Association of Bariatric Surgery With Adverse Outcomes in Patients With Nonalcoholic Steatohepatitis | Bariatric Surgery | JN Learning | AMA Ed Hub [Skip to Content]
Outline
Quiz
PDF
Hepatobiliary Disease

Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis

Educational Objective
To understand the association of bariatric surgery with major adverse liver outcomes and major adverse cardiovascular events in patients who have nonalcoholic steatohepatitis and obesity.
1 Credit CME
JAMA
November 23, 2021
Original Investigation
Ali Aminian, MD1;
Abbas Al-Kurd, MD1;
Rickesha Wilson, MD1;
James Bena, MS2;
Hana Fayazzadeh, MD1;
Tavankit Singh, MD3,4;
Vance L. Albaugh, MD, PhD1,5;
Faiz U. Shariff, MD1,6;
Noe A. Rodriguez, MD1,7;
Jian Jin, MS2;
Stacy A. Brethauer, MD, MBA1,8;
Srinivasan Dasarathy, MD3;
Naim Alkhouri, MD3,9;
Philip R. Schauer, MD1,5;
Arthur J. McCullough, MD3;
Steven E. Nissen, MD10
Author Affiliations
  • 1Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, Ohio
  • 2Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
  • 3Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio
  • 4Department of Gastroenterology and Hepatology, Allegheny General Hospital, Pittsburgh, Pennsylvania
  • 5Bariatric and Metabolic Institute, Pennington Biomedical Research Center, Baton Rouge, Louisiana
  • 6Department of Surgery, Wellspan Hospital, York, Pennsylvania
  • 7Department of Surgery, Northwest Medical Center, Springdale, Arkansas
  • 8Department of Surgery, Wexner Medical Center, Ohio State University, Columbus
  • 9Fatty Liver Program, Arizona Liver Health, Chandler
  • 10Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
Read article on JAMA Network

MOC/CME Information

editorial comment icon
Editorial
Comment
 related articles icon
Related
Articles
 author interview icon
Interviews
 multimedia icon
Multimedia
Read Article Take Quiz
Key Points

Question  Is there an association between bariatric surgery and major adverse liver outcomes or major adverse cardiovascular events in patients with nonalcoholic steatohepatitis and obesity in long-term follow-up?

Findings  In this retrospective cohort study of 1158 patients (including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group) with biopsy-proven fibrotic nonalcoholic steatohepatitis without cirrhosis, bariatric surgery was significantly associated with a lower risk of major adverse liver outcomes (adjusted absolute 10-year risk difference of 12.4%) and major adverse cardiovascular events (adjusted absolute 10-year risk difference of 13.9%).

Meaning  Among patients with nonalcoholic steatohepatitis and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and major adverse cardiovascular events.

Abstract

Importance  No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH).

Objective  To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis.

Design, Setting, and Participants  In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021.

Exposures  Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care.

Main Outcomes and Measures  The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework.

Results  A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2).

Conclusions and Relevance  Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Related Articles

  1. Cost-effectiveness of Bariatric Surgery for Patients With NASH Cirrhosis

  2. Nonalcoholic Steatohepatitis—A Review
    1.00 CME

  3. Bariatric Surgery as a Strategy for Improving Outcomes in Nonalcoholic Steatohepatitis

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

See More About

Bariatric Surgery Obesity Surgery Hepatobiliary Disease Gastroenterology and Hepatology
Article Information

Corresponding Author: Steven E. Nissen, MD, Cleveland Clinic, 9500 Euclid Ave, Desk JB-20, Cleveland, OH 44195 (nissens@ccf.org).

Accepted for Publication: October 14, 2021.

Published Online: November 11, 2021. doi:10.1001/jama.2021.19569

Author Contributions: Dr Aminian had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Aminian, Al-Kurd, Fayazzadeh, Dasarathy, Schauer.

Acquisition, analysis, or interpretation of data: Aminian, Al-Kurd, Wilson, Bena, Singh, Albaugh, Shariff, Rodriguez, Jin, Brethauer, Dasarathy, Alkhouri, Schauer, McCullough, Nissen.

Drafting of the manuscript: Aminian, Fayazzadeh, Albaugh, Shariff, Jin, Nissen.

Critical revision of the manuscript for important intellectual content: Aminian, Al-Kurd, Wilson, Bena, Singh, Albaugh, Shariff, Rodriguez, Brethauer, Dasarathy, Alkhouri, Schauer, McCullough, Nissen.

Statistical analysis: Al-Kurd, Bena, Alkhouri.

Administrative, technical, or material support: Aminian, Wilson, Fayazzadeh, Albaugh, Shariff, Dasarathy, Schauer, McCullough, Nissen.

Supervision: Aminian, Dasarathy, Nissen.

Conflict of Interest Disclosures: Dr Aminian reported receiving research support and speaking honoraria from Medtronic. Dr Brethauer reported being a consultant for GI Windows and receiving speaking honoraria from Medtronic. Dr Dasarathy reported being supported by research grants from the National Institutes of Health. Dr Alkhouri reported being on an advisory board or review panel for Echosens, Fibronostics, Gilead, Intercept, Perspectum, Pfizer, and Zydus; receiving research support from 89Bio, Akero, Bristol-Myers Squibb, Genentech, Gilead, Intercept, Madrigal, NGM Bio, Novo Nordisk, Pfizer, Viking, and Zydus; and being a speaker for AbbVie, Alexion Echosens, Gilead, and Intercept. Dr Schauer reported being a consultant for GI Dynamics, Keyron, Persona, and Mediflix; receiving research support from Ethicon, Medtronic, and Pacira; receiving honoraria from Ethicon, Medtronic, BD Surgical, and Gore; and having an ownership interest in SE Healthcare LLC. Dr Nissen reported receiving research support from Medtronic and Ethicon. No other disclosures were reported.

Meeting Presentation: This study was presented in part in the Latest Science Session at the European Society of Cardiology Congress on August 27, 2021.

Additional Contributions: We acknowledge Mary Ellen Satava, BSN (Cleveland Clinic), for her help in collecting some of the data. She did not receive compensation for her role in the study.

References
1.
Powell  EE , Wong  VW , Rinella  M .  Non-alcoholic fatty liver disease.   Lancet. 2021;397(10290):2212-2224. doi:10.1016/S0140-6736(20)32511-3PubMedGoogle ScholarCrossref
2.
Sheka  AC , Adeyi  O , Thompson  J , Hameed  B , Crawford  PA , Ikramuddin  S .  Nonalcoholic steatohepatitis: a review.   JAMA. 2020;323(12):1175-1183. doi:10.1001/jama.2020.2298PubMedGoogle ScholarCrossref
3.
Diehl  AM , Day  C .  Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis.   N Engl J Med. 2017;377(21):2063-2072. doi:10.1056/NEJMra1503519PubMedGoogle ScholarCrossref
4.
Ferguson  D , Finck  BN .  Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus.   Nat Rev Endocrinol. 2021;17(8):484-495. doi:10.1038/s41574-021-00507-zPubMedGoogle ScholarCrossref
5.
Stahl  EP , Dhindsa  DS , Lee  SK , Sandesara  PB , Chalasani  NP , Sperling  LS .  Nonalcoholic fatty liver disease and the heart: JACC state-of-the-art review.   J Am Coll Cardiol. 2019;73(8):948-963. doi:10.1016/j.jacc.2018.11.050PubMedGoogle ScholarCrossref
6.
Mingrone  G , Panunzi  S , De Gaetano  A ,  et al.  Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial.   Lancet. 2021;397(10271):293-304. doi:10.1016/S0140-6736(20)32649-0PubMedGoogle ScholarCrossref
7.
Schauer  PR , Bhatt  DL , Kirwan  JP ,  et al; STAMPEDE Investigators.  Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes.   N Engl J Med. 2017;376(7):641-651. doi:10.1056/NEJMoa1600869PubMedGoogle ScholarCrossref
8.
Ikramuddin  S , Korner  J , Lee  WJ ,  et al.  Lifestyle intervention and medical management with vs without Roux-en-Y gastric bypass and control of hemoglobin A1c, LDL cholesterol, and systolic blood pressure at 5 years in the Diabetes Surgery Study.   JAMA. 2018;319(3):266-278. doi:10.1001/jama.2017.20813PubMedGoogle ScholarCrossref
9.
Schiavon  CA , Bersch-Ferreira  AC , Santucci  EV ,  et al.  Effects of bariatric surgery in obese patients with hypertension: the GATEWAY randomized trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension).   Circulation. 2018;137(11):1132-1142. doi:10.1161/CIRCULATIONAHA.117.032130PubMedGoogle ScholarCrossref
10.
Lassailly  G , Caiazzo  R , Ntandja-Wandji  LC ,  et al.  Bariatric surgery provides long-term resolution of nonalcoholic steatohepatitis and regression of fibrosis.   Gastroenterology. 2020;159(4):1290-1301.e5. doi:10.1053/j.gastro.2020.06.006PubMedGoogle ScholarCrossref
11.
Manco  M , Mosca  A , De Peppo  F ,  et al.  The benefit of sleeve gastrectomy in obese adolescents on nonalcoholic steatohepatitis and hepatic fibrosis.   J Pediatr. 2017;180:31-37.e2. doi:10.1016/j.jpeds.2016.08.101PubMedGoogle ScholarCrossref
12.
Mattar  SG , Velcu  LM , Rabinovitz  M ,  et al.  Surgically-induced weight loss significantly improves nonalcoholic fatty liver disease and the metabolic syndrome.   Ann Surg. 2005;242(4):610-617. doi:10.1097/01.sla.0000179652.07502.3fPubMedGoogle ScholarCrossref
13.
Aminian  A , Zajichek  A , Arterburn  DE ,  et al.  Association of metabolic surgery with major adverse cardiovascular outcomes in patients with type 2 diabetes and obesity.   JAMA. 2019;322(13):1271-1282. doi:10.1001/jama.2019.14231PubMedGoogle ScholarCrossref
14.
Sjöström  L , Peltonen  M , Jacobson  P ,  et al.  Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications.   JAMA. 2014;311(22):2297-2304. doi:10.1001/jama.2014.5988PubMedGoogle ScholarCrossref
15.
Fisher  DP , Johnson  E , Haneuse  S ,  et al.  Association between bariatric surgery and macrovascular disease outcomes in patients with type 2 diabetes and severe obesity.   JAMA. 2018;320(15):1570-1582. doi:10.1001/jama.2018.14619PubMedGoogle ScholarCrossref
16.
Kleiner  DE , Brunt  EM , Van Natta  M ,  et al; Nonalcoholic Steatohepatitis Clinical Research Network.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease.   Hepatology. 2005;41(6):1313-1321. doi:10.1002/hep.20701PubMedGoogle ScholarCrossref
17.
Thomas  LE , Li  F , Pencina  MJ .  Overlap weighting: a propensity score method that mimics attributes of a randomized clinical trial.   JAMA. 2020;323(23):2417-2418. doi:10.1001/jama.2020.7819PubMedGoogle ScholarCrossref
18.
Li  F , Morgan  KL , Zaslavsky  AM .  Balancing covariates via propensity score weighting.   J Am Stat Assoc. 2018;113(521):390-400. doi:10.1080/01621459.2016.1260466Google ScholarCrossref
19.
Heinze  G , Schemper  M .  A solution to the problem of monotone likelihood in Cox regression.   Biometrics. 2001;57(1):114-119. doi:10.1111/j.0006-341X.2001.00114.xPubMedGoogle ScholarCrossref
20.
van Buuren  S .  Multiple imputation of discrete and continuous data by fully conditional specification.   Stat Methods Med Res. 2007;16(3):219-242. doi:10.1177/0962280206074463PubMedGoogle ScholarCrossref
21.
Rubin  DB .  Inference and missing data.   Biometrika. 1976;63(3):581-592. doi:10.1093/biomet/63.3.581Google ScholarCrossref
22.
Austin  PC .  Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies.   Pharm Stat. 2011;10(2):150-161. doi:10.1002/pst.433PubMedGoogle ScholarCrossref
23.
VanderWeele  TJ , Ding  P .  Sensitivity analysis in observational research: introducing the E-value.   Ann Intern Med. 2017;167(4):268-274. doi:10.7326/M16-2607PubMedGoogle ScholarCrossref
24.
Sanyal  AJ , Chalasani  N , Kowdley  KV ,  et al; NASH CRN.  Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.   N Engl J Med. 2010;362(18):1675-1685. doi:10.1056/NEJMoa0907929PubMedGoogle ScholarCrossref
25.
Neuschwander-Tetri  BA , Loomba  R , Sanyal  AJ ,  et al; NASH Clinical Research Network.  Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial.   Lancet. 2015;385(9972):956-965. doi:10.1016/S0140-6736(14)61933-4PubMedGoogle ScholarCrossref
26.
Armstrong  MJ , Gaunt  P , Aithal  GP ,  et al; LEAN Trial Team.  Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study.   Lancet. 2016;387(10019):679-690. doi:10.1016/S0140-6736(15)00803-XPubMedGoogle ScholarCrossref
27.
Newsome  PN , Buchholtz  K , Cusi  K ,  et al; NN9931-4296 Investigators.  A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis.   N Engl J Med. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395PubMedGoogle ScholarCrossref
28.
Heart Outcomes Prevention Evaluation Study Investigators.  Vitamin E supplementation and cardiovascular events in high-risk patients.   N Engl J Med. 2000;342:154-160. doi:10.1056/NEJM200001203420302Google ScholarCrossref
29.
Eslam  M , Alvani  R , Shiha  G .  Obeticholic acid: towards first approval for NASH.   Lancet. 2019;394(10215):2131-2133. doi:10.1016/S0140-6736(19)32963-0PubMedGoogle ScholarCrossref
30.
Matteoni  CA , Younossi  ZM , Gramlich  T , Boparai  N , Liu  YC , McCullough  AJ .  Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.   Gastroenterology. 1999;116(6):1413-1419. doi:10.1016/S0016-5085(99)70506-8PubMedGoogle ScholarCrossref
31.
Aminian  A , Kashyap  SR , Wolski  KE ,  et al.  Patient-reported outcomes after metabolic surgery versus medical therapy for diabetes: insights from the STAMPEDE randomized trial.   Ann Surg. 2021;274(3):524-532. doi:10.1097/SLA.0000000000005003PubMedGoogle ScholarCrossref
32.
English  WJ , DeMaria  EJ , Hutter  MM ,  et al.  American Society for Metabolic and Bariatric Surgery 2018 estimate of metabolic and bariatric procedures performed in the United States.   Surg Obes Relat Dis. 2020;16(4):457-463. doi:10.1016/j.soard.2019.12.022PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Privacy Policy|Terms of Use
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close
Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue