Genetic Variants of Interferon-Stimulated Genes and IL-28B as Host Prognostic Factors of Response to Combination Treatment for Chronic Hepatitis C

López‐Rodríguez, Rosario; Trapero-Marugán, María; Borque, M.J.; Román, Manuel; Hernández-Bartolomé, Ángel; Rodríguez-Muñoz, Y.; Martı́n-Vı́lchez, Samuel; Abad‐Santos, Francisco; Rueda, Paloma; Vidal-Castiñeira, José Ramón; Rodrigo, Luís; Salmerón, Javier; Moreno–Otero, Ricardo; Sanz-Cameno, Paloma

doi:10.1038/clpt.2011.189

Cited by 19 publications

(14 citation statements)

References 39 publications

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“…Other study by our group has described the influence of KIR genes on the progression of chronic HCV infection and treatment outcome [29]. As well as KIR receptors, other genetic markers related to immune response have been reported [42]. One such marker is PDCD1 , which allowed us to develop a model for predicting the response to conventional therapy.…”

Section: Discussionmentioning

confidence: 99%

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Diversity of Killer Cell Immunoglobulin-Like Receptor (KIR) Genotypes and KIR2DL2/3 Variants in HCV Treatment Outcome

et al. 2014

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The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2*001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p<0.05) and KIR2DL3*001 was associated with sustained viral response (SVR) (41.6% vs. 61.2%, p<0.005). The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs. 45.7%, p<0.001). From the frequencies of KIR obtained, 35 genotypes were assigned on the basis of previous studies. The centromeric A/A genotype was more frequent in SVR (44.1% vs. 34.5%, p<0.005) and the centromeric B/B genotype was found to be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001). The logic regression model showed the importance of KIR genes in predicting the response to combined treatment, since the positive predictive value (PPV) was improved (from 55.9% to 75.3%) when the analysis of KIR was included in addition to the IFNL3 rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for predicting the combined treatment response in patients with chronic HCV infection in association with the determination of IFNL3 polymorphism.

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Section: Discussionmentioning

confidence: 99%

“…Previous studies have described several biomarkers of treatment response in addition to IFNL3 polymorphisms [41], [42]. Other study by our group has described the influence of KIR genes on the progression of chronic HCV infection and treatment outcome [29].…”

Section: Discussionmentioning

confidence: 99%

Diversity of Killer Cell Immunoglobulin-Like Receptor (KIR) Genotypes and KIR2DL2/3 Variants in HCV Treatment Outcome

et al. 2014

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“…However, no evidence was found to support that variants on IFIT1 facilitated gene splicing or gene expression. A recent research showed that a variant known as rs304478, which located within 2 kb upstream of IFIT1 , was an independent predictive factor for pegylated-IFN therapy in HCV patients[44]. Although rs304478 was not included in the present study due to its relative lower MAF in Chinese population, it highlighted a fact that IFIT1 could be potential biomarker for IFNα treatment efficiency.…”

Section: Discussionmentioning

confidence: 87%

IFIT1polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

Xie¹,

Wang²,

Yang³

et al. 2016

WJG

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AIMTo investigate the association between interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) polymorphisms and interferon-α (IFNα) treatment efficiency among Chinese hepatitis B virus (HBV) infection patients.METHODSTwo hundred and twenty five newly diagnosed chronic hepatitis B (CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen (HBeAg) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms (SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTSAt the end of the treatment, HBeAg seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218 (A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64 (95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response (response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype (response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBeAg seroconversion, combined response or sustained response was observed.CONCLUSIONIFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.

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“…The allele OASL rs12819210 constitutes an important independent factor that is significantly associated with SVR in peg-IFN-plus-ribavirin treatment, notably improving the predictive value of IL-28B rs12979860. In addition to OASL and IL-28B, the IFIT1 rs304478 A/A genotype favors a better therapy outcome, especially in patients with HCV-1 [136]. …”

Section: Polymorphisms In Host Response Genesmentioning

confidence: 99%

Glances in Immunology of HIV and HCV Infection

Quaranta

Mattioli

Vella

2012

Advances in Virology

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Since the identification of HIV and HCV much progress has been made in the understanding of their life cycle and interaction with the host immune system. Despite these viruses markedly differ in their virological properties and in their pathogenesis, they share many common features in their immune escape and survival strategy. Both viruses have developed sophisticated ways to subvert and antagonize host innate and adaptive immune responses. In the last years, much effort has been done in the study of the AIDS pathogenesis and in the development of efficient treatment strategies, and a fatal infection has been transformed in a potentially chronic pathology. Much of this knowledge is now being transferred in the HCV research field, especially in the development of new drugs, although a big difference still remains between the outcome of the two infections, being HCV eradicable after treatment, whereas HIV eradication remains at present unachievable due to the establishment of reservoirs. In this review, we present current knowledge on innate and adaptive immune recognition and activation during HIV and HCV mono-infections and evasion strategies. We also discuss the genetic associations between components of the immune system, the course of infection, and the outcome of the therapies.

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Genetic Variants of Interferon-Stimulated Genes and IL-28B as Host Prognostic Factors of Response to Combination Treatment for Chronic Hepatitis C

Cited by 19 publications

References 39 publications

Diversity of Killer Cell Immunoglobulin-Like Receptor (KIR) Genotypes and KIR2DL2/3 Variants in HCV Treatment Outcome

Diversity of Killer Cell Immunoglobulin-Like Receptor (KIR) Genotypes and KIR2DL2/3 Variants in HCV Treatment Outcome

IFIT1polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

Glances in Immunology of HIV and HCV Infection

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