Published online Apr 7, 2015. doi: 10.3748/wjg.v21.i13.3904
Peer-review started: September 19, 2014
First decision: November 5, 2014
Revised: November 29, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: April 7, 2015
Processing time: 203 Days and 6.9 Hours
AIM: To evaluate interferon-λ3 (IFNL3) polymorphisms in response-guided pegylated interferon-α plus ribavirin (Peg-IFNα/RBV) therapy for genotype 2 (G2) chronic hepatitis C.
METHODS: Between January 2006 and June 2012, a total of 180 patients with chronic infections of G2 hepatitis C virus (HCV) were treated with response-guided Peg-IFNα/RBV therapy. The treatment duration was 24 wk for patients who achieved rapid virologic response (RVR), and 36 or 48 wk for patients who did not. Then, the impact of the IFNL3 single nucleotide polymorphism genotype (TT/non-TT at rs8099917) on treatment outcomes was evaluated in the 180 patients, and between patients infected with either HCV sub-genotype 2a or 2b.
RESULTS: Of the 180 patients evaluated, 111 achieved RVR, while the remaining 69 patients did not. In RVR patients, the sustained virologic response (SVR) rate was 96.4%, and the IFNL3 genotype did not influence the SVR rate (96.6% vs 95.8% in IFNL3 genotype TT vs non-TT). However, in non-RVR patients, the SVR rate decreased to 72.5% (P < 0.0001), and this rate was significantly different between the IFNL3 genotype TT and non-TT groups (80.0% vs 42.9%, P = 0.0146). Multivariate regression analysis in non-RVR patients identified the IFNL3 genotype TT as the only baseline-significant factor associated with SVR (OR = 5.39, 95%CI: 1.29-22.62; P = 0.0189). In analysis according to HCV sub-genotype, no significant difference in the SVR rate was found between HCV sub-genotypes 2a and 2b.
CONCLUSION: In response-guided Peg-IFNα/RBV combination therapy for chronically HCV G2-infected patients, the impact of the IFNL3 genotype on SVR was limited to non-RVR patients.
Core tip: Interferon-λ3 (IFNL3) single nucleotide polymorphisms (SNPs), such as rs8099917 and rs12979860, affect the virologic responses of chronically hepatitis C virus genotype 1-infected patients to response-guided pegylated interferon-α plus ribavirin therapy. However, the significance of these SNPs in therapy for hepatitis C virus genotype 2 (G2)-infected patients is unclear. We show that rs8099917 significantly influences sustained virologic response (SVR) achievement only in patients who do not attain rapid virologic response. Therefore, IFNL3 SNP genotyping is valuable for predicting SVR only in non-rapid virologic response patients, irrespective of the G2 subtype, even when therapy is extended up to 48 wk.