Prediction of response to pegylated-interferon-α and ribavirin therapy in Chinese patients infected with different hepatitis C virus genotype.
BACKGROUND
The standard treatment for patients with chronic hepatitis C (CHC), pegylated interferon-α (PEG-IFN) plus ribavirin (RBV) does not provide a sustained virological response (SVR) in all patients. Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy in CHC patients.


RESULTS
We investigated the role of IL28B variations (rs8099917) in response to PEG-IFN-α/RBV treatment and evaluated its association with the risk of the null virological response (NVR) and relapse (REL) in different viral genotypes. We found that the overall distributions of the genotype among the SVR, NVR, and REL groups were significantly different (P < 0.001). Patients with the TG genotype had an increased risk of NVR and REL (OR = 6.45 95% CI = 2.88-14.47, P < 0.001 for NVR; OR = 2.51, 95% CI = 1.29-4.86, P = 0.006 for REL, respectively), and patients with the GG genotype had a further increased risk of NVR and REL (OR = 12.04, 95% CI = 3.21-45.13, P < 0.001 for NVR; ,OR = 4.30, 95% CI = 1.21-15.13, P = 0.017 for REL, respectively). G variant genotypes (TG+GG) also had an increased risk of NVR and REL, and there was a significant trend for a dose-effect of G allele on the risk of NVR and REL (P < 0.05). The SVR rate in TT higher than in TG+GG was more pronounced in those patients infected with non-G1 compared to the patients infected with G1. The treatment response did differ based on the rs8099917 genotype in patients with different viral genotypes, compared with patients infected with the non-G1, the G1 infected patients had an increased risk of NVR and REL (OR = 2.03 95% CI = 1.03-4.01, P = 0.04 for NVR and OR = 2.58, 95% CI = 1.35-4.94, P = 0.004 for REL, respectively). Moreover, multivariate regression analysis show that the rs8099917 G allele was the only independent factor significantly associated with a NVR and REL.


CONCLUSIONS
This study suggests that host genetic polymorphisms rs8099917 in the vicinity of IL-28B is the most important predictor of treatment response of PEG-IFN-α/RBV for HCV patients in China.
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tian He Road, Guangzhou 510630, PR China.
Xiaoyan
X
Guo
Zhixin
Z
Zhao
Junqiang
J
Xie
Qingxian
Q
Cai
Xiaohong
X
Zhang
Liang
L
Peng
Zhiliang
Z
Gao
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002681:China; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda