Effectiveness of Omega-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome with the main characteristic of diffuse liver cells with fatty changes. The clinical evolution of NAFLD includes simple non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), liver fibrosis and cirrhosis, and even hepatocellular carcinoma. METHODS AND FINDINGS: We conducted this review to identify the effectiveness of omega-3 polyunsaturated fatty acids (ω-3 PUFA) in NAFLD. We searched PubMed, Cochrane Library and Embase. All randomized controlled trials (RCTs) of ω-3 PUFA treatment for NAFLD were considered. Two reviewers assessed the quality of each study and collected data independently. Disagreements were resolved by discussion among the reviewers and any of the other authors of the paper. We performed a meta-analysis and reported summary estimates of outcomes as inverse variance (IV), fixed or random, with 95% confidence intervals (CIs). We included seven RCTs involving 442 patients (227 for the experimental group and 215 for the control group). All the patients were divided into two groups: one treated with ω-3 PUFA and the other was the control group (generally placebo). The demographics of the ω-3 PUFA and control groups were comparable. Beneficial changes in alanine aminotransferase (ALT) (IV 95% CI: −7.61 [−12.83 to −2.39], p = 0.004), total cholesterol (TC) (IV 95% CI: −13.41 [−21.44 to −5.38], p = 0.001), triglyceride (TG) (IV 95% CI: −43.96 [−51.21 to −36.71], p<0.00001) and high-density lipoprotein cholesterol (HDL-C) (IV 95% CI: 6.97 [2.05 to 11.90], p = 0.006) favored ω-3 PUFA treatment. Omega-3 PUFA tended towards a beneficial effect on aspartate aminotransferase (AST) (IV 95% CI: −6.89 [−17.71 to 3.92], p = 0.21), γ-glutamyl transferase (GGT) (IV 95% CI: −8.28 [−18.38 to 1.83], p = 0.11) and low-density lipoprotein cholesterol (LDL-C) (IV 95% CI: −7.13 [−14.26 to 0.0], p = 0.05). CONCLUSIONS: Supplementation with ω-3 PUFA is a practical and effective treatment for NAFLD to decrease ALT, TC and increase HDL-C, especially to decrease TG. Omega-3 PUFA also has a tendency toward a beneficial effect on AST, GGT and LDL-C. More high-quality, large RCTs are needed to validate our findings.