A new natural history study of patients with metabolic dysfunction–associated steatohepatitis shows a six-year mortality rate of 10% in patients with compensated cirrhosis.

The new data supplement what is known from clinical trials, which may not be representative of the broader population, according to Sidney Barritt IV, MD, MPH, who presented the study at The Liver Meeting 2024 (abstract 2357).

“The purpose of this study is to observe their natural history, … disease course, [and] predictors of progression of disease and, ultimately, to be a source of phase four post-marketing surveillance once medications are available for the treatment of this disorder,” said Dr. Barritt, a professor of medicine at the University of North Carolina at Chapel Hill.

The researchers analyzed data on 1,949 patients (1,084 with non-cirrhotic MASH, 495 with compensated cirrhosis and 370 with decompensated cirrhosis) enrolled in the TARGET-NASH database between August 2016 and January 2024. About one-third of the patients in the study had been biopsied, but most diagnoses were made based on clinical criteria, “just like they are in routine clinical practice,” Dr. Barritt said.

Compared with non-cirrhotic MASH patients, those with compensated cirrhosis had increased rates of all-cause mortality (hazard ratio [HR], 13.62; 95% CI, 6.13-30.29) and progression to decompensated cirrhosis (HR, 52.24; 95% CI, 24.28-112.40) over six years of follow-up. The risk for all-cause mortality was about 10% in patients with compensated cirrhosis and 30% in those with decompensated cirrhosis over that period.

Progression from MASH to compensated cirrhosis was 1.39 per 100 person-years, and from compensated to decompensated cirrhosis was 3.53 per 100 person-years. Among individuals with MASH, 6% progressed to compensated cirrhosis in six years, and 14% with compensated cirrhosis had a decompensation event.

The findings revealed some characteristics of MASH patients. “Our population of patients with MASH progressed relatively slowly to cirrhosis, granted [the study included] all fibrosis stages of MASH,” Dr. Barritt told Gastroenterology & Endoscopy News.

In contrast, he added, “the progression of patients with decompensated cirrhosis happened relatively quickly.” By 12 months, 10% of the cohort with decompensated cirrhosis had died, and by 36 months, approximately 20% of that group had died. “That’s relatively rapid progression and a large disease burden, and frequently patients with decompensated cirrhosis are not part of clinical trials, so this is a way to follow these patients over time,” Dr. Barritt said.

The findings “speak to that critical unmet need for a non-transplant intervention to try to help these people, especially those with compensated cirrhosis.”

—Jim Kling

The study was funded by Merck. Dr. Barritt reported financial relationships with Boehringer Ingelheim, Madrigal, Merck, Mirum and Target RWE.