In patients with biopsy-proven NASH, the SPLENDOR study is the first to report a medical modality associated with decreased risk of major adverse events.
Bariatric surgery among patients with obesity and nonalcoholic steatohepatitis (NASH) significantly lowered the risk of adverse liver outcomes and major adverse cardiovascular events (MACE) vs nonsurgical management according to results from a recent Cleveland Clinic study published online in JAMA.
Ali Aminian, MD | Cleveland Clinic
Specifically, the investigators report that undergoing bariatric surgery was associated with an 88% reduction in risk of progression of fatty liver to cirrhosis, liver cancer, or liver-related death and with a 70% reduction in risk for MACE. In the absence of approved pharmacotherapy for fatty liver disease, according to lead investigator Ali Aminian, MD, director of Cleveland Clinic’s Bariatric & Metabolic Institute, the findings provide support for bariatric surgery as a therapeutic option for this high-risk population.
“The SPLENDOR study shows that in patients with obesity and NASH, substantial and sustained weight loss achieved with bariatric surgery can simultaneously protect the heart and decrease the risk of progression to end-stage liver disease,” said study senior investigator, Steven Nissen, MD, chief academic officer of the Heart, Vascular and Thoracic Institute at Cleveland Clinic, in a Clinic statement. “This is the first study in the medical field reporting a treatment modality that is associated with decreased risk of major adverse events in patients with biopsy-proven NASH.”
To compare the effects of bariatric surgery with nonsurgical management of obesity in patients with NASH, Cleveland Clinic investigators drew on data from the Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk (SPLENDOR) study. SPLENDOR, which was designed to assess the long-term associations between bariatric surgery and future risk of progression to cirrhosis and MACE, collected data from 25 828 patients who had a liver biopsy performed between 2004 and 2016 and were followed through March 2021.
Of the 25 828 patients for whom liver biopsy data were available, 1158 fulfilled enrollment criteria, including having clinical obesity and confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). The final study sample was 63.9% women, had a median age of 49.8 years, and median BMI of kg/m2; 650 patients underwent bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) and 508 received nonsurgical care. The median follow-up for all patients was 7 years. After overlap weighting, the researchers report, distribution of baseline covariates, including histological severity of liver injury, was well-balanced.
Primary outcomes of interest for Aminian and colleagues were the incidence of major adverse liver outcomes and MACE. Major adverse liver outcomes included progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality. MACE was defined as a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death. Associations with bariatric surgery were estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework.
“No treatment other than bariatric surgery has been shown to have such a significant effect in reducing the risk of severe outcomes or death in patients with NASH. Bariatric surgery should be considered a first-line treatment for these patients.”
At the end of the follow-up period, in the unweighted data set, 5 patients who received bariatric surgery and 40 in the nonsurgical group experienced major adverse hepatic outcomes, according to the study. MACE in the unweighted data set was experienced among 39 patients in the bariatric surgery group and among 60 who did not undergo surgery.
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 [ARD], 12.4% [95% CI, 5.7-19.7]; aHR, 0.12 [95% CI, 0.02-0.63]; P=.01). The cumulative incidence of MACE assessed at 10 years in the bariatric surgery group was 8.5% (95% CI, 5.5%-11.4%) and 15.7% (95% CI, 11.3-19.8) in the nonsurgical group (adjusted ARD, 13.9% [95% CI, 5.9-21.9]; aHR, 0.30 [95% CI, 0.12-0.72]; P=.007).
The investigators report that 4 patients (0.6%) died from surgical complications, including 2 with gastrointestinal leak and 2 with respiratory failure, within the first year of bariatric surgery.
“No treatment other than bariatric surgery has been shown to have such a significant effect in reducing the risk of severe outcomes or death in patients with NASH,” said Shanu N. Kothari, MD, president of the American Society for Metabolic and Bariatric Surgery, in a ASMBS statement. “Bariatric surgery should be considered a first-line treatment for these patients.”
Reference: Aminian A, Al-Kurd A, Wilson R, et al. Association of bariatric surgery with major adverse liver and cardiovascular outcomes in patients with biopsy-proven nonalcoholic steatohepatitis. JAMA. 2021;326:2031-2042. doi:10.1001/jama.2021.19569
