• Mazen Noureddin M.D.,

  • Elizabeth C. Wright M.D.,

  • Marc G. Ghany M.D.

  • Potential conflict of interest: Nothing to report.

We appreciate the insightful comments by Grebely et al. regarding the role of HCV RNA levels on disease outcome among persons with advanced chronic hepatitis C virus (HCV).[1] We performed the requested analysis to address the issue. HCV RNA levels were available on all patients from the HALT-C cohort but only from 108 of the 246 patients from the NIH cohort. In the cross-sectional analysis, the mean HCV RNA level was higher between the HALT-C cohort compared to the NIH cohort, 6.40 log10 IU/mL (SD 0.56) versus 5.58 log10 IU/mL (SD 0.90), P < 0.0001, respectively. For both cohorts combined, HCV RNA levels were higher among patients with IL28B CC genotype (6.39 log10 IU/mL, SD 0.78) compared to IL28B TT genotype (6.23 log10 IU/mL, SD 0.53), P = 0.0013, but not IL28B CT genotype (6.34 log10 IU/mL, SD 0.59), P = 0.28. When CC was compared to CT and TT combined (mean 6.31, SD 0.78), the P-value was 0.087. Analyzing the two cohorts separately revealed no difference between IL28B genotypes CC and CT/TT in the NIH cohort, 5.51 log10 IU/mL (SD 1.00) for those with CC and 5.63 log10 IU/mL (SD 0.83) for those with IL28B CT/TT, P = 0.52. However, in the HALT-C cohort the mean was 6.53 log10 IU/mL (SD 0.64) for those with IL28B genotype CC and 6.35 (SD 0.53) for those with genotype CT/TT, P < 0.0001. The observation that HCV RNA levels did not differ between IL28B CC and non-CC genotypes in the NIH cohort could have been due to the small sample size.

Importantly, in multivariate analysis, HCV RNA levels were neither associated with fibrosis progression (P = 0.61) nor clinical outcomes (P = 0.75). Thus, while we found HCV RNA levels to be higher among patients with IL28CC genotype, as demonstrated previously by Grebely et al.,[2] they did not influence fibrosis progression or clinical outcomes. Further studies are needed to investigate why patients with IL28 CC genotype have worse clinical outcomes compared to non-CC patients.


This research was supported by the Intramural Research Program of the NIDDK, NIH.

  • Mazen Noureddin, M.D.1

  • Elizabeth C. Wright, M.D.2

  • Marc G. Ghany, M.D.1

  • 1Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

  • 2Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD