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HCV and CXCL1 polymorphism may predict cirrhosis

The presence of the CXCL1 rs4074 A allele can be a genetic risk factor for cirrhosis among patients with hepatitis C genotype 1, according to recent results.

The study included 237 white patients with chronic hepatitis C genotype 1 infection, including 75 with and 162 without cirrhosis, along with a control group of 342 participants. Researchers established the presence of the CXCL1 rs4074 polymorphism and then monitored serum levels and induction as a response to HCV proteins, in order to determine whether the polymorphism is a risk factor for the development of cirrhosis.

The distribution of CXCL1 genotypes was 29.3% GG, 54.7% GA and 16.0% AA among patients with cirrhosis; 45.1% GG, 44.4% GA and 10.5% AA among patients without cirrhosis, and 46.2% GG, 40.9% GA and 12.9% AA among the control group. Researchers found that rs4074 A allele carriers were more common among patients with cirrhosis and HCV (70.7%) than among patients with HCV alone (54.9%, OR=1.98, 95% CI, 1.10-3.55) and among individuals in the control group (55.0%, OR=2.07, 95% CI, 1.21-3.55). Patients with HCV and cirrhosis also had a higher frequency of the A allele than those without cirrhosis (43.3% vs. 32.7%, OR=1.529, P=.02) and the control group (43.3% vs. 33.3%, OR=1.529, P=.02).

CXCL1 serum levels were significantly higher among patients with both HCV and the A allele (GA=177.3±15.6 pg/mL and AA=359.1±104.7 pg/mL) compared to controls (GA=133.7±10.5 pg/mL and AA=152.4±13.4 pg/mL; P=.034 for GA and P=.025 for AA). Patients with HCV and the GG genotype did not have significantly different serum levels than those with the same genotype in the control group.

Results of a multivariate regression analysis suggested that A allele carrier status was an independent risk factor for cirrhosis (OR=2.065; 95% CI, 1.114-3.821), along with age. Investigators also found that A allele carriers were more prone to advanced liver fibrosis than patients with the GG genotype (P=.067).

“Our studies on the CXCL1 rs4074 polymorphism have provided first insights into how genetic variants of chemokines and their receptors that are involved in the regulation of fibrogenesis might differentially affect progression of chronic viral hepatitis to cirrhosis,” the researchers wrote. “This should stimulate further studies to clarify the role of such polymorphisms in the pathogenesis of fibrosis and progression toward cirrhosis.”