Association Of Serum Interferon-Lambda 3 Levels With Hepatocarcinogenesis In Chronic Hepatitis C Patients Treated With Direct-Acting Antiviral Agents

Aim Although the efficacy of hepatitis C virus (HCV) treatment is improved dramatically by direct-acting antiviral agents (DAAs), the assessment of hepatocellular carcinoma (HCC) remains important. Interferon lambda 3 (IFN-lambda 3) is associated with liver fibrosis and inflammation in chronic hepatitis C (CHC) patients, but its impact on carcinogenesis remains controversial and little is known about its effects after viral clearance. To determine the contribution of IFN-lambda 3 to hepatocarcinogenesis after HCV clearance, we analyzed IFNL3 genotypes and serial serum IFN-lambda 3 levels in CHC patients who achieved sustained virologic responses (SVR). Methods This study comprised 201 CHC patients treated with DAAs. Serum samples were collected sequentially and IFN-lambda 3 levels were quantified by chemiluminescence enzyme immunoassay. The IFNL3 polymorphism (rs8099917) was genotyped in 195 patients. Results One hundred and twenty-five patients were rs8099917 T/T and 70 were non-T/T. Serum IFN-lambda 3 levels did not differ significantly with IFNL3 genotype, dropped markedly by 1 week and remained low up to 24 weeks after the end of treatment. Interferon-lambda 3 levels were significantly higher after viral clearance in patients who developed HCC and were associated with a higher potential for hepatocarcinogenesis, such as a higher frequency of non-hypervascular hypointensive nodules (P = 0.046), higher stages of liver fibrosis (P < 0.001), and higher post-treatment levels of Wisteria floribunda agglutinin positive Mac-2 binding protein (P < 0.001) and alanine aminotransferase (P < 0.001). Conclusions Serum IFN-lambda 3 levels after HCV clearance are associated with the potential for HCC development. Interferon-lambda 3 could be helpful for elucidating the relationships among immunologic status, liver fibrosis, liver inflammation, and hepatocarcinogenesis, after achieving SVR.