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Differences between Hepatitis B and C in the Prediction of Success of Treatment Using Early Viral Kinetics
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Reported by Jules Levin
AU Neuman, Bar-Ilan University, Ramat-Gan, Israel
Early Hepatitis C viral (HCV) kinetics was previously shown to predict sustained virological response (SVR). However, its predictive value for pegylated-IFN and ribavirin treatment is not yet established. Moreover, early viral kinetics predictors of HBeAg loss during antiviral therapy of HBeAg+ Chronic Hepatitis B patients are not yet well identified.
(HCV): 134 chronically infected naïve patients received peginterferon-alfa-2a (40KD) (Pegasys) (180 ug qw) plus ribavirin (Copegus) 1000-1200 mg qd) for 48 weeks. Of those, 67%, 28%, 4% and 1% had HCV genotype 1, 2-3, 4, or 5 respectively. Viral kinetics were measured according to centralized serum HCV RNA quantifications on days 0, 1, 4, 7, 8, 15, 22 and 29 (Cobas Amplicor HCV Monitor v2 Roche).
(HBV): 129 HBeAg-positive patients were treated for 48 weeks with adefovir 10mg/day. HBV DNA monitored every 4 weeks (Amplicor). HBV DNA at week 1 was estimated by log-linear regression.
For HCV we find that a composite 2nd phase slope criteria can predict SVR with NPV (negative predictive value)=100% and specificity=34% already after 4 weeks of treatment.
Furthermore, prediction with NPV=100% and specificity=28% can be obtained already at week 1. Combining both criteria allows to increase specificity up to 50%. Moreover, by selecting more strict thresholds for the above criteria one obtains PPV (positive predictive value)=94%.
For HBV two major patterns were identified during weeks 4-48: a flat second phase (RF) or a slow second phase decline (RS) in 35% and 65% of patients, respectively. This slow second phase was then followed by three different third phases: HBV DNA became undetectable (<400 copies/ml) (RSBD) in 35%, or had a staircase pattern (RSFS) in 28% of RF patients. No patients with RF pattern as identified at 48 weeks lost HBeAg during the same period, compared to 28%, 43%, and 77% of the RSBD groups. However, when the RF pattern was identified at 16 weeks we find that 10% of early RF patients had HBeAg loss at 16-48 weeks.
HCV sustained viral response to treatment with peginterferon-alfa and ribavirin can be predicted, independent of genotype, as early as 1 or 4 weeks of treatment. On the other hand, the earliest HBV kinetics can predict HBeAg loss is at 16 weeks. Moreover, changes in HBV kinetics patterns occur even after that time making the prediction of end-pont less accurate. This may indicate that HBV has more dynamical viral dynamics as compared to HCV, and that processes triggered later on during HBV treatment can influence response to treatment, while the fate of HCV treatment is determined by early kinetic events.
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