Meta-analysis of trials in non-alcoholic fatty liver disease with therapeutic interventions for metabolic syndrome

Abstract

Aims: Non-alcoholic fatty liver disease [NAFLD] is associated with metabolic syndrome [MS]. Current guidelines restrict therapy for NAFLD, other than weight loss, in early non-fibrotic disease. It was postulated that intervention with therapies for MS may improve liver fat content.

Methods: A systematic evaluation of Cochrane and PubMed databases was performed for NAFLD or NASH if they were: 1) interventions for metabolic syndrome or diabetes mellitus 2) randomized controlled trials [RCT], with 3) primary outcomes of liver fat content [LFC] (by magnetic resonance spectroscopy [MRS] or liver biopsy (Nonalcoholic Fatty Liver Disease Activity Score [NAS]).

Results: There were 30 RCT (in 24 publications) of 2409 subjects. LFC decreased with pioglitazone (MRS, -8.0 ± 1.0 %, p < 0.001), diet and exercise (-7.8 ± 1.7 %, p < 0.001) and omega-3 fatty acids (-6.0 ± 2.5 %, p = 0.02). Decreases in NAS scores were significant for pioglitazone (-1.4 ± 0.4 units, p < 0.001) and D&E (-1.0 ± 0.1 units, p < 0.001). Weight loss correlated with improvement in LFC (p < 0.001) and NAS (p < 0.001). Lowered serum triglycerides correlated with final LFC (p < 0.001) and NAS scores (p < 0.001).

Conclusions: Therapies of MS with weight loss, antiglycemic and triglyceride lowering medicines improved LFC and NAS scores. Further studies are necessary to demonstrate if these therapies would pre-emptively limit progression of disease.

Keywords: Meta-analysis; NAFLD; NASH; Non-alcoholic fatty liver disease; Steatohepatitis.