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Pharmacological interventions for non-alcoholic fatty liver disease: a systematic review and network meta-analysis
  1. Kannan Sridharan1,
  2. Gowri Sivaramakrishnan2,
  3. Reginald Paul Sequeira1,
  4. Abdelaziz Elamin3
  1. 1 Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
  2. 2 School of Oral Health, College of Medicine, Nursing and Health Sciences, Fiji National University, Suva, Fiji
  3. 3 Department of Pediatrics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
  1. Correspondence to Dr Kannan Sridharan, Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain; skannandr{at}


Aim Several drugs have been used for treating non-alcoholic fatty liver disease (NAFLD). The present study is a network meta-analysis of such drugs.

Design, setting and patients Randomised clinical trials comparing drug interventions in patients with NAFLD were analysed. OR and weighted mean difference (95 % CI) were the effect estimates for categorical and numerical outcomes, respectively. Random-effects model was used to generate pooled estimates. Surface under the cumulative ranking curve was used to rank the treatments.

Main outcome measures Proportion of responders was the primary outcome measure and non-alcoholic steatohepatitis scores, liver enzymes, lipid profile, body mass index, homeostatic model assessment of insulin resistance, intrahepatic fat and adverse events were the key secondary outcomes.

Results 116 studies were included in the systematic review and 106 in the meta-analysis. Elafibranor, gemfibrozil, metadoxine, obeticholic acid, pentoxifylline, pioglitazone, probiotics, telmisartan, vildagliptin and vitamin E significantly increased the response rate than standard of care. Various other drugs were observed to modify the secondary outcomes favourably. Probiotics was found with a better response in children; and elafibranor, obeticholic acid, pentoxifylline and pioglitazone in patients with type 2 diabetes mellitus. The quality of evidence observed was either low or very low.

Conclusion In patients with NAFLD, several drugs have been shown to have variable therapeutic benefit. However, the estimates and the inferences should be considered with extreme caution as it might change with the advent of future head-to-head clinical trials.

  • clinical pharmacology
  • Lipid disorders
  • gastroenterology

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  • Contributors KS had full access to all of the data in the study. KS takes responsibility for the integrity of the data, the accuracy of the data analysis and the final decision to submit for publication. Study concept and design: KS, GS; acquisition, analysis or interpretation of data: KS, GS, RPS, AE; drafting of the manuscript: KS, GS, RPS, AE; critical revision of the manuscript for important intellectual content: KS, GS, RPS, AE; statistical analysis: KS, GS.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.