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Interferon L3 variant may increase risk for HCC after HCV therapy

Researchers suggest that interferon L3 rs12979860 may be a risk factor for the development of hepatocellular carcinoma among patients treated for hepatitis C virus infection, according to published data from a retrospective study.

Researchers analyzed data from 1,118 patients with HCV infection (median age; 60 years) treated with pegylated interferon and ribavirin from March 2000 to October 2009 at the Chang Gung Memorial Hospital in Kaohsiung, Taiwan. Of these patients, 589 were men and 71.64% achieved sustained virologic response.

Clinical and biochemical features were assessed every 3 to 6 months and patients underwent an ultrasound 24 weeks post-treatment, according to the research. All patient data was used in a Kaplan-Meier analysis to determine the risk for development of HCC and DNA were measured and analyzed for rs12979869 in IFNL3. The patients were followed up from the beginning of HCV therapy until March 2013 or up until HCC diagnosis or death.

Overall, 9.66% of patients developed HCC over the course of follow-up (n = 108). Analysis of IFNL3 rs12979860 showed that 86.4% of patients had the CC genotype (n = 967), 13.2% had the CT genotype (n = 148) and 0.3% had the TT genotype (n = 3). HCC was more common in patients with the IFNL3 rs12979860 CT and TT genotype compared with patients with the CC genotype (18.5% vs. 8.3%; P < .001).

Multivariate Cox regression analysis showed older age, low platelet count, an alpha-fetoprotein (AFP) level of at least 20 ng/mL, advanced stage fibrosis, diabetes, no SVR, and the IFNL3 rs12979860 CT and TT genotypes to be risk factors for HCC (P < .05).

The IFNL3 rs12979860 genotype did not have a great effect on risk for HCC among patients who achieved SVR. Older age, low platelet count, high AFP levels and advanced fibrosis were risk factors for HCC among patients who achieved SVR.

Among patients who did not achieve SVR, fibrosis stage (HR = 4.68; 95% CI, 2-10.91) and the IFNL3 rs12979860 CT and TT genotypes were independent risk factors for HCC (HR = 1.8; 95% CI, 1.06-3.07). Also, patients with HCV genotype 1 and diabetes had a higher incidence of HCC (P ≤ .005).

“The IFNL3 rs12979860 CT and TT polymorphisms are associated with a risk for HCC, especially in patients without an SVR,” the researchers concluded. “Screening for these polymorphisms may be useful for identifying some HCV patients at substantial risk of HCC after antiviral therapy.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.