Pharmacogenomic perspectives of chronic hepatitis C virus (HCV) infection

Tang, Jianming; Kaslow, Richard A.

doi:10.1038/sj.tpj.6500246

Cited by 8 publications

(7 citation statements)

References 17 publications

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“…Apart from environmental and viral factors, genetic variations are probably involved in the efficacy of interferon-based therapies for chronic hepatitis C. 21 Interferon-k induces antiviral, antiproliferative, and immune responses. 22 It has been mentioned in the context of HCV infection (i.e., suppression of its replication in vitro) 23,24 and has been applied in clinical HCV treatment.…”

Section: Discussionmentioning

confidence: 99%

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

et al. 2011

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Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r 2 5 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P 5 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) 5 4.27, 95% confidence interval (CI) 5 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR 5 0.28, 95% CI 5 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR 5 3.10, 95% CI 5 1.34-7.21, P 5 0.008), and the pretreatment level of aspartate aminotransferase (OR 5 0.996, 95% CI 5 0.99-1.00, P 5 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI 5 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. (HEPATOLOGY 2011;53:7-13)

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Section: Discussionmentioning

confidence: 99%

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

et al. 2011

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“…Asians were more likely to respond to treatment, whereas Hispanics and African Americans were less likely, as compared with Caucasians [Muir, 2004;Hepburn, 2004]. The higher responsive rate in European Americans than African Americans may reflect the genetic backgrounds [Tang and Kaslow, 2004].…”

Section: General Host Factorsmentioning

confidence: 95%

“…Host factors that may affect drug response include age, gender, race, HLA alleles and host immune responses [Bruno, 2004;Gao, 2004]. In addition, the influence of human genome variation on treatment response has also been reported [Tang and Kaslow, 2004]. Recently, use of gene expression patterns of liver biopsy for predicting treatment responsiveness in CHC has been reported [Chen, 2005].…”

Section: Introductionmentioning

confidence: 97%

Prospect of Individualized Medicine in Chronic Hepatitis C Therapy by Pharmacogenomics

Hwang¹,

Su²,

Chen

et al. 2006

CPG

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Interferon-and ribavirin combination therapy has been the current choice for treating chronic hepatitis C (CHC) patients. The treatment takes 6 to 12 months but the overall sustained response rate is only around 50% and often brings significant adverse effects to some patients. The treatment outcome has been shown to be associated with various viral factors, such as viral loads before and during treatment and, most importantly, viral genotypes and quasispecies. Host factors that may affect drug response include age, gender, ethnicity, HLA alleles and stage of liver fibrosis. Recent studies have further indicated an association between patients' genotypes and their treatment efficacy.In this review article, we evaluate and summarize factors that may contribute to the treatment outcome of CHC. The content is divided into four categories: 1. viral factors: viral load, viral genotype and early viral response; 2. general host factors: gender, age, treatment period/dosage and kinds of IFN; 3. host genetic polymorphisms, particularly single nucleotide polymorphism (SNP) association studies; and 4. gene expression profiles in hepatitis C liver tissues.In summary, recent advances in pharmacogenomics have demonstrated the potential applications of genetic polymorphisms and expression patterns in determining treatment responsiveness in chronic hepatitis C. By combining both human and viral genotypes and their expression, it becomes plausible to satisfactorily assess the clinical outcomes prior to interferon combination treatment for CHC patients.

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“…Host genetic variations are probably involved in the efficacy of IFN-based therapies for CHC [81]. Genetic polymorphisms of human leukocyte antigen, CC chemokine receptor 5, cytotoxic T lymphocyte antigen-4, interleukin-10, low molecular mass polypeptide 7, MxA, and transforming growth factor- β 1 have been reported to have significant associations with responsiveness [82–89].…”

Section: Factors Associated With Treatment Efficacymentioning

confidence: 99%

Evolution of Interferon-Based Therapy for Chronic Hepatitis C

Chen

2010

Hepatitis Research and Treatment

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Since 1986, interferon-alfa (IFN-α) monotherapy has been administered for patients with chronic hepatitis C (CHC). However, sustained response rate is only about 8% to 9%. Subsequent introduction of ribavirin in combination with IFN-α was a major breakthrough in the treatment of CHC. Sustained virological responses (SVRs) rate is about 30% in hepatitis C virus genotype 1 (HCV-1) patients, and is about 65% in HCV-2 or -3 patients. After 2000, pegylated interferon (PegIFN) much improved the rates of SVR. Presently, PegIFN-α-ribavirin combination therapy has been current standard of care for patients infected with HCV. In patients with HCV-1, treatment for 48 weeks is optimal, but 24 weeks of treatment is sufficient in HCV-2 or -3 infected patients. Clinical factors have been identified as predictors for the efficacy of the IFN-based therapy. The baseline factor most strongly predictive of an SVR is the presence of HCV-2 or -3 infections. Rapid virological response (RVR) is the single best predictor of an SVR to PegIFN-ribavirin therapy. If patients can't achieve a RVR but achieve a complete early virological response (cEVR), treatment with current standard of care can provide more than 90% SVR rate. HCV-1 patients who do not achieve an EVR should discontinue the therapy. Recent advances of protease inhibitor may contribute the development of a novel triple combination therapy.

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Pharmacogenomic perspectives of chronic hepatitis C virus (HCV) infection

Cited by 8 publications

References 17 publications

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

Prospect of Individualized Medicine in Chronic Hepatitis C Therapy by Pharmacogenomics

Evolution of Interferon-Based Therapy for Chronic Hepatitis C

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