BACKGROUND AND PURPOSE:

• Observational studies have suggested that non-alcoholic steatohepatitis (NASH) may be significantly improved by bariatric–metabolic surgery
• Verrastro et al. (The Lancet, 2023) compared the efficacy and safety of bariatric-metabolic surgery with lifestyle intervention plus best medical care as a treatment of NASH

METHODS:

• Multicenter, open-label, randomized trial
• Participants
  • 25 to 70 years
  • Obesity, with or without type 2 diabetes
  • Histologically confirmed NASH
• Interventions
  • Lifestyle modification plus best medical care
  • Roux-en-Y gastric bypass
  • Sleeve gastrectomy
• Study design
  • 1:1:1 randomization
  • Obesity: BMI≥30 or 27.5 kg/m2 if Asian descent
  • Hepatopathologists performing biopsies were blinded
  • 80% power, with type I error, set to 0.05 | sample size 77 in each group, with final total of 288 participants to account for 20% attrition rate
• Primary outcome
  • Histological resolution of NASH without worsening of fibrosis at 1-year follow-up

RESULTS:

• Lifestyle modification: 96 patients | Roux-en-Y gastric bypass: 96 | Sleeve gastrectomy: 96
• In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in both surgery groups compared to lifestyle modification (P<0.0001)
  • Lifestyle modification: 16%
  • The Roux-en-Y gastric bypass group: 56%
  • The sleeve gastrectomy group: 57%
• The calculated probability of NASH resolution was also higher in these groups
  • Roux-en-Y gastric bypass group
    • 3.60 times greater (95% CI 2.19 to 5.92) | P<0.0001
  • Sleeve gastrectomy group
    • 3.67 times greater (95% CI, 2.23 to 6.02) | P<0.0001
• In the per protocol analysis, the percentage of participants who met the primary outcome remained higher in the surgery groups (P<0.0001)
  • Lifestyle modification: 19%
  • The Roux-en-Y gastric bypass group: 70%
  • The sleeve gastrectomy group: 70%
• No deaths or life-threatening complications were reported
• Severe adverse events occurred in 6% of bariatric-metabolic surgery participants
  • These individuals did not need re-operations and severe events resolved with medical or endoscopic management

CONCLUSION:

• Treatment of NASH is more effective with bariatric-metabolic surgery than with lifestyle modification and optimized medical therapy
• The authors state

Novel anti-obesity drugs might result in better NASH outcomes than those we observed in the non-surgical group of our study, given their greater weight-loss potential

Future research should compare new anti-obesity drugs with other active drugs or bariatric-metabolic surgery

Learn More – Primary Sources:

Bariatric–metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial