ABSTRACT To update the information on genetic markers influencing the outcome of hepatitis C virus (HCV) infection.
Single-nucleotide polymorphisms (SNPs) in the region of the IL28B gene on chromosome 19, coding for the interferon (IFN)-λ3, are involved in HCV spontaneous and treatment-induced clearance, and may have an influence on liver fibrosis and inflammation in chronic carriers. The rs12979860 SNP has been recommended as single diagnostic genotype. IL28B variations are strongly associated with response to pegylated-IFN plus ribavirin (Peg-IFN/RBV) in patients with chronic infection by HCV genotype 1 or 4. Thus, the rs12979860 CC genotype is associated with a two-fold increase in the sustained virological response (SVR) rate in this setting. SVR is less influenced by IL28B variants in HCV genotype 2 or 3 carriers. The rs12979860 CC genotype frequencies vary among diverse genetic ancestor groups, explaining partly the differences in SVR among them. The underlying mechanisms are unclear, but it may involve the expression of IFN-stimulated genes in the liver. Inosine triphosphatase genotype is predictive of RBV-induced anemia, but its clinical usefulness is less straightforward than that of IL28B SNPs.
IL28B genotyping can aid in Peg-IFN/RBV clinical decision-making, and it may be useful in the selection of candidates for triple therapy with Peg-IFN/RBV plus direct-acting antiviral drugs.
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ABSTRACT: To optimize standard treatment of chronic hepatitis C in responder patients who have achieved undetectable viral load, a prospective study was conducted to determine the factors and kinetics of virologic relapse. Responder patients were monitored 2, 4, 8, 12, 16, and 24 weeks after the end of treatment with pegylated interferon and ribavirin. Forty-seven of the 154 patients (30.5%) relapsed. Relapse was significantly associated with absence of rapid virologic response (RVR), retreatment, higher baseline viral load, older age, and lower weight-based dose of pegylated interferon. Relapse was more frequent in patients failing to achieve a RVR after receiving pegylated interferon alpha 2a < 2.5 µg/week or alpha 2b < 1.5 µg/week (P = 0.002). Among patients infected with hepatitis C virus (HCV) genotype 1 with non-CC IL-28B polymorphism (rs12979860), viral decay during treatment was lower in relapsers (P = 0.003 at week 4). Relapse was detected at weeks 2, 4, 8, and 12 after the end of treatment for 5, 8, 10, and 6 patients infected with HCV genotype 1, respectively. Positive predictive values for sustained virologic response were 70.9%, 80.2%, 91.9%, and 98.8% at weeks 2, 4, 8, and 12, respectively. Only one patient relapsed beyond 24 weeks. Closer follow-up and treatment adaptation in patients failing to achieve RVR may decrease the relapse rate in slower responders and heavier patients. Monitoring viral load as early as 1 month after the end of treatment could be useful to assess virologic response. J. Med. Virol. 85:1191-1198, 2013. © 2013 Wiley Periodicals, Inc.Journal of Medical Virology 07/2013; 85(7):1191-8. · 2.37 Impact Factor
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ABSTRACT: Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia. Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2-CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5. Compared to IDUs seronegative for both HCV and HIV (HCV-/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+were 92% and 82%, respectively, less likely to possess the CCR5-HHG*1 haplotype, after controlling for co-variates (Padjusted = 1.89×10(-4) and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG*1 haplotype pairs. Approximately 25% and<10% of HCV-/HIV- IDUs and HCV-/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype. Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs.PLoS ONE 01/2013; 8(7):e70561. · 3.73 Impact Factor