Given the vast amount of information and insight from The Liver Meeting, this episode sought to identify and explore a few key highlights. Even so, there is more in this episode than a brief summary can capture. The panel (Jörn Schattenberg, William Alazawi, Naim Alkhouri, Laurent Castera, Ken Cusi, Wayne Eskridge and Roger Green) address several topics from the program:
Wayne presents information from a survey Fatty Liver Foundation conducted with NAFLD patients. The study reported that very few patients received adequate information at time of diagnosis, and one in three do not even receive a specialist referral. This sparks general discussion on how to drive stronger provider-to-patient communication. The group goes on to consider the value of testing and standardized score computation in medical records, which can improve screening and provider education to patients. One challenge here: AST, which is a key test in its own right and as part of FIB-4, is part of the standard test battery only in the US.
In the minds of the panelists, provider information and education is and will remain a major challenge. Laurent notes that in France, providers associated cirrhosis with alcohol consumption, but not diet. Ken suggests that getting primary care providers to associate cirrhosis with fatty liver is a key step to improving screening and education.
Naim points to the open-label resmetirom study with cirrhotic patients as providing “very promising results” in a range of non-invasive tests. He shares his enthusiasm that so many of the emerging guidelines rely on the same cut points in NITs. He goes on to discuss a study in which he and others evaluated the impact of using these guidelines (FIB-4 cut points, VCTE as second step, T2DM and metabolic patients as targets).
Naim notes that if applied appropriately, the paper estimated only 8% of the US population would have any need to be treated by a hepatologist, and perhaps only 4-5 million would require intervention with expensive medications.
Laurent shares a prospective screening study on patients with diabetes located in primary care settings or diabetes clinics based in the US. Using NITs to screen for NASH and MRE to screen for advanced disease, they identified 65% with NAFLD, 14% with advanced fibrosis and 5% with cirrhosis. When 164 of these patients moved into biopsy, they identified 61% with NAFLD, 30% advanced NASH and 9% cirrhosis. Laurent contrasts these results to a similar study conducted in a French diabetes clinic-treated cohort. The panelists explore the implications of both studies in terms of how should screening be conducted today. Jörn notes that we must consider the incentive for a physician to screen or enroll a patient.
Ken discusses advances in the use of PPARs, noting first the ongoing work with the pan-PPAR lanifibranor followed by Poxel’s work with PXL-065. The latter is a deuterium-stabilized form of pioglitazone that generates greater activity of the r-enantiomer and less of the s-enantiomer. These are linked to mitochondrial benefit versus weight gain, respectively.
Naim calls attention to the failing performance of NITs in pediatric NASH. Roger recalls the SPLENDOR Study (discussed on Season 2, Episode 60) and what it reveals of the ability for bariatric surgery-driven 20% weight loss to regress fibrosis in non-cirrhotic patients. Panelists then briefly discuss Scott Friedman’s observation from last week’s coverage about the impact of environmental factors on the microbiome and how that might affect these metabolic issues.
Roger closes by asking the group for one thing, besides a drug approval, that will change how we think about or treat this disease in the next year. Surf on to discover their predictions.
