Surfing the MASH Tsunami continues its 2023 wrap-up conversations with hepatology researcher and key opinion leader Naim Alkhouri of the Arizona Liver Health Institute, along with co-hosts Louise Campbell and Roger Green. The conversation focuses on viewing the year’s major events in drug development, non-invasive tests (NITs) and clinical care pathways.
This conversation starts with Roger asking Naim his reaction to 2023. Naim starts by mentioning his disappointment that OCA did not get approved, but shares his vision that the data presentation did not support approval and his hope and believe that resmetirom will fare better. From there, he shifts quickly to discuss being “a little bit disappointed” at the implementation of the AACE and AGA guidelines. In practical terms, he has not seen a single referral from primary care practices (PCP) for elevated FIB-4. He notes that this will require better education of PCPs, but also expresses concern that the guidelines might not be practical for them. In the effort “not to miss a single patient,” he believes, authors have created a system with too many patients screened, found negative and sen back to the PCP. Instead, he suggests, guidelines should have a more realistic goal (reduced unidentified patients from 95% to 80%), and rely on higher FIB-4 cutoffs until PCPs have integrated the concept of MASH screening into their practices. Wrapping up his view of 2023, he describes it as a “good year,” although unfortunately one in which drug approval and increased pathway use did not occur.
Roger suggests that the same phenomenon — worrying more about making things perfect than making them implementable — applied to the original rollout of the new nomenclature as well as pathways, and goes on to discuss what he sees as the behavioral psychology implications of the pathway guidelines. Naim responds with two suggestions: raise the minimum PIB-4 score at which patients are referred to 2.67 and, in the US, reflex to an ELF test before sending patients to specialists. Louise notes that ELF is not as readily available in the UK as Americans might assume. Roger adds that it might be of value to educate PCPs on the value of FIB-4 as predictive of MACE and other forms of mortality.
Roger asks Naim to describe the “biggest wins” of 2023. Naim starts by citing specific advances in NITs, specifically mentioning NIS-2+ and MASEF (discussed in S4 E39). In terms of medications, he discussed the double- and triple-incretin agonists and their ability to support patients in defatting their livers and notes that, of course, resmetirom’s positive Phase 3 results are the biggest story. His third item is that expansion of multi-specialty meetings that educate other specialties on SLD, why it matters and what roles the other specialties can play in diagnosing and managing MASH patients.
Roger’s next question is about disappointments. Naim wishes FDA had moved further, faster in alternate drug approval pathways and metrics, but sees progress in terms of their openness to exploring NITs and, more exciting, their recently stated willingness to grant full approvals in cirrhosis based on histology. Roger asks how AI fits into the emerging picture. Naim states that AI analyses can teach a great deal about the disease, but is not practical for patient treatment.
The last question: his most optimistic picture for 2024 starts with resmetirom approval, goes on to mention several exciting potential drug development results, and then discusses creating MASL Centers of Excellence relying on robust NITs for diagnosis and management.