Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial
Open accessAbstract
No effective medical therapy is available for all patients with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) has been suggested to be of benefit based on open label clinical studies. We randomized 166 patients with liver biopsy-proven NASH to receive between 13 and 15 mg/kg/d of UDCA or placebo for 2 years. End points included changes in liver test results and liver histology at 2 years of therapy. The treatment groups were comparable at entry with regard to age, gender, risk factors for NASH, serum liver biochemistries, and baseline liver histology. A total of 126 patients completed 2 years of therapy. Pre- and posttreatment liver biopsies were available in 107 patients for review at the end of the study. UDCA was well tolerated and body weight was stable during the study duration. Serum liver biochemistries were stable or improved in both the UDCA and placebo-treated groups. Changes in the degree of steatosis, necroinflammation, or fibrosis that occurred with therapy were not significantly different between the UDCA and placebo groups. In conclusion, 2 years of therapy with UDCA at a dose of 13 to 15 mg/kg/d, although safe and well tolerated, is not better than placebo for patients with NASH.
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Despite limitations and methodological differences, there is a strong indication of biochemical efficacy (ALT reduction) and a good safety profile for UDCA, but no proof of histological efficacy.
“Despite several limitations and methodological differences, there is a strong indication of biochemical effi cacy (ALT reduction) and a good safety pro fi le, but no proof of histological ef fi cacy.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [373]
The Discussion says UDCA did not improve liver biochemistries compared with placebo; ALT fell in both groups, so the trial contradicts the claimed strong indication of biochemical efficacy. The Histological Response section supports the absence of demonstrated histological efficacy, and the Adverse Events section reports similar overall adverse-event rates between groups. Page numbers were not available in our copy. (LLM, conf=0.90)
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Experimental — accuracy not yet measuredThere are three larger, placebo-controlled trials of UDCA in MASH differing in dose, and only two report histological endpoints.
“There are three larger, placebo-controlled trials of UDCA in MASH differing in the dose of UDCA used 373 -375 and only two of them report histological endpoints.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [373]
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- Authors
- Lindor, K. D., Kowdley, K. V., Heathcote, J. E., Harrison, E. M., Jorgensen, R., Angulo, P., Lymp, J. F., Burgart, L., & Colin, P.
- Affiliations
- Mayo Clinic (US)
- University of Washington (US)
- Toronto Western Hospital (CA)
- Mayo Clinic in Arizona (US)
- Corresponding author
- Lindor, Keith D.
- Venue
- Hepatology
- Published
- 2004-03
- Volume
- 39
- Issue
- 3
- Pages
- 770-778
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2139112405
- Cited by
- 727
- References
- 26
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 18 · 2023: 18 · 2022: 19 · 2021: 26 · 2020: 21 · 2019: 27 · 2018: 26 · 2017: 24 · 2016: 33 · 2015: 45 · 2014: 30 · 2013: 40 · 2012: 44
- FWCI
- 35.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Baylor University
- Baylor University Medical Center
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- ursodeoxycholic acid, nonalcoholic steatohepatitis, NASH treatment, liver histopathology, steatosis, necroinflammation, liver fibrosis, liver enzymes, placebo comparison, drug safety and tolerability
- MeSH terms
- Alanine Transaminase, Aspartate Aminotransferases, Cholagogues and Choleretics, Double-Blind Method, Fatty Liver, Fibrosis, Humans, Liver, Necrosis, Ursodeoxycholic Acid, Disease Progression
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