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

Vispo, Eugenia; Rallón, Norma; Labarga, Pablo; Barreiro, Pablo; Benito, José M.; Soriano, Vincent

doi:10.1016/j.jcv.2012.05.012

Cited by 11 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This might be one of the reasons why resistance mutation was selected more frequently in HCV subgenotype 1a than in HCV subgenotype 1b in the case of telaprevir use [20], although in the ELECTRON study of NS5B inhibitor sofosbuvir, no differential resistance was observed between genotypes 1a and 1b despite 89% of the subjects being the HCV genotype 1a population [21]. Of interest, it has been reported that there are different impacts of IL28B variants on the treatment response to SOC between HCV subgenotype 1a and 1b strains together with HIV co-infection [22]. It will be important to determine HCV subgenotype 1a or 1b before commencing treatment for HCV genotype 1.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Hepatitis C Virus Subgenotypes 1a and 1b in Japanese Patients: Ultra-Deep Sequencing Analysis of HCV NS5B Genotype-Specific Region

Nakamoto

Jiang

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

BackgroundHepatitis C virus (HCV) subgenotypes 1a and 1b have different impacts on the treatment response to peginterferon plus ribavirin with direct-acting antivirals (DAAs) against patients infected with HCV genotype 1, as the emergence rates of resistance mutations are different between these two subgenotypes. In Japan, almost all of HCV genotype 1 belongs to subgenotype 1b.Methods and FindingsTo determine HCV subgenotype 1a or 1b in Japanese patients infected with HCV genotype 1, real-time PCR-based method and Sanger method were used for the HCV NS5B region. HCV subgenotypes were determined in 90% by real-time PCR-based method. We also analyzed the specific probe regions for HCV subgenotypes 1a and 1b using ultra-deep sequencing, and uncovered mutations that could not be revealed using direct-sequencing by Sanger method. We estimated the prevalence of HCV subgenotype 1a as 1.2-2.5% of HCV genotype 1 patients in Japan.ConclusionsAlthough real-time PCR-based HCV subgenotyping method seems fair for differentiating HCV subgenotypes 1a and 1b, it may not be sufficient for clinical practice. Ultra-deep sequencing is useful for revealing the resistant strain(s) of HCV before DAA treatment as well as mixed infection with different genotypes or subgenotypes of HCV.

show abstract

Section: Discussionmentioning

confidence: 99%

Prevalence of Hepatitis C Virus Subgenotypes 1a and 1b in Japanese Patients: Ultra-Deep Sequencing Analysis of HCV NS5B Genotype-Specific Region

Nakamoto

Jiang

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Vispo et al . [41] found evidence that IL28B genotype predicted clearance of HCV genotype 1a, but not 1b, in HIV/HCV co-infection. Dayyeh et al .…”

Section: Prediction Of Response To Pegifn/r Therapymentioning

confidence: 99%

Pharmacogenomics of hepatitis C infections: personalizing therapy

2012

View full text Add to dashboard Cite

It is a widely held view that drug response genes have not proved as useful in clinical practice as anticipated at the start of the genomic era. An exception is in the treatment for chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon α and ribavirin. In 2009, four independent genome-wide analyses identified IL28B polymorphisms that predict drug response in chronic hepatitis C (CHC). This discovery had immediate clinical impact. First, the IL28B genotype could be used to personalize therapy. In the 2 years since discovery, most of the more than 100,000 CHC patients commencing therapy for CHC in the West will have considered IL28B genotype testing. Second, the discovery has supported clinical trials for the use of the protein encoded by the gene known as interferon lambda. Third, it is expected that new insights into HCV pathogenesis will follow from studies of how IL28B affects HCV viral clearance and, ultimately, this will lead to new therapeutic strategies for CHC. This review discusses how IL28B genotyping is now used in personalizing therapy and, with the dramatically changing clinical landscape in CHC, with the advent of direct-acting antivirals, the prospects ahead.

show abstract

“…In patients with HCV genotype 4, an association has been found between the rs12979860 genotype and the overall rate of SVR 12. Thus, the impact of IL‐28B on SVR is not uniform among the HCV genotypes because it has the greatest impact on patients who are least likely to achieve SVR with peginterferon and ribavirin treatment, that is, patients with genotype 1 (likely 1a > 1b), who are closely followed by patients with genotype 4 and then patients with genotype 3, and it seems to have the least impact on patients with genotype 2 10, 12‐14…”

Section: Il‐28b In the Treatment Of Hcv Infectionsmentioning

confidence: 99%

Interleukin-28B polymorphism in hepatitis C and liver transplantation

2012

View full text Add to dashboard Cite

The discovery of interleukin-28B (IL-28B) single-nucleotide polymorphisms has opened an important new area of research in liver transplantation (LT) for hepatitis C virus (HCV). Both recipient-and donor-derived IL-28B genotypes affect the post-LT treatment response, with sustained virological response (SVR) rates oscillating from >50% in homozygotes for the favorable allele (up to 90% when this is present in both the recipient and the donor) to <15% in homozygotes for the unfavorable allele and from 30% to 50% in heterozygotes. Other key posttransplant outcomes affected by the IL-28B genotype are the time to histological recurrence, HCV RNA and alanine aminotransferase levels, histological variables (including the rate of fibrosis progression), and hepatocellular carcinoma. Interactions between donor and recipient IL-28B genotypes are complex and may affect outcomes not directly related to HCV infections, such as acute cellular rejection (ACR) and metabolic diseases. A preferential allocation system in which livers from donors homozygous for the favorable allele are given to HCV patients might be postulated to improve SVR rates and post-LT outcomes in recipients with HCV infections (a 25% increase in SVR and an 8% decrease in mortality at 5 years). Although negative effects from this are difficult to predict, they could include an accelerated progression of fibrosis in patients with failed HCV eradication and an increase in ACR in non-HCV patients. Our knowledge of the precise role of IL-28B genotypes in the course of post-LT HCV is evolving, but existing knowledge suggests the possibility of exploring strategies that use IL-28B genotyping to reduce the impact of post-LT adverse outcomes. Liver Transpl 19:49-58, 2012. V C 2012 AASLD.Received March 21, 2012; accepted July 30, 2012.The recent association of allelic variation in the interleukin-28B (IL-28B) gene with hepatitis C virus (HCV) eradication after antiviral therapy generated new insight into our understanding of the complex relationship between viral infections and the human immune system. 1 The discovery suggested the importance of type III or lambda interferons (IFNs) for mounting an effective immunological response against HCV, either spontaneously or after stimulation with peginterferon and ribavirin. The initial report showing that patients homozygous for the C single-nucleotide polymorphism (SNP) at position rs12979860 of chromosome 19q (corresponding to 3 kb upstream of the IL-28B gene) were 2 times more likely to achieve a sustained virological response (SVR) than patients with either the CT or TT variant 1 was rapidly followed by similar reports assessing SNPs within the same region of the IFN-k gene as well as their association with spontaneous viral clearance after acute HCV infections. [2][3][4][5] The study of IL-28B in HCV is particularly complicated for liver transplantation (LT) because recipients have 2 contributing sources of IL-28B genotypes: the recipient and the donor allograft. Thus, results from the nontransplant setting should not...

show abstract

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

Cited by 11 publications

References 30 publications

Prevalence of Hepatitis C Virus Subgenotypes 1a and 1b in Japanese Patients: Ultra-Deep Sequencing Analysis of HCV NS5B Genotype-Specific Region

Prevalence of Hepatitis C Virus Subgenotypes 1a and 1b in Japanese Patients: Ultra-Deep Sequencing Analysis of HCV NS5B Genotype-Specific Region

Pharmacogenomics of hepatitis C infections: personalizing therapy

Interleukin-28B polymorphism in hepatitis C and liver transplantation

Contact Info

Product

Resources

About