Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH
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Summary: Background: Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. There is a major need to understand the efficacy of different pharmacological agents for the treatment of NASH. Aim: To assess the relative rank‐order of different pharmacological interventions in fibrosis improvement and NASH resolution. Methods: A comprehensive search of several databases was conducted by an experienced librarian. We included randomised controlled‐trials (RCTs) comparing pharmacological interventions in patients with biopsy‐proven NASH. The primary outcome was ≥1 stage improvement in fibrosis. The secondary outcome was NASH resolution. Results: A total of 26 RCTs with 23 interventions met the eligibility criteria. Lanifibranor and obeticholic acid had the highest probability of being ranked the most effective intervention for achieving ≥1 stage of fibrosis improvement (SUCRA 0.78) and (SUCRA 0.77), respectively. For NASH resolution, semaglutide, liraglutide and vitamin E plus pioglitazone had the highest probability of being ranked the most effective intervention for achieving NASH resolution (SUCRA 0.89), (SUCRA 0.84) and (SUCRA 0.83), respectively. Lanifibranor, obeticholic acid, pioglitazone and vitamin E were significantly better than placebo in achieving ≥1 stage of fibrosis improvement. Conversely, semaglutide, liraglutide, vitamine E plus pioglitazone, pioglitazone, lanifibranor and obeticholic acid were significantly better than placebo in achieving NASH resolution. Conclusion: These data provide relative rank‐order efficacy of various NASH therapies in terms of their improvements in liver fibrosis and NASH resolution. Therapies that have been shown to improve NASH resolution may be combined with therapies that have an antifibrotic effect to further boost treatment response rate in future.
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Gut-derived hormones such as GLP-1 receptor agonists, dual agonists, and the FGF-19 mimetic aldafermin are already in clinical use or advanced development for metabolic diseases.
“Gut-derived hormones are already in clinical use for metabolic diseases (e.g. GLP-1 receptor agonists, such as semaglutide or liraglutide, GLP-1/GIP [glucose-dependent insulinotropic polypeptide] dual agonists, such as tirzepatide) or in advanced clinical development (e.g, GLP-1/glucagon dual agonists, such as cotadutide, or the FGF-19 mimetic aldafermin).11,45”
From An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH (2023) · cites this paper as [45]
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- Authors
- Majzoub, A. M., Nayfeh, T., Barnard, A., Munaganuru, N., Dave, S., Singh, S., Murad, M. H., & Loomba, R.
- Affiliations
- Conemaugh Memorial Medical Center (US)
- Mayo Clinic (US)
- University of California San Diego (US)
- Corresponding author
- Loomba, Rohit
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2021-08-25
- Volume
- 54
- Issue
- 7
- Pages
- 880-889
- ISSN
- 0269-2813 (ISSN-L)
- 1365-2036
- PMC
- PMC8711247
- OpenAlex
- W3193811807
- Cited by
- 92
- References
- 52
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 18 · 2023: 20 · 2022: 24 · 2021: 2
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alimentary Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Environmental Health Sciences (5P42ES010337)
- National Center for Advancing Translational Sciences (5UL1TR001442)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK061734, R01DK106419, P30DK120515, R01DK121378, R01DK124318)
- National Heart, Lung, and Blood Institute (P01HL147835)
- National Institute on Alcohol Abuse and Alcoholism (U01AA029019)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- nonalcoholic steatohepatitis, NASH resolution, lanifibranor, obeticholic acid, semaglutide, liraglutide, pioglitazone, vitamin E, antifibrotic agents
- MeSH terms
- Pioglitazone, Biopsy, Humans, Liver Cirrhosis, Vitamin E, Non-alcoholic Fatty Liver Disease
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