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

Abstract

IMPORTANCENo 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 PARTICIPANTSIn 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 MEASURESThe 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 s...

Review article: current and emerging therapies for the management of cirrhosis and its complications

“…A prospective French study conducted among 180 severely obese patients with biopsy‐proven NASH who underwent bariatric surgery revealed that 84% of patients had resolution of NASH 5 years after surgery 39 . A retrospective U.S. study of 1158 patients with biopsy‐proven NASH compared 650 patients who underwent bariatric surgery with 508 patients who were managed non‐surgically and determined that bariatric surgery was associated with a lower risk of major adverse liver outcomes defined by diagnostic codes (adjusted absolute risk difference 12.4%) 40 . Owing to the exclusion of large numbers of patients with cirrhosis, data are insufficient for bariatric surgery to be routinely recommended for patients with NASH cirrhosis and obesity.…”

“…39 A retrospective U.S. study of 1158 patients with biopsy-proven NASH compared 650 patients who underwent bariatric surgery with 508 patients who were managed non-surgically and determined that bariatric surgery was associated with a lower risk of major adverse liver outcomes defined by diagnostic codes (adjusted absolute risk difference 12.4%). 40 Owing to the exclusion of large numbers of patients with cirrhosis, data are insufficient for bariatric surgery to be routinely recommended for patients with NASH cirrhosis and obesity. Additional data to define the population most likely to benefit are urgently needed.…”

Diabetes and Fatty Liver

“…Bariatric surgery for pronounced obesity or moderate obesity and type 2 diabetes causes a pronounced reduction in the liver lipid con-tent as well as weight loss, although effects on inflammation and fibrosis of the liver have not yet been sufficiently investigated [5]. However, recently in the SPLENDOR study, among patients with NASH and obesity, bariatric surgery was associated with lower risk of adverse liver outcomes and major adverse cardiovascular events, compared to nonsurgical management [13].…”

Acute Liver Injury and Acute Liver Failure following Bariatric Surgery

“…Bariatric surgery is the most effective modality for reducing obesity-related comorbidities [ 1 , 2 , 3 ]. The goal of bariatric surgery is to maximize weight loss while retaining nutritional health, by preventing postoperative malnutrition and loss of lean body mass.…”

“…Bariatric procedures are categorized as either restrictive (limiting stomach capacity), malabsorptive (bypassing a portion of the small intestines), or a combination of both. Weight loss after bariatric surgery generally has a beneficial effect on the hepatic complications of obesity, with improvement of steatosis, inflammation, and fibrosis [ 3 ]. However, a combination of malnutrition, malabsorption, and a compromised intestinal barrier function after surgery occasionally also results in the deterioration of liver function [ 4 , 5 ].…”