S3-E53.2 - Serum Metabolomics, Gene Therapy and the Waning Future of Biopsy

Recorded onsite in Washington DC, Scott Friedman, Jörn Schattenberg, Rachel Zayas and Roger Green discuss takeaways from the first three days at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The group encapsulates the dynamic, vibrant energy of returning to this momentous event which welcomed back over 7,000 in-person attendees.<br/><br/>Jörn starts this conversation by introducing a paper titled, The Effect of a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist, Cotadutide, on Serum Metabolome in Biopsy-Proven Non-Cirrhotic NASH with Fibrosis. He describes Cotadutide followed by the study design that added metabolomic analyses to more standard liver NITs. Serum metabolomics is an emerging non-invasive tool that may identify novel biomarkers for disease stratification and treatment efficacy. Jörn advocates for drug developers to consider adding metabolomic assessments to clinical trials.<br/><br/>Scott shifts focus to note that while our community is liver-centric, Fatty Liver disease is complex and therapies can affect other organs. He wonders how the benefit of these therapies may accrue from effects outside the liver, particularly muscle and adipose tissues. Rachel cautions that emerging gene therapies ought to evaluate the potential off target effects that might be introduced by silencing a gene expression in the liver. In agreement, Scott aptly responds that gene therapy has arrived. In an example from the COVID-19 pandemic, he highlights the development of finely tuned lipid nanoparticle carriers. Roger suggests there is considerable value in the approach of finding a solution, fixing the problem and then figuring out what happened.<br/><br/>The group continues on to discuss an abstract presented by Amrik Shah titled, Histologic Endpoints in NASH Clinical Trials: The Emperor Has No Clothes. This paper evaluated the effects of the imprecision of histologic reading and the consequent effects in therapeutic trials. Scott asserts the need for digital pathologies to enter the mainstream as endpoints in clinical trials. This sparks comments around Arun Sanyal’s redefinition of the REGENERATE data in Late Breaking Oral Abstract, Session 2. As the session winds down, Scott notes the licensing board in the US is no longer requiring liver biopsy as part of gastroenterology or liver training. “People are voting with their feet whether someone wants a claim to biopsy or not. It's only a matter of a generation.”