PNPLA3 rs738409 Polymorphism Associated with Hepatic Steatosis and Advanced Fibrosis in Patients with Chronic Hepatitis C Virus: A Meta-Analysis

Abstract

Background/aims: The recognition of a correlation between patatin-like phospholipase domain containing-protein 3 (PNPLA3) rs738409 (C>G) and the severity of liver steatosis or fibrosis in chronic hepatitis C (CHC) has not reached a consensus. This meta-analysis sought to investigate with accuracy the association between the PNPLA3 rs738409 (C>G) polymorphism and liver steatosis and advanced fibrosis in CHC patients.

Methods: We performed a comprehensive literature search from the PubMed, Embase, Web of Science, and Google Scholar databases up to December 31, 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 the severity of liver fibrosis was significantly higher in CHC patients with PNPLA3 rs738409 GG in Caucasians (versus CC+CG OR, 2.29; 95% CI, 1.57 to 3.35; p<0.05) but not Asian populations. In Caucasians, liver steatosis was also more severe in CHC patients with rs738409 GG (versus CC+CG; OR, 4.33; 95% CI, 2.59 to 7.22; p<0.05). The sensitivity analysis indicated 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.

Keywords: Advanced liver fibrosis; Fatty liver; Hepatitis C, chronic; Meta-analysis; Patatin-like phospholipase domain containing protein 3 rs738409.

Fig. 1

Schematic of the study selection process. HCV, hepatitis C virus.

Fig. 2

Advanced fibrosis. Summary estimates for odds ratios (ORs, effect), the corresponding 95% confidence interval (CI) limits (lower and upper), percent weight, and overall or subtotal (I² and p-value) were calculated by fixed effects meta-analysis for advanced fibrosis. The first author of the study and the year of publication are shown. (A) The forest plots of all five studies were relevant to advanced fibrosis and the subgroup analysis by ethnicity. (B) The forest plots of all five studies were relevant to advanced fibrosis and the subgroup analysis based on hepatitis C virus (HCV) genotype.

Fig. 3

Liver steatosis. Summary estimates for odds ratios (ORs, effect), the corresponding 95% confidence interval (CI) limits (lower and upper), percent weight, and overall or subtotal (I² and p-value) were calculated by fixed effects meta-analysis for liver steatosis. The forest plots of all five studies were relevant to liver steatosis and the subgroup analysis based on hepatitis C virus (HCV) genotype.

Fig. 4

Sensitivity analysis of the summary odds ratio. The results were computed by omitting each study in turn. Meta-analysis random effects estimates (exponential form) were used. The two ends of the dotted lines represent the 95% confidence interval. (A) Association between patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 single nucleotide polymorphism (SNP) and advanced fibrosis. (B) Association between PNPLA3 rs738409 SNP and liver steatosis.

Fig. 5

Begger’s funnel plot. Each point represents a separate study for the indicated association. Horizontal line means magnitude of the effect. (A) Association between patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 single nucleotide polymorphisms (SNP) and advanced fibrosis. (B) Association between PNPLA3 rs738409 SNP and liver steatosis. s.e., standard error; LogOR, natural logarithm of odds ratio.