In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, Scott Friedman joins to discuss his perspective on what has been an eye-opening year for liver science.
In the Season 3 NAFLD Year-in-Review conversations series, Surfers Jörn Schattenberg, Louise Campbell and Roger Green embark on a string of interviews with a handful of Key Opinion Leaders who made headlines and advances in Fatty Liver disease in 2022. In this exclusive segment, Scott Friedman joins to discuss his perspective on what has been an eye-opening year for liver science.
Scott prefaces this session with the idea that in the absence of an approved drug, the field has responded with an urgency to develop improved pathways and targets. This urgency is coupled with progressive efforts to modify and improve clinical trials and endpoints, and noninvasive markers to make those trials more streamlined and accessible. From here he introduces illuminating findings on genetic variants associated with protection from Fatty Liver disease. An attention-grabbing conclusion: rare germline mutations in the CIDEB gene conferred substantial protection from liver disease. Scott states the implications are twofold. This summons recognition of the power of genetics in uncovering new pathways. This also highlights the complexities of a disease featuring genetic variants that may variably contribute to the likelihood that a patient with obesity develops NASH. He suggests that broadly, the challenge in NASH is sifting through an enormous palette of drivers – be it genetic, derived from the microbiome, or attributable to diabetes and the consequences of metabolic syndrome. All of which influence how we decide to establish and prioritize strategies for the discovery of new therapeutic targets. Reinforcing his recent comment on the podcast that gene therapy has effectively arrived, he notes the speed by which genetic information can translate into real therapies.
Continuing on the theme of scientific advancements, Scott points to papers emerging from the Columbia University lab of Robert Schwabe. The aim of the Schwabe lab is to understand the regulation of wound healing responses to chronic liver injury with a specific focus on how the activation of hepatic stellate cells (HSCs) promotes liver fibrosis and liver carcinogenesis. Scott raises a spate of compelling questions in response to Schwabe’s interrogation and subsequent findings on functions of HSCs, the main source of liver fibroblasts, during hepatocarcinogenesis. He accredits the feasibility of these studies back to the emerging availability of single cell sequencing technologies. Once again, Scott reveals his acceptance that the “devil is in the details,” alluding to the back-and-forth switching capacity of particular cellular functions. By identifying the transcription factor that drives this switching to a protective role, Scott suggests there is potential to enhance the expression of that transcription factor using gene therapy. Whether we can realistically expect to change the behavior of cells in the setting of an injured liver through the manipulation of gene expression is something to look forward to. “The best is yet to come.”
The group breaks into a brief discussion around the stepwise commercial progression and eventual success of Hepatitis C treatment. As the interview winds down, Scott returns to one last paper of interest stemming from his own laboratory and set to be published in the imminent future. The focus of the paper postulates stage-specific therapies as NASH develops. While admittedly “a long way off” from a clinical setting, this project framework injects Scott with invigoration to address possibly the largest unmet need of patients who have or are approaching cirrhosis. Surf on to his upcoming NASH-TAG talk for a more explicit demonstration of this unfolding story.
