Journal
JOURNAL OF HEPATOLOGY
Volume 56, Issue 3, Pages 557-563Publisher
ELSEVIER
DOI: 10.1016/j.jhep.2011.10.004
Keywords
IL28B gene; Hepatitis C virus; Viral kinetics; Single nucleotide polymorphism
Categories
Funding
- NIDDK [1 R01 DK066920-01, 1 K24 DK072036-01]
- NIDDK with Roche Laboratories, Inc. [U01 DK60329, U01 DK60340, U01 DK60324, U01 DK60344, U01 DK60327, U01 DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01 DK60346, U01 DK60349, U01 DK60341]
- National Center for Research Resources (NCRR) General Clinical Research Centers [M02 RR000079, M01 RR16500, M01 RR000042, M01 RR00046]
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Background & Aims: We studied the relationship between IL28B gene-related SNP rs12979860 and early viral kinetics (day 0-28) during peginterferon and ribavirin treatment, in 173 African Americans (AA) and 188 Caucasian Americans (CA) with HCV genotype 1. Methods: We studied the relationship between IL28B 16 gene-related SNP rs12979860 and early viral kinetics (day 0-28) 17 during peginterferon and ribavirin treatment, in 171 African 18 Americans (AA) and 188 Caucasian Americans (CA) with HCV 19 genotype 1. Results: Compared to non-C/C genotypes, C/C was associated with greater declines in serum HCV RNA during phase 1 (day 0-2), phase 2 (day 7-28), and day 0-28 and higher response (undetected HCV RNA) rates at weeks 4 and 12 in AA and CA. A static phase and increases in HCV RNA from day 2 to 7 were more common in patients with non-C/C genotypes. C/C was also associated with higher week 24, 48, and 72 response rates in CA (p<0.01) but not in AA. At baseline, SNP genotype was the only independent predictor of phase 1; SNP genotype and phase 1 were independent predictors of phase 2 (p<0.001). There were no racial differences in HCV RNA declines during phase 1, day 2-7, phase 2, and day 0-28 with the same SNP genotype. AA with C/C and C/T genotypes had lower week 24, 48, and 72 (SVR) rates than did CA (p = 0.03). SNP C/C predicted higher SVR rates in AA and CA with high baseline HCV RNA (>= 600,000 IU/ml), and in CA with >= 1 log(10) IU/ml decrease in HCV RNA from day 0 to 28. Conclusions: SNP rs12979860 is strongly associated with both phase 1 and phase 2 HCV RNA kinetics in AA and CA with HCV genotype 1. (C) 2012 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
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