An article in the New England Journal of Medicine discusses the drug tirzepatide in the treatment of metabolic dysfunction associated with steatohepatitis (MASH) with liver fibrosis.[1][2] Tirzepatid is being evaluated in a clinical program where it demonstrates a positive hepatic effect beyond weight loss, including improvements in insulin sensitivity, hepatic metabolism, and inflammation.[2] Liver fibrosis is a key predictor of hepatic, cardiovascular and tumor complications of MASH and requires non-invasive diagnostics to assess its stage.[1][2][3] MASH with clinically significant fibrosis (at-risk MASH) is the main indication for treatment.[1] In comparison, resmetirom was the first drug to receive conditional FDA approval for non-cirrhotic MASH with intermediate to advanced fibrosis.[2][3] New therapies, including tirzepatide, target hepatic metabolism, inflammation, and fibrosis in clinical trials.[2] Treatment combines regimen therapy with pharmacological interventions to reverse disease progression.[1]