Supplementary file 2_Efficacy of ursodeoxycholic acid in metabolic dysfunction-associated steatotic liver disease: an umbrella review of meta-analyses on liver enzymes.docx

ObjectiveThis umbrella review aimed to systematically synthesize and evaluate evidence from published meta-analyses regarding the efficacy of ursodeoxycholic acid in metabolic dysfunction–associated steatotic liver disease, focusing on its impact on liver-specific biochemical markers.
MethodsFollowing Joanna Briggs Institute methodology and registered in PROSPERO (ID: CRD420251250211), a comprehensive search of MEDLINE, EMBASE, Cochrane Library, and Scopus (1985–2025) identified systematic reviews and meta-analyses evaluating UDCA therapy in MASLD. Methodological quality was appraised using AMSTAR-2, ROBIS, and GRADE frameworks. Data on hepatic biomarkers were extracted and synthesized using fixed- or random-effects models depending on heterogeneity (I2 statistic). Overlap among primary studies was assessed using the GROOVE tool, and meta-regression explored the influence of treatment duration on ALT dynamics.
ResultsFive meta-analyses (33 primary studies; 5,015 participants) were eligible. UDCA demonstrated consistent and statistically significant improvements in key markers of hepatocellular injury, including ALT (SMD = −0.36; 95% CI: −0.69 to −0.03) and AST (SMD = −0.16; 95% CI: −0.22 to −0.10), as well as cholestatic markers such as GGT (SMD = −0.40; 95% CI: −0.63 to −0.18) and ALP (SMD = −0.23; 95% CI: −0.31 to −0.14), total bilirubin decreased modestly (SMD = −0.08; 95% CI: −0.15 to −0.01), while albumin level remained unchanged. Meta-regression showed that longer treatment duration was significantly associated with greater ALT reduction (−0.04 SMD per 6 months; p = 0.034).
ConclusionUDCA demonstrates consistent hepatoprotective and cholestasis-modifying effects in MASLD. Longer treatment duration may enhance biochemical responses.
Systematic review registrationCRD420251250211.