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Observational Study
. 2025 Mar;31(3):988-995.
doi: 10.1038/s41591-024-03480-y. Epub 2025 Jan 27.

Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis

Ali Aminian  1 , Abdullah Aljabri  1 , Sarah Wang  1 , James Bena  2 , Daniela S Allende  3 , Hana Rosen  1 , Eileen Arnold  1 , Rickesha Wilson  1 , Alex Milinovich  2 , Rohit Loomba  4 , Arun J Sanyal  5 , Naim Alkhouri  6 , Jamile Wakim-Fleming  7 , Sobia N Laique  7 , Srinivasan Dasarathy  7 , Arthur J McCullough  7 , Steven E Nissen  8
Affiliations
Observational Study

Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis

Ali Aminian et al. Nat Med. 2025 Mar.

Abstract

No therapy has been shown to reduce the risk of major adverse liver outcomes (MALO) in patients with cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) observational study compared the effects of metabolic surgery and nonsurgical treatment in patients with obesity and compensated histologically proven MASH-related cirrhosis. Using a doubly robust estimation methodology to balance key baseline characteristics between groups, the time-to-incident MALO was compared between 62 patients (68% female) who underwent metabolic surgery and 106 nonsurgical controls (71% female), with a mean follow-up of 10.0 ± 4.5 years. The 15 year cumulative incidence of MALO was 20.9% (95% confidence interval (CI), 2.5-35.9%) in the surgical group compared with 46.4% (95% CI, 25.6-61.3%) in the nonsurgical group, with an adjusted hazard ratio of 0.28 (95% CI, 0.12-0.64), P = 0.003. The 15 year cumulative incidence of decompensated cirrhosis was 15.6% (95% CI, 0-31.3%) in the surgical group compared with 30.7% (95% CI, 12.9-44.8%) in the nonsurgical group, with an adjusted hazard ratio of 0.20 (95% CI, 0.06-0.68), P = 0.01. Among patients with compensated MASH-related cirrhosis and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MALO. In the absence of approved medical therapies for compensated MASH-related cirrhosis, metabolic surgery may represent a safe and effective therapeutic option to influence the trajectory of cirrhosis.

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Conflict of interest statement

Competing interests: A. Aminian reported receiving research grants from Medtronic and Ethicon. He serves as a consultant for Medtronic, Ethicon and Eli Lilly. R.L. serves as a consultant or advisory board member for 89Bio, Alnylam, Arrowhead Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Cirius, CohBar, DiCerna, Galmed, Gilead, Glympse Bio, Intercept, Ionis, Metacrine, NGM Biopharmaceuticals, Novo Nordisk, Pfizer, Sagimet and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Novartis, Pfizer, pH Pharma and Siemens. He is also cofounder of Liponexus. A.J.S. has stock options in Genfit, Tiziana, Indalo, Durect, Inversago and Galmed. He has served as a consultant to AstraZeneca, Salix, Tobira, Takeda, Janssen, Gilead, Terns, Merck, Madrigal, NGM Biopharmaceuticals, Sagimet, Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Hemoshear, Novartis, Inventiva, Enyo, Akero, 89Bio, Novo Nordisk, Pfizer, Amgen, Genentech, Regeneron, Alnylam, Hanmi, LG Chem, Histoindex, Theratechnologies, Intercept, Target-RWE, Surrozen, Zydus, Path AI, Exhalenz and Genfit. His institution has received grant support from Gilead, Salix, Tobira, Bristol Myers Squibb, Pfizer, Intercept, Merck, AstraZeneca, Malinckrodt and Novartis. He receives royalties from Elsevier and UptoDate. N.A. has received research funding from 89Bio, Akero, AbbVie/Allergan, Better Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Corcept, Galectin, Genentech, Genfit, Gilead, Healio, Hepagene, Intercept, Inventiva, Ionis, Madrigal, Merck, NGM, Noom, NorthSea, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking and Zydus; has attended speaker bureaus for AbbVie/Allergan, Alexion, Echosens, Eisai, Exelixis, Gilead, Intercept, Perspectum, Salix and Theratechnologies; and has acted as a consultant for AbbVie/Allergan, Echosens, Gilead, Intercept, Madrigal, Novo Nordisk, Perspectum, Pfizer and Zydus. S.E.N. reported receiving grants to perform clinical trials from AbbVie, AstraZeneca, Amgen, Bristol Myers Squibb, Eli Lilly, Esperion Therapeutics Inc, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis and Silence Therapeutics. The other authors declare no competing interests.

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