Bariatric and metabolic surgery is more effective than medications and lifestyle interventions for the treatment of advanced non-alcoholic fatty liver disease, according to the outcomes of a randomised clinical trial by researchers from King's College London and the Catholic University of Rome. The study is the first to compare three active treatments of non-alcoholic steatohepatitis (NASH) and to specifically investigate the effectiveness of metabolic surgery in a randomised clinical trial. The findings were featured in the paper, ‘Bariatric–metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial’, published in The Lancet.
"The presence of NASH predicts a significant risk of complications and mortality in people with severe obesity and type 2 diabetes,” said Professor Francesco Rubino, a senior co-investigator and Chair of Bariatric and Metabolic Surgery at King's College London and consultant surgeon at King's College Hospital. “The results of this study provide a compelling case for prioritization of metabolic surgery in this patient population."
This multi-centre randomised trial was conducted at three major hospitals in Rome, Italy, and compared the efficacy of bariatric and metabolic surgery versus lifestyle modifications and best current medical care in 288 patients (aged 25–70 years with obesity (BMI 30–55 kg/m²), with or without type 2 diabetes), with histologically confirmed NASH. Patients were randomly assigned to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]) or sleeve gastrectomy (n=96 [33%]). The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at one-year follow-up.
Pre- and post-operative liver biopsies showed that surgery was more effective in inducing complete reversal of inflammation and cell damage in the liver - the core characteristics of NASH - without worsening of liver fibrosis after one year from surgery. The probability of achieving reversal of NASH was 3–5 times higher with metabolic surgery than with medical care. Surgery was also more effective at achieving improvement of at least one stage of liver fibrosis, another pre-specified endpoint of the trial. The two surgical procedures appeared to equally improve NASH.
In the intention-to-treat analysis, the percentage of participants who met the primary endpoint was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with lifestyle modification (15 [16%]; p<0·0001). The calculated probability of
NASH resolution was 3·60 times greater (95% CI 2·19–5·92; p<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (2·23–6·02; p<0·0001) in the sleeve gastrectomy group compared with in the lifestyle modification group.
In the per protocol analysis (236 [82%] participants who completed the trial), the primary endpoint was met in 54 (70%) of 77 participants in the Roux-en-Y gastric bypass group and 55 (70%) of 79 participants in the sleeve gastrectomy group, compared with 15 (19%) of 80 in the lifestyle modification group (p<0·0001).
Severe adverse events occurred in ten (6%) participants who had bariatric-metabolic surgery, but these participants did not require re-operations and severe adverse events were resolved with medical or endoscopic management. There were no deaths or life threatening complications reported in the study.
The researchers said the ability of surgery to control and even improve fibrosis associated with NASH is of special clinical relevance, as fibrosis is the main predictor of liver complications and poor cardiovascular outcomes and death in patients with NASH.
"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,” added Professor Geltrude Mingrone, first author of the report, Professor of Medicine at the Catholic University of Rome and a Professor of Diabetes and Nutrition at King's College London.
“This study showed that bariatric-metabolic surgery was more effective than lifestyle intervention and best medical care as a treatment of NASH in people with obesity, with or without type 2 diabetes,” the authors concluded. “Roux-en-Y gastric bypass and sleeve gastrectomy had similar efficacy on NASH, even though Roux-en-Y gastric bypass was generally more major risk factor for NAFLD and that the condition significantly increases the likelihood of developing NASH in comparison with the non-diabetic population.”
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