Importance of Host Genetic Factors HLA and IL28B as Predictors of Response to Pegylated Interferon and Ribavirin

Rueda, Paloma; López-Nevot, Miguel-Ángel; Sáenz-López, Pablo; Casado, J.; Martín-Casares, Antonia María; Palomares, Pablo; Quiles-Pérez, Rosa; Gila, A.; Romero‐Gómez, Manuel; Pavón, Esther-José; Muñoz, J.E. Domínguez; Carazo, Ángel; Sanz-Cameno, Paloma; Moreno–Otero, Ricardo; Diago, M.; León, Josefa; Ruiz-Extremera, Ángeles; Salmerón, Javier

doi:10.1038/ajg.2011.82

Cited by 31 publications

(21 citation statements)

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“…These mothers were characterized by low viral load and by the absence of any increase in ALT levels after delivery. These findings are in accordance with those of previous studies, which have identified the main risk factors for perinatal mother-to-child transmission of HCV as the high concentration of HCV-RNA in maternal blood and HIV co-infection [25]. Two studies have shown that high ALT levels in the serum during pregnancy and at delivery are associated with higher rates of HCV-VT [42], [43].…”

Section: Discussionsupporting

confidence: 92%

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Variation of Transaminases, HCV-RNA Levels and Th1/Th2 Cytokine Production during the Post-Partum Period in Pregnant Women with Chronic Hepatitis C

et al. 2013

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This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

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Section: Discussionsupporting

confidence: 92%

“…Rs12979860 genotyping was performed by means of a Taqman 5′ allelic discrimination assay (Custom Assay Service, Applied Biosystems, Foster City, CA, USA) as described previously [24], [25].…”

Section: Methodsmentioning

confidence: 99%

Variation of Transaminases, HCV-RNA Levels and Th1/Th2 Cytokine Production during the Post-Partum Period in Pregnant Women with Chronic Hepatitis C

et al. 2013

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“…This variant is near the IL28B loci, which encodes type III IFN-k3 [14]. In a previous study, we showed that the HLA-DQB1 ⁄ 0301 allele and the IL28B polymorphisms rs12979860 are significant independent predictors of response to pegIFN-a/RBV in patients with CHC [15].…”

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confidence: 98%

Importance of IL-10 and IL-6 during chronic hepatitis c genotype-1 treatment and their relation with IL28B

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“…However, Chinese patients with DRB1*07 allele presented almost complete response to treatment, while DRB1*04 is associated with no responsiveness [19]. Another study showed that HLA-DQB1*0301 allele is associated with SVR; also there is a synergism between the HLA-DQB1*0301 and HLA-A*0201 alleles increasing the SVR rate [20]. Finally in a recent Egyptian study, HLA DRB1*01, DQB1*03, and DQB1*05 alleles were associated with viral clearance, while DRB1*7 and DQB1*02 alleles were associated with viral persistence [21].…”

Section: Introductionmentioning

confidence: 99%

Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1) as Predictors for Response to Interferon Therapy in HCV Genotype 4

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Bassiony

Raziky

et al. 2013

Mediators of Inflammation

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Human leukocyte antigens class II play an important role in immune response against HCV. We investigated whether HLA class II alleles influence susceptibility to HCV infection and response to interferon therapy. HLA-DRB1 and -DQB1 loci were genotyped using PCR-SSO Luminex technology. According to our regimen, 41 (66%) of patients achieved sustained virological response to combined treatment of IFN and ribavirin. Frequencies of DQB1∗0313 allele and DRB1∗04-DRB1∗11, DQB1∗0204-DQB1∗0313, DQB1∗0309-DQB1∗0313, and DQB1∗0313-DQB1∗0319 haplotypes were significantly more frequent in nonresponders than in responders. In contrast, DQB1∗02, DQB1∗06, DRB1∗13, and DRB1∗15 alleles were significantly more frequent in responders than in nonresponders. Similarly, DRB1∗1301, DRB1∗1361, and DRB1∗1369 alleles and DRB1∗1301-DRB1∗1328, DRB1∗1301-DRB1∗1361, DRB1∗1301-DRB1∗1369, DRB1∗1328-DRB1∗1361, and DRB1∗1328-DRB1∗1369 haplotypes were significantly found only in responders. Some alleles and linkages showed significantly different distributions between patient and healthy groups. These alleles may be used as predictors for response to treatment or to susceptibility to HCV infection in the Egyptian population.

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Importance of Host Genetic Factors HLA and IL28B as Predictors of Response to Pegylated Interferon and Ribavirin

Abstract: The HLA-DQB10301 allele and IL28B genotype are factors that are associated independently with SVR. There is a synergism between the HLA-DQB10301 and HLA-A*0201 alleles with polymorphism rs12979860 CC, which increases the SVR rate. IL28B genotype is the best predictor of SVR.

Cited by 31 publications

References 31 publications

Variation of Transaminases, HCV-RNA Levels and Th1/Th2 Cytokine Production during the Post-Partum Period in Pregnant Women with Chronic Hepatitis C

Variation of Transaminases, HCV-RNA Levels and Th1/Th2 Cytokine Production during the Post-Partum Period in Pregnant Women with Chronic Hepatitis C

Importance of IL-10 and IL-6 during chronic hepatitis c genotype-1 treatment and their relation with IL28B

Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1) as Predictors for Response to Interferon Therapy in HCV Genotype 4

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Importance of Host Genetic Factors HLA and IL28B as Predictors of Response to Pegylated Interferon and Ribavirin

Abstract: The HLA-DQB1*0301 allele and IL28B genotype are factors that are associated independently with SVR. There is a synergism between the HLA-DQB1*0301 and HLA-A*0201 alleles with polymorphism rs12979860 CC, which increases the SVR rate. IL28B genotype is the best predictor of SVR.

Cited by 31 publications

References 31 publications

Variation of Transaminases, HCV-RNA Levels and Th1/Th2 Cytokine Production during the Post-Partum Period in Pregnant Women with Chronic Hepatitis C

Variation of Transaminases, HCV-RNA Levels and Th1/Th2 Cytokine Production during the Post-Partum Period in Pregnant Women with Chronic Hepatitis C

Importance of IL-10 and IL-6 during chronic hepatitis c genotype-1 treatment and their relation with IL28B

Human Leukocyte Antigen Class II Alleles (DQB1 and DRB1) as Predictors for Response to Interferon Therapy in HCV Genotype 4

Contact Info

Product

Resources

About

Abstract: The HLA-DQB10301 allele and IL28B genotype are factors that are associated independently with SVR. There is a synergism between the HLA-DQB10301 and HLA-A*0201 alleles with polymorphism rs12979860 CC, which increases the SVR rate. IL28B genotype is the best predictor of SVR.