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Polymorphisms increased risk for steatosis in patients with HCV genotype 1

Phospholipase domain containing 3, or PNPLA3, polymorphism was a predictor for steatosis among Spanish patients with hepatitis C virus genotype 1 infection, according to study data.

Researchers from various medical centers in Spain sought to determine the relationship between PNPLA3 and steatosis and fibrosis after therapy with pegylated interferon plus ribavirin among a cohort of patients with HCV. 

“Liver steatosis is frequent among patients with chronic hepatitis C virus; its prevalence is higher than general population and individuals with other chronic liver diseases,” the researchers wrote.

The patients (n=474) were dosed with 180 mcg PEG-INF alfa-2a per week or 1.5 mcg/kg PEG-INF a-2b per week with 1,000 mg or 1,200 mg ribavirin per day for 24 or 48 weeks. Approximately 68% of patients had HCV genotype 1, 2.5% had genotype 2, 19.4% had genotype 3 and 9.3% had genotype 4. PNPLA3 and interleukin 28B polymorphisms also were genotyped; 50.8% of the patients had PNPLA3-CC (allele-G, 49.2% vs. non-allele-G, 50.8%) and 62.2% had IL-28B-CT/TT genotype.

Overall, steatosis was detected in 54.1% of patients with PNPLA3 allele-G and 39% in non-allele-G patients (P=.0001). More HCV genotype 1 patients had steatosis as a result of PNPLA3 allele-G compared with HCV genotype 1 patients with non-allele-G (50.6% vs. 32.3%; P=.001). PNPLA3 allele-G was associated with steatosis among all HCV patients, except genotype 3 (52.4% vs. 33%).

PNPLA3 allele-G, age and HCV genotype 3 were among those found to be independently associated with steatosis by multivariate analysis. PNPLA3 allele-G was found to be predictor of steatosis in patients with HCV genotype 1. PNPLA3 did not affect patients’ ability to achieve a sustained virologic response with therapy (117/233 reached SVR) or fibrosis severity.

“PNPLA3 rs738409 allele-G is shown as a crucial predictive factor of liver steatosis in HCV-genotype 1, but did not in genotype 3,” the researchers wrote. “These data demonstrate that PNPLA3 rs738409 allele-G generates metabolic steatosis, while steatosis in HCV-genotype 3 could be promoted by direct viral effect.”

Disclosure: The researchers report no relevant financial disclosures.