PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease

AIM To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS Literature was searched systematically from Pub Med/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C(CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum(fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms.RESULTS Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic he-patitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214(95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762(95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002(95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750(95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613(95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.

PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum

Background and Aims:Patatin-like phospholipase domain protein 3 (PNPLA3) polymorphisms (rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD).We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease.Methods:Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver,steatohepatitis,cirrhosis,and hepatocellular carcinoma) and NAFLD were included.Pooled data are reported as odds ratios (ORs) with 95% confidence intervals.Results:Of 393 potentially relevant studies,35 on NAFLD were included in the analysis.Compared to healthy controls,the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL)were 1.46 (1.16-1.85) and 2.76 (2.30-3.13),and were 1.75 (1.24-2.46) and 4.44 (2.92-6.76) among patients with non-alcoholic steatohepatitis respectively.The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90-6.13) and 5.05 (1.47-17.29) when comparing nonalcoholic hepatocellular carcinoma to NAFL patients.Among the NAFLD patients,the ORs for G allele frequency when comparing steatosis grade 2-3 to grade 0-1 NAFL,when comparing the NAFLD activity score of ≥ 4 to score ≤ 3,when comparing NASH to NAFLD,when comparing the presence of lobular inflammation to absence,and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43-3.80),1.80 (1.36-2.37),1.66 (1.42-1.94),1.58 (1.19-2.10),and 2.63 (1.87-3.69) respectively.Subgroup analysis based on ethnicity showed similar results.Conclusions:PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs.PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD.