Factors That Predict Response of Patients With Hepatitis B e Antigen–Positive Chronic Hepatitis B to Peginterferon-Alfa
Background & Aims
Therapy with pegylated interferon (PEG-IFN)–alfa results in sustained response in a minority of patients with chronic hepatitis B virus (HBV) infection and has considerable side effects. We analyzed data from the 2 largest global trials of hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B to determine which are most likely to respond to PEG-IFN–alfa therapy.
Methods
The study included 542 patients treated with PEG-IFN–alfa-2a (180 μg/wk, 48 wk) and 266 patients treated with PEG-IFN–alfa-2b (100 μg/wk, 52 wk). Eighty-seven patients were excluded, leaving 721 patients for analysis. A sustained response was defined as HBeAg loss and HBV-DNA level less than 2.0 × 103 IU/mL 6 months after treatment. Logistic regression analysis was used to identify predictors of sustained response and a multivariable model was constructed.
Results
HBV genotype, high levels of alanine aminotransferase (ALT; ≥2 × upper limit of normal), low levels of HBV DNA (<2.0 × 108 IU/mL), female sex, older age, and absence of previous IFN therapy predicted a sustained response. Genotype A patients with high ALT and/or low HBV-DNA levels had a high predicted probability (>30%) of a sustained response. The strongest predictors of response were a high level of ALT in genotype B patients and a low level of HBV DNA in genotype C patients. Genotype D patients had a low chance of sustained response, irrespective of ALT or HBV-DNA levels.
Conclusions
The best candidates for a sustained response to PEG-IFN–alfa are genotype A patients with high levels of ALT or low levels of HBV DNA, and genotypes B and C patients who have both high levels of ALT and low HBV DNA. Genotype D patients have a low chance of sustained response.
Abbreviations used in this paper: ALT, alanine aminotransferase, AUC, area under the receiver-operating characteristic curve, CI, confidence interval, HBeAg, hepatitis B e antigen, HBV, hepatitis B virus, HCC, hepatocellular carcinoma, OR, odds ratio, PEG-IFN, peginterferon, ULN, upper limit of normal
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Funding The Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study was supported by a research grant from Roche (Basel, Switzerland). The HBV99-01 study was organized and sponsored by the Foundation for Liver Research (SLO), Rotterdam, The Netherlands. Financial support and study medication for the HBV99-01 study was provided by Schering-Plough International (Kenilworth, NJ) and GlaxoSmithKline (Greenford, UK).
Conflicts of interest These authors disclose the following: Erik H.C.J. Buster received speaker's honoraria from Novartis and Roche; George K. Lau consulted for Roche and Novartis; Teerha Piratvisuth consulted for GlaxoSmithKline, Novartis, and Schering-Plough, and received research support from Roche and Bristol-Myers Squibb; Stefan Zeuzem was a consultant for Bristol-Myers Squibb, Gilead, Novartis, Roche, and Schering-Plough, was on the speaker's bureau for Gilead and Novartis, and received research support from Roche; Harry L. A. Janssen received research support from Bristol-Myers Squibb, Gilead, Novartis, Roche, Schering-Plough, and was a consultant for Bristol-Myers Squibb, Novartis, and Roche. The remaining authors disclose no conflicts. Potential investigator conflicts of interest have not been disclosed to study participants.
PII: S0016-5085(09)01551-0
doi:10.1053/j.gastro.2009.08.061
© 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
