Bariatric surgery may be the go-to strategy for NASH in the obese

Bariatric surgery significantly lowers the risk of major adverse liver outcomes and major adverse cardiovascular events (MACE) – the dual primary endpoints – in obese patients with biopsy-driven nonalcoholic steatohepatitis (NASH) in the SPLENDOR* study.

This is a huge breakthrough for patients as currently there is no US FDA-approved pharmacotherapy to reduce the risk of severe outcomes or deaths in NASH. “This is the first study reporting a treatment modality that is associated with a decreased risk of major adverse events in patients with biopsy-proven NASH,” said senior author Dr Steven Nissen of the Heart, Vascular and Thoracic Institute, Cleveland Clinic, Ohio, US.

“In patients with NASH and obesity, the 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,” he pointed out.

“Bariatric surgery should be considered a first-line treatment for these patients,” commented Dr Shanu Kothari, a bariatric surgeon at Prisma Health in Greenville, South Carolina, US and president of the American Society for Metabolic & Bariatric Surgery, who is unaffiliated with the study.

Benefits persist for 10 years

Included in the SPLENDOR study were 1,158 patients with NASH but no cirrhosis – 650 underwent bariatric surgery and 508 served as controls.  The median age was 49.8 years, BMI was 44.1 kg/m², and about 64 percent were women. [JAMA 2021;326:2031-2042]

Bariatric procedures included Roux-en-Y gastric bypass and sleeve gastrectomy performed in 83 percent and 17 percent of the patients, respectively.

At a median follow-up of 7 years, five patients in the bariatric surgery group had experienced a major adverse liver event vs 40 patients in the nonsurgical controls.

At 10 years, the cumulative incidence of major adverse liver outcomes was 88 percent lower with bariatric surgery, occurring in 2.3 percent vs 9.6 percent in the nonsurgical group (hazard ratio [HR], 0.12; p= 0.01).

“By study end, 39 patients in the surgical group had experienced MACE vs 60 patients in the control group,” said Nissen. “After 10 years, the cumulative incidence of MACE was 70 percent lower with bariatric surgery at 8.5 percent, compared with 15.7 percent in the control group (HR, 0.30; p=0.007). 

Weight loss with surgery

Bariatric surgery also significantly reduced mean body weight by 22.4 percent in those who underwent the procedure vs 4.6 percent with the nonsurgical controls (p<0.001). Importantly, patients with diabetes also had a significant reduction in HbA_1c with bariatric surgery.

Within the first year after the procedure, four patients had died from surgical complications, including two who had a gastrointestinal leak.

NASH represents the progressive form of non-alcoholic fatty liver disease. “Obesity is the main pathophysiologic driver of NASH,” said the authors. “Bariatric surgery is the most effective available therapy for obesity, with significant reductions in major adverse liver and cardiovascular outcomes in the study.”