Surfing the NASH Tsunami has explored issues of NASH cirrhosis since our first several episodes in 2020. This episode integrates three different issues to consider the most important challenges in treating patients with NASH cirrhosis today, with one panelist having expertise in at least one perspective. Jörn Schattenberg was an author of the #ILC2022 late-breaker presentation discussing semaglutide in NASH cirrhosis. Antaros Medical co-founder and Chief Scientific Officer Lars Johannson has discussed and published on different ways to evaluate the impact of medications on cirrhosis. Louise Campbell’s career in nursing and subsequent work at Tawazun Health has focused on providing patients with the information and support they need to improve their own conditions.
What Do We Know That Can Help NASH Cirrhosis Patients Today?
Roger Green starts the dialog by recounting the cirrhosis discussions over the life of the podcast. He recalls earlier discussions with Manal Abdelmalek about using older medicines (statins, metformin) that might benefit patients, particularly since a significant number even of compensated cirrhotics will decline relatively quickly. Jörn Schattenberg picks up this line of discussion, then goes on the describe the semaglutide late-breaker at ILC2022. In describing the study, Jörn notes that while it failed to meet the end point of fibrosis regression in 48 weeks, it improved a range of metabolic markers while demonstrating a strong safety profile in this population.
In the next stage of discussion, Jörn notes the importance of early (okay, earlier) diagnosis in these patients and notes that ELF is indicated in the US and EU to confirm a diagnosis of cirrhosis.
Lars Johansson joins the conversation to ask Jörn whether he believes the challenge in the semaglutide study is that 48 weeks is too short a time to expect fibrotic regression in cirrhotic patients. After Jörn concurs, Lars adds several encouraging comments about effects seen with sema in this population: 20-30$ reduction in spleen volume and early signs of portal pressure that suggest to Lars we are “doing something good” even if the drug does not regress fibrosis within the study period.
This topic leads to a conversation about some of the measures that Lars focuses on to determine how well (or poorly) the liver and overall metabolic system are working in the target patient population. Lars notes that when evaluating other diseases (heart, kidney), we look directly at organ function whereas with liver we look at biopsies.
At this point, Roger asks the group where they believe the next breakthrough in cirrhosis therapy is likely to occur. Louise points to the need to improve patient communications, given how many patients do not learn they have ANY liver disease until their initial cirrhosis diagnoses. When patients have data and an understanding of their condition, she notes, they are “urgent” to support their own health. Jorn states that a key to resolving this issue is to create simple, automated measures that will allow the patient’s risk status to appear on an electronic medical record or other calculation. Lars foresees a major breakthrough when we can study imaging results along with circulating biomarkers in order to identify a single biomarker (or a small group of them) that can predict advanced disease.
Louise returns to the point that without improved communications, we will fail to keep patients engaged in their own therapy, which will lead to more failure, illness and severe consequences. This leads Roger to describe the next stage as a “pincer movement,” with high-tech diagnostics and new drugs on one end and better human systems engineering and electronic communication on the other.
As the conversation starts to wind down, Roger asks Lars what he sees as the areas where we will translate what he is learning into improved diagnostics. Lars and Jörn agree that the best strategy is a first stage of inexpensive screening to rule out patients without disease, and then probably a CT-based evaluation to appreciate the status of the liver and impact on related organ systems.
As the conversation wraps up, Roger asks where each panelist sees the greatest potential for growth in the next 1-2 year. Louise and Jörn focus on improved patient communication and simple screening, while Lars talks with excitement about starting to garner large amounts of data from some of the large, long-term outcome studies that Antaros is involved in. Roger agrees with both points of view and highlights drug approvals’ impact in bringing additional investment into the Fatty Liver system for drug development, patient and provider education, and even support of diagnostics.