GLP-1 RAs improve liver function in most patients. SYNERGY-NASH and ESSENCE position the class as emerging MASH therapy.
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Baseline liver labs
ALT, AST, alkaline phosphatase, bilirubin baseline before starting. FIB-4 score (calculated from AST, ALT, platelets, age) classifies fibrosis risk.
Most patients improve
Significant weight loss + direct hepatic effects of GLP-1 RAs typically produce: ALT/AST decline, decreased steatosis on imaging, fibrosis improvement over years.
When labs worsen
Uncommon but concerning. ALT/AST >3× ULN: workup including imaging and hepatology referral. Don't assume GLP-1 is causal — alcohol, medications, viral hepatitis, autoimmune causes still need consideration.
MASH-specific consideration
SYNERGY-NASH (tirzepatide) showed 44–62% MASH resolution at 52 weeks; ESSENCE (semaglutide) interim May 2026 showed ~62%. Plausible 2027 FDA MASH indication. For biopsy-confirmed MASH F2-F3, hepatology coordination is essential.