‘Easy to treat’ genotypes were not created equal: Can rapid virological response (RVR) level the playing field?

Duarte‐Rojo, Andrés; Heathcote, E. Jenny; Feld, Jordan J.

doi:10.1016/j.jhep.2011.02.004

Cited by 9 publications

(10 citation statements)

References 81 publications

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“…IFN‐λ signalling is initiated through a membrane receptor system complex distinct from that of IFN‐α, but has biological activities similar to those of IFN‐α/β . Its expression depends on the same stimuli and signal transduction pathways as those involved in IFN‐α/β, which leads to induction of several hundred IFN‐stimulated genes (ISG) . Although it is well known that genotypes 2 and 3 are more responsive to IFN than genotype 1, the mechanisms by which the genotype interferes with the response to anti‐viral treatment remain speculative.…”

Section: Discussionmentioning

confidence: 99%

“…Although it is well known that genotypes 2 and 3 are more responsive to IFN than genotype 1, the mechanisms by which the genotype interferes with the response to anti‐viral treatment remain speculative. One hypothesis is that certain viral genotypes (like genotype 1) are inherently more likely to induce ISG preactivation, which prevents further induction with IFN‐based therapy and reduces the chances of a virological response . As increased levels of ISG preactivation have been observed in the presence of unfavourable IL28B variants, this hypothesis offers an explanation linking genotype, IL28B polymorphisms, ISG preactivation levels, and the likelihood of a virological response.…”

Section: Discussionmentioning

confidence: 99%

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Meta‐analysis: the impact of IL28B polymorphisms on rapid and sustained virological response in HCV‐2 and ‐3 patients

Schreiber

Moreno

Garcia

et al. 2012

Aliment Pharmacol Ther

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Meta‐analysis: the impact of IL28B polymorphisms on rapid and sustained virological response in HCV‐2 and ‐3 patients

Schreiber

Moreno

Garcia

et al. 2012

Aliment Pharmacol Ther

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“…48 Therefore, virological response at week 4 of dual PEG-IFN and RBV therapy could be crucial in differentiating easy-to-treat from difficult-to-treat genotype 3 patients. 49 In contrast, the NORDynamIC trial observed that treatment for 12 weeks in HCV-3 was generally inferior to 24 weeks (SVR 58% after 12 weeks, 78% after 24 weeks). 50 Similarly, the N-CORE study showed that extended duration of treatment in non-RVR patients provided benefits in HCV-3 patients adherent to study protocol with SVR24 of 73% following 48 weeks of treatment and 54% after 24-week treatment duration.…”

Section: Current Treatment In Hcv-3mentioning

confidence: 97%

“…As such, it has been suggested that HCV‐3 patients with RVR could be treated for 12 weeks, whereas in those without RVR, it was felt preferable to extend treatment to 36 weeks . Therefore, virological response at week 4 of dual PEG‐IFN and RBV therapy could be crucial in differentiating easy‐to‐treat from difficult‐to‐treat genotype 3 patients . In contrast, the NORDynamIC trial observed that treatment for 12 weeks in HCV‐3 was generally inferior to 24 weeks (SVR 58% after 12 weeks, 78% after 24 weeks) .…”

Section: Current Treatment In Hcv‐3mentioning

confidence: 99%

Review article: HCV genotype 3 – the new treatment challenge

Ampuero

Romero‐Gómez

Reddy

2014

Aliment Pharmacol Ther

103

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Summary Background Over the past several years, hepatitis C therapy has been pegylated interferon and ribavirin based. Although protease inhibitor‐based therapy has enhanced response rates in genotype 1, the recent advances in therapy have demonstrated a challenge in genotype 3, a highly prevalent infection globally. Aim To provide a comprehensive summary of the literature evaluating the unique characteristics and evolving therapies in genotype 3. Methods A structured search in PubMed, the Cochrane Library and EMBASE was performed using defined key words, including only full text papers and abstracts in English. Results HCV genotype 3 is more prevalent in Asia and among intra‐venous drug users. Furthermore, it interferes with lipid and glucose metabolism, and the natural history involves a more rapid progression of liver disease and a higher incidence of hepatocellular carcinoma (HCC). New therapies with protease inhibitors have focused on genotype 1 largely and have demonstrated enhanced responses, but have limited activity against genotype 3. Thus far, in clinical trials, NS5B and NS5A inhibitors have performed more poorly in genotype 3, while a cyclophilin inhibitor, alisporivir, has shown promise. Conclusions As treatments for HCV have evolved, genotype 3 has become the most difficult to treat. Furthermore, genotype 3 has special characteristics, such as insulin resistance and alterations in lipid metabolism, which may partly explain the lower treatment responses. A great deal of emphasis on advancing therapy is needed in this population that appears to have a more rapid progression of liver disease and a higher incidence of HCC.

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“…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

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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...

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‘Easy to treat’ genotypes were not created equal: Can rapid virological response (RVR) level the playing field?

Cited by 9 publications

References 81 publications

Meta‐analysis: the impact of IL28B polymorphisms on rapid and sustained virological response in HCV‐2 and ‐3 patients

Meta‐analysis: the impact of IL28B polymorphisms on rapid and sustained virological response in HCV‐2 and ‐3 patients

Review article: HCV genotype 3 – the new treatment challenge

Interleukin-28B polymorphism in hepatitis C and liver transplantation

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