Abstract
CLINICAL, BIOLOGICAL AND IMAGING PREDICTORS OF AT-RISK METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (MASH): COMBINED DATA FROM MULTIPLE THERAPEUTIC TRIALS INCLUDING MORE THAN 6,000 PATIENTS (IN COLLABORATION WITH NAIL-NIT CONSORTIUM)
Background:
The identification of at-risk metabolic dysfunction-associated steatohepatitis (MASH) patients remains a main challenge in both clinical practice and clinical trial settings. Several non-invasive biomarkers have been developed to identify those at-risk MASH patients who would benefit from pharmacological therapy. We aimed to describe the main predictors of at-risk MASH across multiple therapeutic clinical trials.
Methods:
We combined screening data from 7 MASH non-cirrhotic phase 2 trials. Predictors of at risk-MASH were examined using logistic regression and excluding patients with cirrhosis
Results:
Out of the 6,558 patients, 2,173 with centrally assessed liver biopsy were included. Among them, 912 (42%) met the histopathological criteria for at-risk MASH. The predictors of at-risk MASH are shown in Table 1. The proportion of at risk-MASH patients was 12%, 26%, 42% and 61% in patients with AST <20, AST 20-30, AST 30-40, and AST ≥ 40, respectively. This rises to 54% in patients with AST ≥ 30 versus 23% in patients with AST <30. In patients with FAST<0.35, FAST 0.35-0.67, and FAST ≥ 0.67, 34%, 58%, and 74% were “at-risk MASH”, respectively. This rises to 69% for patients with FAST ≥ 0.5 versus 40% in patients with FAST <0.5. When focusing on Fib-4 categories (<1.3, 1.3-2.67, ≥ 2.67), the at-risk MASH population represented 31%, 56%, and 75% of the patients, respectively. The proportion of at-risk MASH patients was 35% in patients with HbA1c <6.5% compared to 53% in patients with HbA1c ≥ 6.5%. In the population with FAST ≥ 0.50, 76% of patients with HbA1c ≥ 6.5% were “at-risk MASH” compared to 64% with HbA1c <6.5%. Similarly, in the subgroup with FAST ≥ 0.67, patients with HbA1c ≥ 6.5% had a higher probability of at-risk MASH (78%) compared to those with HbA1c <6.5% (70%).
Conclusion:
Simple non-invasive biomarkers can help stratify at-risk MASH patients. We recommend using the FAST-score as a simple tool to target at-risk MASH patients with a cutoff point of 0.5 for patients with HbA1c ≥ 6.5% and 0.67 for patients with HbA1c <6.5%.