Dataset Information

Interferon-λ-related genes and therapeutic response in Chinese hepatitis C patients.

ABSTRACT:

Aim

To determine the association between rapid viral response and IL28B, IL28RA, IL10RB and MxA polymorphisms in the Chinese Han population.

Methods

The study cohort consisted of 238 chronic hepatitis C patients treated with interferon (IFN)-α-2b and ribavirin. Six single nucleotide polymorphisms were genotyped using the ABI TaqMan allelic discrimination assay. Biochemical indices were measured at baseline. Serum hepatitis C virus (HCV) RNA was detected at weeks 0, 4, 12 and 24 of therapy.

Results

Only IL28B rs12980275 was associated with treatment response in the Chinese Han population. Patients carrying AG/GG genotypes had a reduced rapid viral response compared with patients carrying the AA genotype (additive model: adjusted OR = 0.43, 95%CI: 0.24-0.75). It took less time for patients with the AA genotype to achieve a viral load < 500 copies/mL (log-rank test, P = 0.004). In addition, the protective effect of genotype AA was independent of baseline viral load. HCV genotype, and baseline white blood cell count, α-fetoprotein and viral load might also help predict treatment response. The area under the receiver-operating characteristic curve was 0.726.

Conclusion

IL28B rs12980275 AA genotype is a strong predictor of positive response to IFN therapy in Chinese Han patients with hepatitis C.

SUBMITTER: Zhang YY

PROVIDER: S-EPMC4385550 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Publications

Interferon-λ-related genes and therapeutic response in Chinese hepatitis C patients.

Zhang Yuan-Yuan YY Chen Hong-Bo HB Xu Yin Y Huang Peng P Wang Jie J Zhang Yun Y Yu Rong-Bin RB Su Jing J

World journal of gastroenterology 20150401 13

<h4>Aim</h4>To determine the association between rapid viral response and IL28B, IL28RA, IL10RB and MxA polymorphisms in the Chinese Han population.<h4>Methods</h4>The study cohort consisted of 238 chronic hepatitis C patients treated with interferon (IFN)-α-2b and ribavirin. Six single nucleotide polymorphisms were genotyped using the ABI TaqMan allelic discrimination assay. Biochemical indices were measured at baseline. Serum hepatitis C virus (HCV) RNA was detected at weeks 0, 4, 12 and 24 of ...[more]

PMID: 25852288

Similar Datasets

Project description:AimTo evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-λ (IFNL) polymorphisms.MethodsThis study enrolled patients with chronic hepatitis C referred to the Tehran Blood Transfusion Hepatitis Clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type of pegylated interferon. Patients were treated with 180 μg pegylated interferon alpha-2a (Pegaferon(®)) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis C virus (HCV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL genotypes.ResultsA total of 152 patients with a mean age of 41.9 ± 10.0 years were included in the study, of which 141/152 were men (92.8%). The most frequent HCV genotype was type-1, infecting 93/152 (61.2%) patients. Sustained virologic response (SVR) was achieved in 81.9% of patients with HCV genotype-1 and 91.1% of patients with HCV genotype-3. Treatment success was achieved in 91.2% (52/57) of patients with the IFNL rs12979860 CC genotype and 82.1% (78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT (39/45; 86.7%) and non-TT (61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HCV RNA level, stage of liver fibrosis, rs12979860 CC genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 CC genotype was significantly associated with achievement of SVR (OR = 6.2; 95%CI: 1.2-31.9; P = 0.03).ConclusionThe rs12979860 CC genotype was associated with SVR in patients receiving pegylated interferon plus ribavirin, however, the SVR rate in other rs12979860 genotypes was also relatively high.

Project description:BackgroundIL28B gene polymorphism is the best baseline predictor of response to interferon alfa-based antiviral therapies in chronic hepatitis C. Recently, a new IFN-L4 polymorphism was identified as first potential functional variant for induction of IL28B expression. Individualization of interferon alfa-based therapies based on a combination of IL28B/IFN-L4 polymorphisms may help to optimize virologic outcome and economic resources.MethodsOptimization of treatment outcome prediction was assessed by combination of different IL28B and IFN-L4 polymorphisms in patients with chronic HCV genotype 1 (n = 385), 2/3 (n = 267), and 4 (n = 220) infection treated with pegylated interferon alfa (PEG-IFN) and ribavirin with (n = 79) or without telaprevir. Healthy people from Germany (n = 283) and Egypt (n = 96) served as controls.ResultsFrequencies of beneficial IL28B rs12979860 C/C genotypes were lower in HCV genotype 1/4 infected patients in comparison to controls (20-35% vs. 46-47%) this was also true for ss469415590 TT/TT (20-35% vs. 45-47%). Single interferon-lambda SNPs (rs12979860, rs8099917, ss469415590) correlated with sustained virologic response (SVR) in genotype 1, 3, and 4 infected patients while no association was observed for genotype 2. Interestingly, in genotype 3 infected patients, best SVR prediction was based on IFN-L4 genotype. Prediction of SVR with high accuracy (71-96%) was possible in genotype 1, 2, 3 and 4 infected patients who received PEG-IFN/ribavirin combination therapy by selection of beneficial IL28B rs12979860 C/C and/or ss469415590 TT/TT genotypes (p<0.001). For triple therapy with first generation protease inhibitors (PIs) (boceprevir, telaprevir) prediction of high SVR (90%) rates was based on the presence of at least one beneficial genotype of the 3 IFN-lambda SNPs.ConclusionIFN-L4 seems to be the best single predictor of SVR in genotype 3 infected patients. For optimized prediction of SVR by treatment with dual combination or first generation PI triple therapies, grouping of interferon-lambda haplotypes may be helpful with positive predictive values of 71-96%.

Dataset Information

Interferon-λ-related genes and therapeutic response in Chinese hepatitis C patients.

Aim

Methods

Results

Conclusion

Publications

Interferon-λ-related genes and therapeutic response in Chinese hepatitis C patients.

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