Type 2 Diabetes and Obesity are The Main Metabolic Risk Factors for The Development of Cirrhosis in People with Metabolic Dysfunction Associated Steatohepatitis.

Challenge

T2D is widely recognized as a risk factor for MASH progression, but real-world prospective data establishing T2D as an independent predictor of cirrhosis development—controlling for baseline fibrosis and other metabolic factors—were lacking, limiting the strength of T2D as an enrollment enrichment criterion.

Solution

The TARGET-NASH cohort was used to analyze progression from non-cirrhotic MASH to compensated cirrhosis in patients with and without T2D, using multivariable hazard models adjusted for age, sex, and fibrosis risk to isolate the independent contribution of T2D to cirrhosis risk.

Impact

Establishing T2D as an independent predictor of MASH progression to cirrhosis in a prospective real-world cohort provides the evidence base for T2D-based enrichment in MASH trials and supports regulatory arguments for T2D subgroup analyses in MASLD development programs.