IFN-stimulated Gene Expression Is a Useful Potential Molecular Marker of Response to Antiviral Treatment with Peg-IFNα 2b and Ribavirin in Patients with Hepatitis C Virus Genotype 1

Sixtos-Alonso, M.S.; Sánchez‐Muñoz, Fausto; Sánchez-Ávila, Juan Francisco; Martínez, Rosalba Avalos; López, Aaron Domínguez; Vorácková, Florencia Vargas; Uribe, Misael

doi:10.1016/j.arcmed.2011.01.001

Cited by 14 publications

(12 citation statements)

References 20 publications

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“…Counterintuitively, preactivation of the endogenous IFN system, observed as an increased expression of hepatic ISGs before treatment of patients with CHC, is associated with less frequent achievement of SVR to Peg-IFN and ribavirin therapy [13–15]. Our results confirm these observations.…”

Section: Discussionsupporting

confidence: 84%

“…Our results confirm these observations. Patients who had not achieved EVR had higher expression of IFI27 (alpha-inducible protein 27), a gene from the group of ISGs, which have been shown in numerous studies to be of great prognostic importance [15, 20, 21]. …”

Section: Discussionmentioning

confidence: 99%

“…ISG products are responsible for the antiviral, antiproliferative and immunomodulatory properties of IFN. It appears that lower expression of ISGs in liver biopsy specimens evaluated before therapy corresponds with a better response to treatment [13–15]. …”

Section: Introductionmentioning

confidence: 99%

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Expression of selected genes in liver biopsy specimens in relation to early virological response in patients with chronic hepatitis C with HCV mono- and HIV/HCV co-infection

et al. 2013

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The aim of our study was to evaluate the significance of IL-28B single-nucleotide polymorphism and hepatic expression of IFI27, SOCS3 and miR-122 in order to predict early virological response (EVR) in patients infected with HCV genotype 1 or 4. The study group consisted of 65 patients: 46 with HCV mono- and 19 with HIV/HCV co-infection. Analyses of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood and expression of SOCS3, IFI27 and miR-122 in liver biopsy samples obtained before PegIFN and ribavirin treatment were performed by the RT-PCR method. EVR was defined as a >2log decline in HCV viremia at week 12. EVR was associated with a lower expression of IFI27 and a more frequent presence of the IL28BCC genotype. IFI27 expression was lower in patients with the CC genotype, irrespective of EVR. In multivariate logistic regression, only IL28B CC genotype and age above 40 years influenced EVR (OR =5.09 and 0.29 respectively). In contrast to IFI27, expression of miR-122 and SOCS3 in patients with different IL28B genotypes was not statistically significantly different. A correlation between miR-122 and SOCS3 was found (Rho =0.495094 p< 0.0001). Analysis of IFI27, SOCS3 and miR-122 hepatic expression does not provide substantial benefits for the prognosis of EVR. The only independent prognostic factors for EVR are age and IL28B genotype. The prognostic significance of IFI27 expression for EVR is dependent on the genetic polymorphism of IL28B.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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Expression of selected genes in liver biopsy specimens in relation to early virological response in patients with chronic hepatitis C with HCV mono- and HIV/HCV co-infection

et al. 2013

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“…It can inhibit cap-dependent protein synthesis by binding to the subunits of translation initiation complex elF3[25,37]. Researches has demonstrated that IFIT1 can restrict HCV growth by inhibiting HCV replication, and the expression level of IFIT1 can be potential biomarker of response to IFNα in patients with HCV[29,38]. IFIT1 restricts the translation and replication of many other viruses such as HPV, HIV and alphavirus, and promotes the induction of IFNα to enhance immune response[18,39,40].…”

Section: Discussionmentioning

confidence: 99%

“…All the evidences indicate that IFIT1 is an important effector in both virus infection and IFNα treatment. It has been reported that IFIT1 acts as a potential biomarker for Peg-IFNα treatment efficiency in hepatitis C virus (HCV) patients[29]. However, few researches mention about IFIT1’s role in HBV infected patients who treated with IFNα.…”

Section: Introductionmentioning

confidence: 99%

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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Individualized Therapy for Hepatitis C Infection: Focus on the Interleukin-28B Polymorphism in Directing Therapy

2013

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Hepatitis C virus—a major global cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma—affects millions of people worldwide. Pegylated interferon (Peg-IFN) and ribavirin (RBV) had been the standard treatment for a decade until availability of the protease inhibitors in 2011. However, current antiviral therapy is still IFN-based and is associated with significant side effects and variable treatment response. Thus, various host and viral factors have been evaluated before and during treatment for the prediction of sustained virologic response to antiviral therapy. In 2009, genome-wide association studies found the single-nucleotide polymorphisms, located near the host interleukin-28B (IL28B) gene that encodes IFN-λ3, to be the best pretreatment predictor of virologic response to Peg-IFN and RBV therapy in chronic hepatitis C genotype 1 patients. Additionally, inosine triphosphatase (ITPA) gene variants were found to be associated with RBV-induced hemolytic anemia, which could affect treatment dose for selected patients. IL28B, ITPA, and other treatment predictors allowed for a potential individualized approach to treat hepatitis C. In the era of increased overall virologic response rates and good tolerability of the rapidly developing non-IFN oral direct-acting antiviral therapy regimens, the need for individualized treatment is likely to diminish. Various predictors of response, including IL28B will likely be of reduced importance in the near future.

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IFN-stimulated Gene Expression Is a Useful Potential Molecular Marker of Response to Antiviral Treatment with Peg-IFNα 2b and Ribavirin in Patients with Hepatitis C Virus Genotype 1

Cited by 14 publications

References 20 publications

Expression of selected genes in liver biopsy specimens in relation to early virological response in patients with chronic hepatitis C with HCV mono- and HIV/HCV co-infection

Expression of selected genes in liver biopsy specimens in relation to early virological response in patients with chronic hepatitis C with HCV mono- and HIV/HCV co-infection

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

Individualized Therapy for Hepatitis C Infection: Focus on the Interleukin-28B Polymorphism in Directing Therapy

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