IFNL4 polymorphism predicts response to hepatitis C treatment after liver transplantation

• HCV-related cirrhosis is the main indication for liver transplantation worldwide.
• rs368234815 (IFNL4) is associated with antiviral therapy response after liver transplantation.
• After a liver transplant, the genetic backgrounds of donors and recipients coexist.
• Response to antiviral therapy increases when both recipients and donors carry favorable genotypes.
• IFNL4 polymorphism is an important predictor of HCV treatment response.

BackgroundRecent studies in chronic hepatitis C patients have shown that rs368234815 polymorphism nearby IL28B is a better predictor of response to antiviral treatment with pegylated interferon and ribavirin than IL28B polymorphisms (rs12979860 and rs8099917). Its effect could be related to interferon lambda 4 (IFNL4), a protein which seems to confer some paradoxical disadvantages in hepatitis C virus (HCV) immune response.ObjectivesTo assess the role of IFNL4 rs368234815 polymorphism on the response to antiviral treatment after liver transplantation (LT).Study designIFNL4 and IL28B polymorphisms were genotyped in 86 HCV-infected LT recipients and in their donors; all patients had undergone antiviral treatment with pegylated interferon and ribavirin after LT.ResultsIFNL4 polymorphism strongly correlated with IL28B ones (p < 0.001). The favorable IFNL4 genotype (TT/TT) was significantly more frequent among donors than recipients (60% donors vs. 22% recipients, p < 0.001). Recipient TT/TT genotype was associated with a higher sustained virological response rate after LT (p = 0.024). Nevertheless, the highest sustained virological response frequency was found when both donors and recipients had favorable genotypes (73% vs. 25%, p = 0.002), suggesting a role for donor genotype.ConclusionsOur study demonstrates that IFNL4 rs368234815 polymorphism is an important predictor of response to antiviral treatment in the LT setting. These findings warrant further studies on IFNL4 role in immune response against HCV.