Last month, roughly 5,000 liver community stakeholders gathered in London for the 2022 International Liver Congress (#ILC2022.) On Thursday afternoon, Scott Friedman chaired an abstract session discussing advances in the basic science of researching and understanding mechanisms surrounding fibrosis and stellate cells. Later, he described it as “one of the most exciting groups of presentations I’ve seen in many years.” The conversation starts with Roger Green asking the panel how to pay this research off in terms of commercial benefit. Most of the conversation consists of their answers.
Scott Friedman answers Roger’s question first. He notes that these advanced techniques will allow us to focus on not only the right type of cell but the right subtype(s). Hitting the right target dead-on will improve the efficacy of drugs and the accuracy of diagnostics. Also important (perhaps more so): we can avoid what Scott calls “off-target effects”, which commercial executives might think of as safety, tolerability and side effect issues.
Commercial Benefit From the New Liver Science
Consistent with other themes NASH Tsunami visits regularly, Jörn notes that the future of therapy is likely to be individualized, multi-element and probably multi-phase. The more this basic research can teach us about the disease process stages and how they vary by patient, the better job drug developers can do in developing medicines that resolve specific patients’ needs.
Scott notes that if we can hypothesize which patients will respond best to a specific intervention, we can streamline clinical trials, possibly reduce sample sizes, separate respondents from non-responders better and/or shorten trial durations. All these possible outcomes stem from the increasingly demonstrable reality that NAFLD or NASH is actually a set of related diseases rather than a single, uniform disease process.
As the session begins to wind down, Roger invites Scott to discuss any other topics that emerged from the abstract session. Scott mentions the last paper in the session, where researchers from Heidelberg explored a specific receptor whose acronym is RAGE (Receptor for Advanced Glycation End-products). RAGE drives what Scott terms “a very important response,” seen both in NASH and cholestatic disease, in which bile duct proliferate. This is called a ductular reaction. As Scott notes, both the cause of this reaction and its relationship to fibrosis have been “a bit hazy.” Now, this group has identified some players that might be involved in this process…and identified them in such a way that therapeutics are being developed against RAGE. This will benefit NASH and, even more clearly, cholestatic diseases.
As a last question before wrapping up, Roger asks the rest of the panel if they have comments about the meeting aside from this session. Neil points to the optimism and energy caused not only by the new methods but also the sharing of knowledge AND larger data sets, all of which can lead to molecular pathology-based approaches that will help us define the multiple diseases in the NAFLD galaxy better. Jörn goes almost to the other extreme, commenting on presentations demonstrating the value of FIB-4 as a first-line screening tool and others challenging FIB-4 the same way. To Jörn, this identifies the need for a better first-line screening test, which the kinds of research covered in this session might produce. Roger closes the conversation by noting that the two outstanding benefits of FIB-4 are its low cost and wide availability, which suggests the next steps we are more likely to see is a staged approach to diagnosis and screening.
