Rapid virological response is the most important predictor of sustained virological response across genotypes in patients with chronic hepatitis C virus infection

Journal of Hepatology
Volume 55, Issue 1, Pages 69-75 (July 2011)

Michael W. Fried 1, Stephanos J. Hadziyannis 2, Mitchell L. Shiffman 3, Diethelm Messinger 4, Stefan Zeuzem 5

Received 21 June 2010; received in revised form 12 October 2010; accepted 18 October 2010. published online 09 December 2010.

Background & Aims
The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR.

Methods
A retrospective analysis of 1383 patients, encompassing genotypes 1–4, treated with peginterferon alfa-2a and ribavirin, was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with RVR were identified. The relative significance of RVR compared to other baseline factors for predicting SVR was analyzed by multiple logistic regression analysis.

Results
RVR was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively. Among patients who achieved RVR, the rate of SVR was high across all genotypes and ranged from 88% to 100% (genotypes 1–4). Baseline factors predictive of RVR included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age. Notably, the presence of RVR generated the highest odds ratio (5.47, 95% confidence interval 3.97–7.52) for predicting SVR in multiple logistic regression analysis of these factors.

Conclusions
Attainment of RVR varies by genotype and is associated with several baseline factors. Patients who achieve RVR have the highest rates of SVR, regardless of genotype. These findings have important implications for predicting and managing response-guided combination antiviral therapies.

1 University of North Carolina, Chapel Hill, NC 27599, USA
2 Henry Dunant Hospital, Athens, Greece
3 Bon Secours Health System, Liver Institute of Virginia, Newport News, VA, USA
4 IST, Mannheim, Germany
5 J.W. Goethe University Hospital, Frankfurt, Germany

Corresponding author. Address: University of North Carolina at Chapel Hill, CB# 7584, Room 8015 Burnett-Womack Building, Chapel Hill, NC 27599, USA. Tel.: +1 919 966 2516 fax: +1 919 966 1700.

PII: S0168-8278(10)01093-7
doi:10.1016/j.jhep.2010.10.032
© 2011 Published by Elsevier Inc.

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