Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection

Abstract

BackgroundPatients infected with hepatitis C virus (HCV) genotype 1 respond poorly to standard treatment with 50% or less achieving sustained virologic response. Predicting outcome is essential and could help avoid unnecessary treatment and reduce health cost. Recently, an association of amino acid substitutions in the core region and treatment outcome was observed in Japanese patients. In the present study, the impact of these mutations on response kinetics and treatment outcome was explored in Caucasian patients.MethodsThe core region of HCV pre-treatment samples obtained from 50 patients treated with peginterferon/ribavirin in a previous Swedish clinical trial with genotype 1 infection were sequenced. The alleles at rs12979860, a single nucleotide polymorphism (SNP), were assessed in order to identify any co-association with this strong response predictor.ResultsNo association between treatment response and substitutions of core residue 91 was found. In contrast, substitutions of core residue 70 were observed in 6/21 (29%) non-responders, but only in one of 29 responders (p = 0.03), and were more common in subgenotype 1b (R70Q in 6 of 13 strains) than in 1a (R70P in 1 of 37 strains, p = 0.004). The rs12979860 SNP upstream of the IL28B gene was overall the strongest response predictor (p = 0.0001). Core 70 substitutions were associated with poorer response kinetics in patients carrying the CT genotype at rs12979860.ConclusionsThe results indicate that substitutions of core residue 70 are related to treatment response in Caucasian patients with HCV-1b infection, but are of less importance than IL28B polymorphism.

Hepatitis C virus Genotype 1a core gene nucleotide patterns associated with hepatocellular carcinoma risk

“…A general trend for increased variability in HCV core gene sequence in HCC tissues and during progression to more advanced liver disease has also been noted previously (Horie et al, 1999;Khaliq et al, 2011). Several investigations have demonstrated differences in HCV core gene sequences between tumour and nontumour tissue in the same liver (De Mitri et al, 1998;Horie et al, 1999;Delhem et al, 2001;Rüster et al, 2001;Alam et al, 2002;Ogata et al, 2002;Alestig et al, 2011).…”

Interleukin 28B rs12979860 CT, rs12980275 GA, rs8099917 GT and TT genotypes are the Predictors of Rapid Viral Response in Hepatitis C Virus-Infected Patients

“…Its effect has been shown in HCV+HIV co-infected patients as well (25,26). This CC genotype was also reported to be associated with a higher rate of spontaneous clearance in European and Asian populations (20,27). On the other hand, these significant SNPs observed in Europe and Asia were not strongly associated with Japanese population (17).…”

“…SNPs of the IL28B gene has been extensively described in the literature but allele frequencies, in particular rs809917, differs somewhat between world-wide populations (17,18,19,20). Therefore, the predictive power of SNPs may vary between different cohorts.…”

Different impact of IL28B polymorphisms on response to peginterferon-α plus ribavirin in HIV-positive patients infected with HCV subtypes 1a or 1b

“…3,4 In less extent, substitutions at viral core and NS5A residues may also influence treatment outcomes. 23,24 The information available suggest that all these variables will remain as predictors of response to new direct antiviral agents against HCV, 5-8 most likely because these drugs will initially be given as third agent along with pegIFN/RBV.…”