Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing

Cheng, Wendy S.C.; Roberts, Stuart K.; McCaughan, Geoffrey; Sievert, William; Weltman, Martin; Crawford, Darrell; Rawlinson, William; Marks, Philippa S.; Thommes, James; Rizkalla, Bishoy; Yoshihara, Motoko; Dore, Gregory J; on behalf of the CHARIOT Study Group,

doi:10.1016/j.jhep.2010.04.024

« Previous Next »Journal of Hepatology
Volume 53, Issue 4 , Pages 616-623, October 2010

Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing

Wendy S.C. Cheng
- Royal Perth Hospital, Perth, Australia
Stuart K. Roberts
- Alfred Hospital, Melbourne, Australia
Geoffrey McCaughan
- Royal Prince Alfred Hospital, Sydney, Australia
William Sievert
- Monash Medical Centre and Monash University, Melbourne, Australia
Martin Weltman
- Nepean Hospital, Sydney, Australia
Darrell Crawford
- Greenslopes Hospital, Brisbane, Australia
William Rawlinson
- SEALS Microbiology, Prince of Wales Hospital, Sydney, Australia
Philippa S. Marks
- National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
James Thommes
- Roche Products, Nutley, NJ, USA
Bishoy Rizkalla
- Roche Products, Sydney, Australia
Motoko Yoshihara
- Roche Products, Sydney, Australia
Gregory J Dore
- National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
- St. Vincent’s Hospital, Sydney, Australia
- Corresponding author. Address: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, CFI Building, Corner Boundary and West Streets, Darlinghurst, NSW 2010, Australia. Tel.: +61 2 9385 0900; fax: +61 2 9385 0876.
on behalf of the CHARIOT Study Group

Received 12 November 2009; received in revised form 19 March 2010; accepted 11 April 2010. published online 23 June 2010.

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 360μg (n=448) or 180μg (n=448) PEG-IFNα-2a weekly with RBV 1000–1200mg/day for 12weeks followed by 36weeks of 180μg PEG-IFNα-2a weekly plus RBV 1000–1200mg/day. Virological responses were assessed at week 4, 8, 12, 24, 48 (end of therapy), and 24weeks 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: Pegylated interferon, Ribavirin, Adherence, Fibrosis, Cirrhosis

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