Effects of Polymorphisms in Interferon λ 3 (Interleukin 28B) on Sustained Virologic Response to Therapy in Patients With Chronic Hepatitis D Virus Infection

BACKGROUND & AIMS: We investigated the association between interferon lambda 3 (IFNL3) genotype (also known as interleukin 28B) and response to IFN alpha therapy in patients with chronic hepatitis D virus (HDV) infection. METHODS: We studied IFNL3 genotypes of 32 patients (19 men; median age, 42.5 y) with chronic HDV infection. Nineteen patients (59%) were treated with pegylated IFN alpha and 13 patients (41%) were treated with standard IFN alpha, for at least 12 months. Levels of HDV RNA were measured before the initiation of treatment and every 6 months thereafter; patients were followed up for a median time of 16 months (range, 6-164 mo) after treatment ended. We used real-time polymerase chain reaction to classify the IFNL3 polymorphism rs12979860 as CC, CT, or TT, and rs8099917 as TT, GT, or GG. A virologic response was defined as undetectable HDV RNA in serum, and a sustained virologic response (SVR) was defined as undetectable HDV RNA after cessation of treatment until the end of the follow-up period. We evaluated the association between IFNL3 polymorphism and treatment response using univariate and multivariate analyses. RESULTS: After treatment, a response was achieved in 16 patients (50%) and an SVR was achieved in 9 (28%). The percentages of patients with CC, CT, and TT at rs12979860 were 47%, 47%, and 6%, respectively; the percentages of patients with TT, GT, and GG at rs8099917 were 69%, 28%, and 3%, respectively. Rates of SVR were 27%, 27%, and 50% in patients with CC, CT, TT at rs12979860 (P=.78 for CC vs CT vs TT) and 36%, 11%, and 0% in patients with TT, GT, and GG at rs8099917 (P=.30 for TT vs GT vs GG). CONCLUSIONS: The IFNL3 polymorphisms rs12979860 and rs8099917 do not significantly affect responses of patients with chronic HDV infection to treatment with IFN alpha.