Interleukin‐28b CC genotype predicts early treatment response and CT/TT genotypes predicts non‐response in patients infected with HCV genotype 3

Abstract

Response to antiviral therapy for hepatitis C virus (HCV) depends upon the genotype and host immune response. IL28b gene mutations have been shown to modulate host antiviral immune response against genotype 1. However, the predictive value of IL28b polymorphism in genotype 3 HCV patients is largely unknown. The association of IL28b polymorphism with virological response was studied in 356 patients with genotype 3 chronic HCV undergoing treatment with peg-interferon and ribavirin and was compared with matched controls. IL28b genotyping followed by DNA sequencing was performed to identify the CC, CT, or TT genotypes. Two log reduction of HCV RNA at Day 7 (Quick Viral Response, QVR) and HCV RNA negativity at Day 28 (Rapid Viral Response, RVR) were analyzed with CC and non-CC genotypes in addition to other predictors of response. The associations of alleles with the response patterns were predicted. Sustained viral response was seen in 250 (70.2%) patients and the IL28b genotype CC/CT/TT distribution was 61.1%; 30.5%; and 8.4%, respectively. The non-CC genotypes were significantly higher in non-responders when compared to responders (67.6% vs. 38.9%, P < 0.001). Interestingly, the rapid viral response in responders was observed in 72.7% with the CC genotype and in 27.2% with the non-CC genotype (P < 0.001). Multivariate analysis showed CC genotype as an independent factor predicting the sustained viral response in patients infected with HCV genotype 3. In conclusion, the IL28b CT/TT genotype strongly correlates with treatment non-response in patients infected with HCV genotype 3 and CC genotype of IL28b is associated with higher quick viral response.

Hepatitis C virus and interferon type III (interferon-λ3/interleukin-28B and interferon-λ4): genetic basis of susceptibility to infection and response to antiviral treatment

“…The scenario is different if one considers GT3 HCV separately or uses an adequate sample size. In fact, it has been recently reported from the largest studies that the rs12979860 CC genotype is an independent predictive factor for an SVR also in GT3 HCV patients, whereas no association with an SVR in GT2 HCV infection was observed [40,41]. These data clearly suggest the relevance of sample size in determining the correlation between IL-28B genotype and RVR/SVR, and suggest a rationale for testing IL-28B genotyping also in patients with GT3 HCV.…”

Relation of IL28B Rs12979860 Polymorphism on Depression Symptoms in the Treatment of Chronic Hepatitis C

“…A number of studies have postulated that T-allele of rs12979860 was associated with worst SVR in CHC patients during the IFN treatment, although the mechanisms that da Cunha ECM et al . IL28B and Depression Symptoms in HCV regulate the IL28B genotypes on the success rate of therapy remain unclear [9,19,20,21,22] . In fact, this SNP had been claimed as the key predictor among IL28B SNPs for SVR in HCV infected patients [19] .…”

24 versus 48 Weeks of Peginterferon Plus Ribavirin in Hepatitis C Virus Genotype 6 Chronically Infected Patients with a Rapid Virological Response: A Non-Inferiority Randomized Controlled Trial

“…IL-28B polymorphisms are associated with SVR and RVR to PEG-IFN/RBV treatment in HCV-1 [ 41 – 44 ] and HCV-2/3 [ 45 , 46 ]. However, IL-28B genomic-based treatment paradigms for chronic hepatitis C infection need to be demonstrated in clinical trials.…”