Cheng Han Ng1, Mark D Muthiah1,2,3, Jieling Xiao1, Yip Han Chin1, Grace Lim4, Wen Hui Lim1, Phoebe Tay1, Darren Jun Hao Tan1, Jie Ning Yong1, Xin-Hui Pan1, Jeffery Wei Heng Koh1, Nicholas Chew1, Nicholas Syn1, Eunice Tan1,2,3, Daniel Q Huang1,2,3, Mohammad Shadab Siddiqui5, Rohit Loomba6, Arun J Sanyal5, Mazen Noureddin7. 1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 2. Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore. 3. National University Centre for Organ Transplantation, National University Health System, Singapore. 4. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. 5. Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA. 6. NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, San Diego, California, USA. 7. Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Centre, Los Angeles, California, USA.
Abstract
BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is the most common cause of liver disease. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs. APPROACH AND RESULTS: Medline, EMBASE and CENTRAL were searched for randomised controlled trials evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, at least 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and at least 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis. Among 49 included trials, treatments modulating energy (Risk ratio (RR): 1.92, Credible intervals (Crl): 1.59-2.34) were most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.66, Crl: 0.65-4.50), bile acids (RR: 1.37, Crl: 0.99-1.92) and inflammation (RR: 1.00, Crl: 0.75-1.33). Energy and bile acids modulation were effective in at least 2-point NAS reduction without worsening of fibrosis (RR: 1.52, Crl 1.30-1.77; RR: 1.69, Crl 1.41-2.03) and at least 1-point reduction in fibrosis (RR: 1.26, Crl:1.05-1.49; RR: 1.54, Crl: 1.20-1.97). CONCLUSIONS: This network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.
BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is the most common cause of liver disease. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs. APPROACH AND RESULTS: Medline, EMBASE and CENTRAL were searched for randomised controlled trials evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, at least 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and at least 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis. Among 49 included trials, treatments modulating energy (Risk ratio (RR): 1.92, Credible intervals (Crl): 1.59-2.34) were most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.66, Crl: 0.65-4.50), bile acids (RR: 1.37, Crl: 0.99-1.92) and inflammation (RR: 1.00, Crl: 0.75-1.33). Energy and bile acids modulation were effective in at least 2-point NAS reduction without worsening of fibrosis (RR: 1.52, Crl 1.30-1.77; RR: 1.69, Crl 1.41-2.03) and at least 1-point reduction in fibrosis (RR: 1.26, Crl:1.05-1.49; RR: 1.54, Crl: 1.20-1.97). CONCLUSIONS: This network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.
Authors: Cheng Han Ng; Zhen Yu Wong; Nicholas W S Chew; Kai En Chan; Jieling Xiao; Nilofer Sayed; Wen Hui Lim; Darren Jun Hao Tan; Ryan Wai Keong Loke; Phoebe Wen Lin Tay; Jie Ning Yong; Gywneth Kong; Daniel Q Huang; Jiong-Wei Wang; Mark Chan; Mayank Dalakoti; Nobuharu Tamaki; Mazen Noureddin; Mohammad Shadab Siddiqui; Arun J Sanyal; Mark Muthiah Journal: Front Cardiovasc Med Date: 2022-08-08
Authors: Clarissa Elysia Fu; Cheng Han Ng; Nicholas W S Chew; Zane En Qi Heng; Yip Han Chin; Jingxuan Quek; Wen Hui Lim; Jieling Xiao; Kai En Chan; Darren Jun Hao Tan; Caitlyn Tan; Sitong Zhang; Teng Kiat Koh; Benjamin Nah; Yock Young Dan; Nicholas Syn; Mohammad Shadab Siddiqui; Arun J Sanyal; Mazen Noureddin; Mark Muthiah Journal: Front Med (Lausanne) Date: 2022-09-28