title: Comparative efficacy of interventions on nonalcoholic fatty liver disease (NAFLD): A PRISMA-compliant systematic review and network meta-analysis.
abstract: BACKGROUND
  The prevalence of nonalcoholic fatty liver disease (NAFLD) has significantly increased over the last decades. Despite existence of several interventions, there remains unclear which interventions work the best.
  
  
  METHODS
  A systematic review and network meta-analysis of randomized trials comparing efficacy of all treatment options in NAFLD were performed to determine comparative efficacy and safety of interventions in the management of NAFLD. Several electronic databases were searched up to Nov 15, 2015. Outcomes include liver histological outcomes (i.e., fibrosis), all-cause mortality, cirrhosis, and safety. A network meta-analysis was applied to estimate pooled risk ratios (RR). Quality of evidence was assessed using GRADE criteria.
  
  
  RESULTS
  A total of 44 studies (n = 3802) were eligible. When compared with placebo, obeticholic acid (OCA) was the only intervention that significantly improved fibrosis with RR (95% CI) of 1.91 (1.15, 3.16), while pentoxyfylline (PTX) demonstrated improved fibrosis without statistical significance with RR (95% CI) of 2.27 (0.81, 6.36). Only thiazolidinedione (TZD) and vitamin E use resulted in significant increase in resolution of NASH, while OCA, TZD, and vitamin E significantly improved other outcomes including NAS, steatosis, ballooning, and inflammation outcomes. Quality of evidence varied from very low (i.e., metformin, PTX on mean change of ballooning grade) to high (OCA, TZD, vitamin E on improving histological outcomes). Limitations of this study were lack of relevant long-term outcomes (e.g., cirrhosis, death, safety), possible small study effect, and few head-to-head studies.
  
  
  CONCLUSIONS
  Our study suggests potential efficacy of OCA, TZD, and vitamin E in improving histologic endpoints in NAFLD. These findings are however based on a small number of studies. Additional studies are awaited to strengthen this network meta-analysis.
authors: Clinical Pharmacy Research Unit (CPRU), Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Mahasarakham, Thailand School of Pharmacy, Monash University Malaysia, Selangor, Malaysia Center of Pharmaceutical Outcomes Research, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok Center of Health Outcome Research and Therapeutic Safety, School of Pharmaceutical Sciences,University of Phayao, Phayao Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle School of Pharmacy, University of Wisconsin, Madison, WI School of Population Health, University of Queensland, Brisbane, QLD, Australia.
authors: Ratree
authors: R
authors: Sawangjit
authors: Bunchai
authors: B
authors: Chongmelaxme
authors: Pochamana
authors: P
authors: Phisalprapa
authors: Surasak
authors: S
authors: Saokaew
authors: Ammarin
authors: A
authors: Thakkinstian
authors: Kris V
authors: KV
authors: Kowdley
authors: Nathorn
authors: N
authors: Chaiyakunapruk
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D010431:Pentoxifylline / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D045162:Thiazolidinediones; C464660:obeticholic acid; D002635:Chenodeoxycholic Acid; D014810:Vitamin E; C089946:2,4-thiazolidinedione; D010431:Pentoxifylline