PNPLA3 Rs738409 Polymorphism Associated With Hepatic Steatosis And Advanced Fibrosis In Patients With Chronic HCV:A Meta-analysis

Background : Nearly 3% of the worldwide population has been infected with the hepatitis C virus(HCV) and about 80% of these cases are chronic.1,2 Chronic HCV(CHC) infection has become one of the leading causes of liver-related mortality. Several potential genetic risk factors have been identified as having a key role in the severity of CHC-associated liver disease. The best documented is the polymorphism rs738409(C>G) of patatin-like phospholipase domain-containing protein 3(PNPLA3).However, the recognition of a correlation between PNPLA3 rs73409(C>G)and the severity of liver steatosis or fibrosis in CHC has not reached a consensus.Objective: This meta-analysis sought to investigate with accuracy the association between the PNPLA3 rs738409(C>G) polymorphism and liver steatosis and advanced fibrosis in chronic hepatitis C(CHC) patients.Methods: We performed a comprehensive literature search from the Pub Med, Embase, Web of Science, and Google Scholar databases conducted up to 31 December 2014. Crude odds ratios(ORs) with 95%confidence intervals(CIs) were calculated. Statistical analyses were performed using STATA 12.0 software.Results: The meta-analysis revealed that the severity of liver fibrosis was significantly higher in CHC patients with PNPLA3 rs738409 GG, in Caucasian(cf. CC+CG, OR, 2.29; 95% CI: 1.57-3.35; P < 0.05) but not Asian populations. In Caucasians, liver steatosis was also more severe in CHC patients with rs738409 GG(cf. CC+CG, OR, 4.33; 95% CI: 2.59-7.22;P <0.05). The sensitivity analysis indicated that the results of this meta-analysis were stable and no publication bias was detected.Conclusions: PNPLA3 rs738409(C>G) was associated with the risk of both advanced liver fibrosis and steatosis in patients with CHC,especially among Caucasian populations.