Jansen, HL, Von Zonneveld, M, Senturk, H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg positive chronic hepatitis B: A randomized trial. Lancet 2005;365:123-129
Department of Gastroenterology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. The Lancet
(Impact Factor: 45.22).
01/2005; 365(9454):123-9. DOI: 10.1016/S0140-6736(05)17701-0
Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response.
307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 microg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 microg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment.
49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%).
Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.
Available from: Huimin Yan
- "Pegylated interferon-alpha 2a (IFN-a) is recommended for the treatment of chronic hepatitis B (CHB) in the current consensus guidelines of many countries. Compared with conventional recombinant IFN-a, however, pegylated IFN-a alone or in combination with nucleoside analogues does not significantly increase the rate of sustained response (Janssen et al., 2005; Lau et al., 2005). "
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ABSTRACT: Chronic hepatitis B (CHB) is currently treated with IFN-α and nucleos(t)ide analogues, which have many clinical benefits, but there is no ultimate cure. The major problem consists in the persistence of cccDNA in infected hepatocytes. Because no antiviral drug has been evaluated which significantly reduces copies of cccDNA, cytolytic and noncytolytic approaches are needed. Effective virus-specific T- and B-cell responses remain crucial in eliminating cccDNA-carrying hepatocytes and for the long-term control of HBV infection. Reduction of viremia by antiviral drugs provides a window for reconstitution of an HBV-specific immune response. Preclinical studies in mice and woodchucks have shown that immunostimulatory strategies, such as prime-boost vaccination and PD-1 blockade, can boost a weak virus-specific T cell response and lead to effective control of HBV infection. Based on data obtained in our preclinical studies, the combination of antiviral drugs and immunomodulators may control HBV viremia during a patient's drug-off period. In this article, we review current immune-modulatory approaches for the treatment of chronic hepatitis B and the elimination of cccDNA in preclinical models. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis".
Available from: Ju-Tao Guo
- "e l s e v i e r . c o m / l o c a t e / a n t i v i r a l as hepatitis e antigen (HBeAg) seroconversion and/or reduction in HBV DNA levels to below 20,000 copies/mL at 6 months after the completion of a 48-week course of therapy – in only 30% of HBeAg-positive and 40% of HBeAg-negative cases (Janssen et al., 2005; Lau et al., 2005; Perrillo, 2009). Nucleos(t)ide analogs profoundly reduce the viral load in vast majority of treated patients, which is associated with significant improvement of liver function and reduced incidence of liver failure and hepatocellular carcinoma (Liaw, 2013). "
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ABSTRACT: Persistent hepatitis B virus (HBV) infection relies on the stable maintenance and proper functioning of a nuclear episomal form of the viral genome called covalently closed circular (ccc) DNA. One of the major reasons for the failure of currently available antiviral therapeutics to achieve a cure of chronic HBV infection is their inability to eradicate or inactivate cccDNA. In this review article, we summarize our current understanding of cccDNA metabolism in hepatocytes and the modulation of cccDNA by host pathophysiological and immunological cues. Perspectives on the future investigation of cccDNA biology, as well as strategies and progress in therapeutic elimination and/or transcriptional silencing of cccDNA through rational design and phenotypic screenings, are also discussed. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B."
Copyright © 2015. Published by Elsevier B.V.
Available from: Richard Guan
- "Treatment options for chronic HBV infection include nucleos(t)ide analogs and interferon-based therapy  . In mainland China, the approved dosage of peginterferon (PEG-IFN) alfa-2b is 1.0 g/kg/wk for 24 weeks; however, studies of this regimen for durations of up to 52 weeks have generally yielded relatively modest antiviral effects . Establishing the optimum dose and treatment duration for PEG-IFN alfa-2b is therefore imperative to maximize the clinical utility of this treatment. "
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In mainland China, peginterferon (PEG-IFN) alfa-2b 1.0 μg/kg/wk for 24 weeks is the approved treatment for HBeAg-positive chronic hepatitis B.
This multicenter, randomized trial evaluated the safety and efficacy of regimens utilizing increased dose or treatment duration in treatment-naive Chinese patients with chronic hepatitis B.
Study design: 670 HBeAg-positive patients from China, Malaysia, Taiwan area, Singapore, and Thailand were enrolled. Patients received PEG-IFN alfa-2b 1.0 μg/kg/wk (arm A) or 1.5 μg/kg/wk (arm B) for 24 weeks, or 1.5 μg/kg/wk for 48 weeks (arm C). The primary end point was loss of HBeAg 24 weeks after end of treatment.
At the end of follow-up, HBeAg loss was significantly greater in arm C compared with arm A (31.3% vs 17.3%; P = 0.001) and arm B (31.3% vs 18.1%; P = 0.001). No significant difference in the rate of HBeAg loss was observed between arms A and B. The proportions of patients with HBe seroconversion, HBV DNA levels <20,000 IU/mL, and ALT normalization at the end of follow-up were significantly higher in arm C compared with arm A and arm B. In arms A, B, and C, rates of early treatment discontinuation were 6.3%, 4.9%, and 8.9%; of discontinuation due to an AE, 2%, 3%, and 3%; and of AEs requiring dose modification, 3%, 6%, and 10%, respectively.
In Chinese patients with HBeAg-positive chronic hepatitis B, PEG-IFN alfa-2b 1.5 μg/kg/wk for 48 weeks is more efficacious compared with 1.0 and 1.5 μg/kg/wk for 24 weeks.
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