Background Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial.Methods We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m(2)), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365.Findings Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). 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). No deaths or life -threatening complications were reported in this study. 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.Interpretation Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH.

Verrastro, O., Panunzi, S., Castagneto-Gissey, L., De Gaetano, A., Lembo, E., Capristo, E., Guidone, C., Angelini, G., Pennestrì, F., Sessa, L., Vecchio, F. M., Riccardi, L., Zocco, M. A., Boskoski, I., Casella-Mariolo, J. R., Marini, P., Pompili, M., Casella, G., Fiori, E., Rubino, F., Bornstein, S. R., Raffaelli, M., Mingrone, G., Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial, <<THE LANCET>>, 2023; 401 (10390): 1786-1797. [doi:10.1016/S0140-6736(23)00634-7] [https://hdl.handle.net/10807/271734]

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

Verrastro, Ornella;Panunzi, Simona;Lembo, Erminia;Capristo, Esmeralda;Guidone, Caterina;Angelini, Giulia;Sessa, Luca;Vecchio, Fabio Maria;Riccardi, Laura;Zocco, Maria Assunta;Boskoski, Ivo;Pompili, Maurizio;Raffaelli, Marco;Mingrone, Geltrude
2023

Abstract

Background Observational studies suggest that bariatric-metabolic surgery might greatly improve non-alcoholic steatohepatitis (NASH). However, the efficacy of surgery on NASH has not yet been compared with the effects of lifestyle interventions and medical therapy in a randomised trial.Methods We did a multicentre, open-label, randomised trial at three major hospitals in Rome, Italy. We included participants aged 25-70 years with obesity (BMI 30-55 kg/m(2)), with or without type 2 diabetes, with histologically confirmed NASH. We randomly assigned (1:1:1) participants to lifestyle modification plus best medical care, Roux-en-Y gastric bypass, or sleeve gastrectomy. The primary endpoint of the study was histological resolution of NASH without worsening of fibrosis at 1-year follow-up. This study is registered at ClinicalTrials.gov, NCT03524365.Findings Between April 15, 2019, and June 21, 2021, we biopsy screened 431 participants; of these, 103 (24%) did not have histological NASH and 40 (9%) declined to participate. We randomly assigned 288 (67%) participants with biopsy-proven NASH to lifestyle modification plus best medical care (n=96 [33%]), Roux-en-Y gastric bypass (n=96 [33%]), or sleeve gastrectomy (n=96 [33%]). 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). No deaths or life -threatening complications were reported in this study. 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.Interpretation Bariatric-metabolic surgery is more effective than lifestyle interventions and optimised medical therapy in the treatment of NASH.
2023
Inglese
Verrastro, O., Panunzi, S., Castagneto-Gissey, L., De Gaetano, A., Lembo, E., Capristo, E., Guidone, C., Angelini, G., Pennestrì, F., Sessa, L., Vecchio, F. M., Riccardi, L., Zocco, M. A., Boskoski, I., Casella-Mariolo, J. R., Marini, P., Pompili, M., Casella, G., Fiori, E., Rubino, F., Bornstein, S. R., Raffaelli, M., Mingrone, G., Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis (BRAVES): a multicentre, open-label, randomised trial, <<THE LANCET>>, 2023; 401 (10390): 1786-1797. [doi:10.1016/S0140-6736(23)00634-7] [https://hdl.handle.net/10807/271734]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/271734
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