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Updated: Mar 9, 2026

Author Spotlight: Advancements and Challenges in Hepatitis B Virus Detection
Published on: December 15, 2023
PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease
Habeeb Salameh1, Maen Masadeh1, Muhannad Al Hanayneh1
1Habeeb Salameh, Muhannad Al Hanayneh, Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX 77555, United States.
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 PubMed/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 hepatitis 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.
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