# Efficacy of ursodeoxycholic acid in metabolic dysfunction-associated steatotic liver disease: an umbrella review of meta-analyses on liver enzymes

**Authors:** Alsu R. Khurmatullina, Dmitrii N. Andreev, Igor V. Maev, Andrey V. Zaborovsky, Yury A. Kucheryavyy, Petr A. Beliy, Philipp S. Sokolov

PMC · DOI: 10.3389/fmed.2026.1771830 · Frontiers in Medicine · 2026-02-13

## TL;DR

This study reviews multiple analyses to assess how well ursodeoxycholic acid improves liver health in people with metabolic-related fatty liver disease.

## Contribution

The study provides a comprehensive umbrella review of meta-analyses on UDCA's effects on liver enzymes in MASLD.

## Key findings

- UDCA significantly reduces ALT, AST, GGT, and ALP levels in MASLD patients.
- Longer treatment duration is associated with greater ALT reduction.
- UDCA shows consistent hepatoprotective and cholestasis-modifying effects.

## Abstract

This 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.

Following 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.

Five 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).

UDCA demonstrates consistent hepatoprotective and cholestasis-modifying effects in MASLD. Longer treatment duration may enhance biochemical responses.

CRD420251250211.

## Linked entities

- **Chemicals:** ursodeoxycholic acid (PubChem CID 31401)
- **Diseases:** metabolic dysfunction–associated steatotic liver disease (MONDO:0013209), MASLD (MONDO:0013209)

## Full-text entities

- **Genes:** PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, NR1H4 (nuclear receptor subfamily 1 group H member 4) [NCBI Gene 9971] {aka BAR, FXR, HRR-1, HRR1, PFIC5, RIP14}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, GGTLC4P (gamma-glutamyltransferase light chain 4 pseudogene) [NCBI Gene 729838] {aka GGT}, GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}, ATHS (atherosclerosis susceptibility (lipoprotein associated)) [NCBI Gene 470] {aka ALP}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}
- **Diseases:** type 2 diabetes (MESH:D003924), liver conditions (MESH:D017093), hepatocellular injury (MESH:D056486), hepatocellular carcinoma (MESH:D006528), atherogenesis (MESH:D050197), cholestasis (MESH:D002779), cardiovascular disease (MESH:D002318), hemorrhagic shock (MESH:D012771), insulin resistance (MESH:D007333), obesity (MESH:D009765), Fatty Liver (MESH:D005234), metabolic dysfunction (MESH:D008659), hepatocyte damage (MESH:D020263), cirrhosis (MESH:D005355), injury (MESH:D014947), MASLD (MESH:D008107), hepatic inflammation (MESH:D007249), cirrhotic (MESH:D000094724), intrahepatic cholestasis (MESH:D002780), NAFLD (MESH:D065626)
- **Chemicals:** UDCA (MESH:D014580), lipid (MESH:D008055), glucose (MESH:D005947), bile acid (MESH:D001647), Ursodeoxycholic Acid"[MeSH (-), hydrogen peroxide (MESH:D006861), fatty acid (MESH:D005227), bilirubin (MESH:D001663)
- **Species:** gut metagenome (species) [taxon 749906], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12945775/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945775/full.md

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Source: https://tomesphere.com/paper/PMC12945775