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EFFECT OF ADVANCED FIBROSIS AND CIRRHOSIS ON HCV TREATMENT OUTCOME: RESULTS OF THE CANADIAN POWER PROGRAM
P Marotta, S Feinman, C Ghent, H Witt-Sullivan, L Scully, R Woolstencroft, R Bailey
London Health Sciences Centre, Mount Sinai Hospital, London, Ontario; Hamilton Health Sciences Corp., University of Ottawa, Schering-Plough Canada, University of Alberta
AIM: To determine the impact of advanced fibrosis/cirrhosis on SVR rates in treatment-naive patients with chronic hepatitis C who were treated with weight-based PEG-IFN alpha-2b and weight-based ribavirin (RBV) in a “real-life” clinical setting.
METHODS: Patients were treated with PEG-IFN alpha-2b (1.5µg/kg/wk) plus weight-based RBV (800-1200mg/d) as described previously. SVR was defined as undetectable HCV RNA 24 weeks post-treatment. Liver biopsy specimens were assigned a Metavir score of F1-F4.
RESULTS: This analysis involves 946 patients with liver biopsy specimens, including those who discontinued because of side effects or lack of response. Patients were excluded if they had undetectable HCV RNA at end of treatment but no 6-month follow up, had no treatment data available, or had HIV/HCV co-infection. Liver biopsy revealed F1-F2 fibrosis in 60% and F3-F4 fibrosis/cirrhosis in 40%. Overall SVR amongst patients with fibrosis data was 50% (475/946); SVR rates were significantly higher in patients with minimal fibrosis (F1-F2; N=568) than in those with advanced fibrosis/cirrhosis (F3-F4; N=378) (60% vs 35%, P<0.0001). The interaction between advanced disease and SVR was restricted to G1, as significantly higher SVR rates were attained in F1-F2 patients than F3-F4 patients (53% vs 23%, P<0.0001); this association was not evident in patients infected with either G2 (80% vs 78%, P=ns) or G3 (75% vs 63%, P=ns). G1 patients with F1-F2 fibrosis and low viral load (LVL; N=159) achieved significantly higher SVR rates than those with F1-F2 and high viral load (HVL; N=197) (63% vs 45%, P<0.001); however, the negative effect of HVL on SVR was not apparent amongst G1 patients with advanced fibrosis or cirrhosis (26% G1 LVL vs 29% G1 HVL, P=ns).
CONCLUSIONS: Advanced liver disease affects G1 SVR during PEG-IFN plus weight-based RBV therapy. HVL negatively impacts SVR rates in G1 patients with minimal fibrosis but not those with advanced disease. Patients with such disease characteristics warrant innovative therapeutic approaches, including modified dose and duration of treatment, to achieve improved outcomes.
Supported by Schering-Plough