Weight Loss Surgery 'Best Treatment' for Fatty Liver Disease

Pam Harrison

November 23, 2021

Weight loss surgery significantly lowers the risk of major adverse liver outcomes as well as major acute cardiovascular events (MACE) in patients with biopsy-proven nonalcoholic steatohepatitis (NASH), compared with similar patients who didn't have surgery, new research shows.

"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," senior author Steven Nissen, MD, of the Heart, Vascular and Thoracic Institute, Cleveland Clinic, Ohio, said in a statement from the hospital.

"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," he emphasized.

The study was published online November 11 in JAMA.


The Surgical Procedures and Long-Term Effectiveness in NASH Disease and Obesity Risk (SPLENDOR) study included 1158 patients with biopsy-proven NASH without cirrhosis; 650 underwent bariatric surgery and the remaining 508 served as controls. Participants were a median age of 49.8 years, had a median body mass index (BMI) of 44.1 kg/m2, and almost 64% were women.

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

"The prespecified primary endpoints were the incidence of major adverse liver outcomes and MACE," lead author Ali Aminian, MD, director, Bariatric & Metabolic Institute, Cleveland Clinic, Ohio, notes. Major adverse liver events included progression to clinical or histological cirrhosis, development of liver cancer, need for liver transplantation, or liver-related death.

MACE was a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death.

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

At 10 years, the cumulative incidence of major adverse liver outcomes was 88% lower in the bariatric surgery group, occurring in 2.3% of the surgical group, compared with 9.6% in the nonsurgical group (hazard ratio [HR], 0.12; P = .01), the investigators report.

By study end, 39 patients in the surgical group had experienced MACE compared with 60 patients in the control group. After 10 years, the cumulative incidence of MACE was 70% lower in the bariatric surgery group, at 8.5%, versus 15.7% in the control group (HR, 0.30; P = .007). 

Again at 10 years, bariatric surgery also reduced mean body weight by 22.4% among those who had undergone an operation compared with weight loss, on average, of 4.6% among nonsurgical controls (P < .001), while among patients with diabetes, bariatric surgery also led to a significant reduction in A1c.

However, the risk of major adverse events within 30 days of bariatric surgery was relatively high, at 9.5%, the authors note.

But within the first year after undergoing the procedure, only four patients (0.6%) had died from surgical complications, including two patients from a gastrointestinal leak.

Primary Treatment for NASH Is Weight Loss

As the authors point out, obesity is the main pathophysiologic driver of NASH and weight loss — however achieved — is currently the primary treatment for NASH.

"However, bariatric surgery is the most effective available therapy for obesity," they stress.

Shanu Kothari, MD, president of the American Society for Metabolic & Bariatric Surgery, agrees, saying in a statement: "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 as first-line treatment for these patients," he stressed.

And as pointed out by Aminian, there is currently no FDA-approved medication for the treatment of fatty liver.

"The striking findings of this study provide strong evidence that bariatric surgery should be considered as an effective therapeutic option for patients with advanced fatty liver and obesity," he added in the statement.

Aminian has reported receiving research support and speaking honoraria from Medtronic. Nissen has reported receiving research support from Medtronic and Ethicon.

JAMA. Published online November 11, 2021. Abstract

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