Genetic polymorphism in IL28B predicts null virological response to pegylated-interferon plus ribavirin therapy for chronic hepatitis C

  • Kurosaki M
  • Tanaka Y
  • Nishida N
  • et al.
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Abstract

Background and Aims: Some patients infected with genotype 1b hepatitis C virus (HCV) have null virological response (NVR) to peg-interferon plus ribavirin therapy. A reliable predictor of NVR could avoid the unpleasant side effects and cost of treatment. This study aimed to develop a model for the pre-treatment prediction of NVR and sustained virological response (SVR) using host and viral factors. Methods: Data was collected from a total of 246 chronic hepatitis C patients with genotype 1b who were treated with peg-interferon alpha and ribavirin at 5 hospitals and universities throughout Japan. Homozygotes or heterozygotes of minor sequence in one tagging SNP located within IL28B (rs8099917) was defined as having IL28B minor allele, whereas homozygotes for major sequence was defined as having IL28B major allele. IL28B polymorphism, substitutions in HCV core and NS5A, and clinical features were analyzed to predict NVR and SVR. Decision models of NVR were determined by classification and regression tree analysis using IBM-SPSS modeler. Results: Logistic regression analysis revealed that IL28B minor allele (OR=29.73 95%CI = 12.55-70.41, p<0.0001) and female gender (OR=3.25, 95%CI = 1.39-7.58, p=0.006) was independently associated with NVR. The decision model revealed that females with minor IL28B allele had the highest probability of NVR (81%). Females with major IL28B allele had 29% probability of NVR when position 91 of HCV core was methionine and 12% probability of NVR when it was leucine. Males with minor IL28B allele had 67% probability of NVR, whereas males with major IL28B allele had the lowest probability (4%). The reproducibility of the model was confirmed (r2 = 0.999, p<0.001). For the prediction of SVR, IL28B major allele (OR=10.99, 95%CI = 4.78-25.0, p<0.0001), HCVRNA <600,000IU/ml (OR = 2.30, 95% CI = 1.06-5.0, p = 0.04), and platelets (OR=1.07, 95%CI = 1.01-1.14, p=0.03) was independently associated with SVR. Conclusions: The present study highlighted the impact of IL28B polymorphism, gender and the substitutions in HCV core on pretreatment predictions of NVR. The decision model, including these host and viral factors has the potential to support the clinical decision of selecting patients with a high probability of NVR to wait for more effective future therapy.

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Kurosaki, M., Tanaka, Y., Nishida, N., Sugiyama, M., Matsuura, K., Asahina, Y., … Mizokami, M. (2010). Genetic polymorphism in IL28B predicts null virological response to pegylated-interferon plus ribavirin therapy for chronic hepatitis C. Journal of Hepatology, 52, S451–S452. https://doi.org/http://dx.doi.org/10.1016/S0168-8278%2810%2961170-1

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