Background & Aims
The impact of fibrosis stage on chronic hepatitis C virus (HCV) treatment response
was explored in CHARIOT, a study of high dose peginterferon alfa-2a (PEG-IFNα-2a)
induction therapy in treatment naïve genotype 1 infection.
Methods
Eight hundred and ninety-six patients were randomised 1:1 to 360 μg (n = 448) or 180 μg (n = 448) PEG-IFNα-2a weekly with RBV 1000–1200 mg/day for 12 weeks followed by 36 weeks of 180 μg PEG-IFNα-2a weekly plus RBV 1000–1200 mg/day. Virological responses were assessed at week 4, 8, 12, 24, 48 (end of therapy),
and 24 weeks following therapy (sustained virological response, SVR). As previously reported,
there was no significant difference in SVR in the induction (53%) and standard (50%)
arms, therefore the pooled study population was used for analysis of SVR and relapse.
Results
A marked step-wise decline in SVR was evident by fibrosis stage: F0 (70%); F1 (60%);
F2 (51%); F3 (31%); F4 (10%) (p <0.0001). Early virological responses were lower among F3/4 patients, including rapid
virological response (RVR) (21% vs. 34% for F3/4 and F0–2, respectively) (p = 0.0072), and the RVR positive predictive value was also lower (63% vs. 80%). Virological
relapse rates were similar in early disease stages (F0, 16%; F1, 23%; F2, 26%), but
increased markedly in advanced fibrosis (F3, 50%; F4, 80%) (p <0.0001). Cumulative PEG-IFNα-2a and ribavirin doses were similar among patients with
F3/4 and F0–2 within treatment arms through week 4, 8, 12, and week 24.
Conclusions
Low virological response in hepatitis C genotype 1 patients with advanced fibrosis
is not explained by inadequate cumulative PEG-IFN and ribavirin doses.
Keywords
Abbreviations:
CHC (chronic hepatitis C), HCV (hepatitis C virus), SVR (sustained virological response), RVR (rapid virological response), EVR (early virological response), PPV (positive predictive value), NPV (negative predictive value)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: June 23, 2010
Accepted:
April 11,
2010
Received in revised form:
March 19,
2010
Received:
November 12,
2009
Identification
Copyright
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
