Adding interferon to lamivudine enhances the early virologic response and reversion of the precore mutation in difficult-to-treat HBV infection
- 1 June 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in The Esophagus
- Vol. 43 (6), 457-463
- https://doi.org/10.1007/s00535-008-2174-9
Abstract
The virologic impact of adding interferon to antiviral nucleoside therapy was studied in Japanese patients having perinatally transmitted hepatitis B virus (HBV) genotype C. Sixty-four patients including 41 positive for hepatitis B e antigen (HBeAg) were assigned to receive either (1) a combination of interferon-α (6 million units daily for 2 weeks, then three times weekly) plus lamivudine (100 mg daily) for 24 weeks followed by lamivudine alone for 28 weeks (n = 30) or (2) 52-week lamivudine monotherapy (n = 34). The combination treatment enhanced the early virologic response, and HBV clearance was more frequent at week 8 for patients with baseline HBV DNA ≤ 7 log copies/ml (90% vs. 33%, P = 0.013) and at week 24 for patients with baseline HBV DNA > 7 log copies/ml (75% vs. 40%, P = 0.080). In the combination arm, YMDD mutants emerged less often at week 52 (8% vs. 30%, P = 0.047). However, reversion of the precore mutation was more prominent with combination treatment than with monotherapy (McNemar test, P = 0.014 and P = 0.103, respectively). HBeAg seroconversion (P = 0.429) and sustained off-treatment HBV suppression to ≤5 log copies/ml (log-rank test, P = 0.195) were not improved. Simultaneous commencement of treatment with interferon and a nucleoside analog may be worthy as a treatment option to augment the early virologic response and prevent drug resistance in difficult-to-treat patients. Combination treatment was also shown to enhance reversion of the precore mutation. Further studies are warranted to clarify the therapeutic implications of this phenomenon.Keywords
This publication has 19 references indexed in Scilit:
- Comparison of sequence changes of precore and core promoter regions in HBeAg-positive chronic hepatitis B patients with and without HBeAg clearance in lamivudine therapyJournal of Hepatology, 2006
- A viral kinetic study using pegylated interferon alfa-2b and/or lamivudine in patients with chronic hepatitis B/HBeAg negativeHepatology, 2005
- Lamivudine vs lamivudine and interferon combination treatment of HBeAg(-) chronic hepatitis BJournal of Viral Hepatitis, 2005
- Peginterferon Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients with HBeAg-Negative Chronic Hepatitis BNew England Journal of Medicine, 2004
- Identification of HBV DNA sequences that are predictive of response to lamivudine therapyHepatology, 2004
- Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapyHepatology, 2001
- Evolution of Hepatitis B Virus Polymerase Gene Mutations in Hepatitis B e Antigen–Negative Patients Receiving Lamivudine TherapyHepatology, 2000
- Reversion From Precore/Core Promoter Mutants to Wild-Type Hepatitis B Virus During the Course of Lamivudine TherapyHepatology, 2000
- Interferon‐α2a for chronic hepatitis B with e antigen or antibody: comparable antiviral effects on wild‐type virus and precore mutantJournal of Viral Hepatitis, 1995
- Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitisHepatology, 1981