Surgery may be the most efficacious treatment for metabolic liver disease, according to new research led by King's College London (KCL). The study, published in the Lancet, was the first direct comparison of bariatric-metabolic surgery with lifestyle interventions plus medical therapy. Results confirmed observational studies that had suggested that such surgery might greatly improve non-alcoholic steatohepatitis (NASH).
The team undertook a 52-week, multicentre, open-label, randomised trial in 288 people aged 25-70 years with obesity (BMI 30-55 kg/m²) and biopsy-proven NASH, with or without type 2 diabetes. Participants were randomly assigned (1:1:1) to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy.
Of the 96 people in each group, the primary endpoint of histological resolution of NASH without worsening of fibrosis at 1-year follow-up was significantly higher in the Roux-en-Y gastric bypass group (54 [56%]) and sleeve gastrectomy group (55 [57%]) compared with the lifestyle modification group (15 [16%]; p<0·0001).
Tripled Resolution Rates With Surgery
The researchers said that the calculated probability of NASH resolution was 3·60 times greater (95% CI 2.19 to 5.92; P<0·0001) in the Roux-en-Y gastric bypass group and 3·67 times greater (95% CI 2.23 to 6.02; P<0·0001) in the sleeve gastrectomy group than in the lifestyle modification group.
No deaths or life-threatening complications were reported after surgery, although severe adverse events occurred in 10 (6%) participants, a similar rate after both surgical procedures. However they were all resolved with medical or endoscopic management and did not require re-operations.
The team commented that non-alcoholic fatty liver disease is the most common cause of chronic liver disease, globally affecting 55% of people with type 2 diabetes and 75% of those with obesity. NASH is its progressive form, which, left untreated, can lead to liver failure and liver cancer – it is one of the leading causes of liver transplant in the western world.
NASH currently affects 12% of adults in the UK and increases risk of cardiovascular disease and overall mortality in patients with obesity or type 2 diabetes. At least 10% bodyweight loss is necessary to achieve clinically significant rates of NASH resolution, but this is "rarely attainable with lifestyle interventions alone", the researchers said. In contrast, bariatric-metabolic surgery can induce long-term weight reduction of up to 30%, along with substantial amelioration or even long-term remission of type 2 diabetes.
The team concluded that their study results 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". They noted that resolution of NASH in the surgery groups was also associated with postoperative improvement of insulin resistance and triglyceride concentrations.
'Compelling Case' for Prioritisation of Metabolic Surgery
In addition, other research has shown that bariatric-metabolic surgery in individuals with NASH was cost-effective in all individuals with obesity and NASH, regardless of fibrosis stage, "making surgery a suitable approach for the treatment of this condition". Diabetes UK guidance says that bariatric surgery "can be a very effective way of losing weight and putting type 2 diabetes into remission" and that it could be "cost-effective for the NHS".
Bariatric surgery is currently available on the NHS for selected people with a BMI of 40 or more, or a BMI of 35-40 and an obesity-related condition that might improve with weight loss, provided other weight-loss methods have failed.
Senior co-investigator professor Francesco Rubino, chair of bariatric and metabolic surgery at KCL, said: "The presence of NASH predicts a significant risk of complications and mortality in people with severe obesity and type 2 diabetes. The results of this study provide a compelling case for prioritisation of metabolic surgery in this patient population".
Funding was provided by the Fondazione Policlinico Universitario A Gemelli, Policlinico Universitario Umberto I, and S Camillo Hospital, Rome, Italy.