfunction-associated steatohepatitis was recognized as an “Outstanding Poster” (No. 1044). This study focused on the role of hepatic macrophages (Kupffer cells) in the development of steatohepatitis and fibrosis and explored their potential as therapeutic targets.
Additionally, we presented research on the genetic-metabolic liver disease Wilson disease (WD) and its association with fatty liver (No. 4467). Using an ATP7B gene knockout model and in vitro experiments, we investigated how hepatic copper accumulation affects lipid metabolism and the potential impact of high-fat, high-cholesterol diets on copper metabolism. Our findings revealed critical regulatory targets in lipid metabolism during WD progression. We also demonstrated the efficacy of gene therapy using an AAV8 vector encoding ATP7B in alleviating liver damage caused by WD. Furthermore, our studies suggest that fatty liver in WD is more closely linked to host metabolic dysfunction, with copper playing a contributory but not decisive role.
Reflections on AASLD Participation
Hepatology Digest: Could you share your thoughts and takeaways from attending the AASLD annual meeting?
Dr. Jiangao Fan: Attending academic conferences fosters meaningful exchanges and creates valuable opportunities for interdisciplinary collaboration. Despite the physical demands of participation, the wealth of knowledge and insights gained is truly invaluable. International in-person meetings, like AASLD, open windows to a broader academic world, enhancing our perspectives and facilitating global collaborations.
These events also break the monotony of daily clinical and research routines, offering a balanced pace of work and relaxation. Such experiences not only rejuvenate the mind but also inspire fresh ideas and renewed enthusiasm for advancing our work upon returning to our respective institutions.
