Advanced fibrosis in genotype 1 HCV infected patients receiving antiviral therapy is associated with virologic relapse independent of rapid (RVR) and early (EVR) virologic response.

Abstract

Background: The CHARIOT study examined induction vs. standard PegIFN alpha-2a (40KD) dosing in HCV G1 infected patients (pts) and highlighted a significantly lower SVR in pts with advanced fibrosis than in many pivotal studies. This seemed to be due to higher relapse rate of 50% in pts with advanced fibrosis (F3/4). Thus the aim of this analysis was to examine virological relapse at greater depth in the CHARIOT cohort. Method(s): A multiple logistic regression (MLR) analysis was performed with relapse rate (RR) as the outcome variable. The explanatory variables included baseline demographics, treatment group, viral and liver disease characteristics, and laboratory parameters. Result(s): Baseline liver histology was obtained in 625 of 871 (72%) pts. Of the 625 pts, 127 (20%) had advanced fibrosis (F3/4) and 498 (80%) had no to moderate fibrosis (F0-2). The SVR rate for F3/4 pts (26%) was significantly lower than for F0-2 pts (57%) (p < 0.001). The RR following end of treatment response (EOTR) was significantly greater in F3/4 pts (33/66) than F0-2 pts (62/338), (50% vs 18% respectively, p = <0.001). In the MLR analysis, baseline variables significantly associated with relapse were age (OR=1.07, 95%CI=1.03-1.11, p<0.001), log HCV RNA (OR=1.78, 1.15-2.76, p=0.01), log ALT quotient (OR=0.07, 0.01-0.31, p<0.001), log gammaGT (OR=4.40, 1.48-13.0, p=0.008) and advanced fibrosis (OR=4.24, 1.79-10.0, p=0.001). The Table shows RR and SVR by on-treatment viral responses according to fibrosis stage. A second MLR analysis examined RR as the outcome variable with baseline variables as above plus early on treatment response: RVR, complete (cEVR) excluding those with RVR, and combined pEVR and nonresponse (NR) at 12 weeks. Variables that remained significantly associated with RR were: age (OR=1.07, 1.02-1.11, p=0.003), log ALT quotient (OR=0.14, 0.03-0.79, p=0.025), early on treatment predictors (RVR vs pEVR or NR: OR=0.07, 0.02-0.21, cEVR vs pEVR or NR: OR=0.38, 0.16-0.92, p<0.001) and advanced fibrosis (OR=4.17, 1.59-10, p=0.003). Therefore the odds that a patient with F3/4 has a relapse are about 4 times greater than the odds of relapse for a patient with no or mild fibrosis. Conclusion(s): Fibrosis status (F3/4 vs. F0-2) was still significant in MLR for virological relapse adjusted by baseline characteristics and early virologic response predictors. This finding is not explained by current paradigms of predictors of SVR. (Table Presented).