OR WAIT null SECS
Data from the BRAVES trial indicates 70% of patients undergoing metabolic or bariatric surgery with histologically confirmed NASH achieved resolution at 52 weeks.
Undergoing bariatric or metabolic surgery could be the most effective means of achieving histologic resolution of non-alcoholic steatohepatitis (NASH), according to new trial data.
Results of the randomized, open-label trial, which included more than 280 patients with a history of NASH, suggest undergoing bariatric or metabolic surgery was associated with a more than 3-fold increase in likelihood of NASH resolution compared to lifestyle intervention, with per-protocol analysis indicating 70% of patients randomized to surgery achieved resolution.
“The results of our study support the use of metabolic surgery as a treatment of NASH, a condition for long considered orphan of effective therapies,” said lead investigator Geltrude Mingrone, MD, PhD, professor of Medicine at the Catholic University of Rome and professor of Diabetes and Nutrition at King’s College London.2
Named the Bariatric–metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES) trial, the multicenter, open-label, randomized trial was conducted at 3 major hospitals in Italy. Designed with the intent of evaluating the efficacy of surgery on NASH relative to lifestyle interventions, the trial randomized participants in a 1:1:1 ratio to lifestyle modification plus best medical care, Roux-en-Y gastric bypass (RYGB), or sleeve gastrectomy.1
Per trial protocol, best medical care included daily vitamin E supplementation at 800 IU per day and their choice of vitamin E, pioglitazone, and liraglutide as add-on lifestyle medication based on evidence of their positive effects in NASH. Investigators noted those with diabetes received pioglitazone and a GLP1-RA, plus SGLT2-inhibitors or other anti-diabetes medications as needed.1
For the purpose of analysis, the primary outcome of interest was defined as the histological resolution of NASH without worsening of fibrosis the 1-year follow-up.1
Inclusion criteria for the trial were having obesity, with or without type 2 diabetes, with histologically confirmed NASH and no evidence of another form of liver disease. Investigators defined obesity as a BMI of 30-55 kg/m2 and histologically confirmed NASH as non-alcoholic fatty liver disease (NAFLD) activity score of at least 1 in each single item.1
From April 15, 2019-June 21, 2021, a total of 431 patients underwent biopsy screening. Of these, 103 did not have histological NASH and 40 declined to participate. Of the 288 who underwent randomization, 96 were randomized to lifestyle modification, 96 were randomized to RYGB, and 96 were randomized to sleeve gastrectomy.1
In an intention-to-treat analysis, results indicated the rate of NASH resolution was significantly higher in both the RYGB (56%) and the sleeve gastrectomy group (57%) compared with the lifestyle modification group (16%) (P <.0001), with further analysis suggesting the probability of resolution was 3.6-fold greater (95% CI, 2.19-5.92; P <.0001) in the RYGB group and 3.67-fold greater (95% CI, 2.23-6.02; P <.0001) compared with lifestyle modification. In a per-protocol analysis, which included 82% of participants who underwent randomization, NASH resolution was achieved by 70% of the RYGB group, 70% of the sleeve gastrectomy group, and 19% of the lifestyle modification group (P <.0001).1
Investigators pointed out there were no deaths or life-threatening complications reported during the study. Additional safety analysis indicated a total of 10 participants in the surgery groups experienced a serious adverse event, but none of these required reoperation and were resolved with medical or endoscopic management.1
“The presence of NASH predicts a significant risk of complications and mortality in people with severe obesity and type 2 diabetes,” added senior investigator Francesco Rubino, MD, chair of Bariatric and Metabolic Surgery at King’s College London and consultant surgeon at King’s College Hospital.2 “The results of this study provide a compelling case for prioritization of metabolic surgery in this patient population”.