Janssen, HL, van Zonneveld, M, Senturk, H, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: A randomised 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
Source: PubMed

ABSTRACT 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 The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication.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.

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    • "Treatment options for chronic HBV infection include nucleos(t)ide analogs and interferon-based therapy [3] [4]. 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 [5]. 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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    ABSTRACT: Background 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. Objective 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. Results 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. Conclusions 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.
    Journal of Clinical Virology 12/2014; 61(4). DOI:10.1016/j.jcv.2014.08.008 · 3.47 Impact Factor
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    • "However, PEG- IFN a-2a monotherapy failed to reach the level of superiority of the combination therapy with regard to HBeAg seroconversion and virological response; HBeAg seroconversion occurred in 29–32% of patients treated with PEG-IFN a-2a monotherapy and in 27– 29% of patients who received combination therapy (Supplementary Table II). Therefore, the authors concluded that combination therapy with LVD does not yield additive effects, and this conclusion supported the use of PEG-IFN a-2a monotherapy as the first-line treatment [Janssen et al., 2005; Lau et al., 2005]. In contrast, by replacing LVD with ETV, HBeAg seroconversion was observed in 73% of study patients at the end of the follow-up phase (week 72) and virological response in 82% of HBeAg-positive patients, which is significantly higher than that in the previous report. "
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    ABSTRACT: The ideal approach to treat chronic hepatitis B remains controversial. This pilot study aimed to evaluate the effectiveness of peginterferon (PEG-IFN) α-2b and entecavir hydrate (ETV) as a combination therapy for patients with chronic hepatitis B, particularly in the context of virological response and the reduction of intrahepatic covalently closed circular DNA (cccDNA). A total of 17 patients with hepatitis B virus (HBV) genotype C were enrolled in this study. All subjects were treated with this combination therapy for 48 weeks and observed for an additional 24 weeks. All patients underwent liver biopsy before and after the therapy period. Changes in cccDNA levels and liver histology were monitored between biopsies. Among the 11 patients who exhibited pre-therapy hepatitis B e antigen (HBeAg), 8 (73%) showed evidence of HBeAg seroconversion by the end of the follow-up period. Serum HBV DNA levels decreased by 5.2 and 3.3 log copies/ml (mean) by the end of the therapy and follow-up periods, respectively. In addition, intrahepatic cccDNA decreased significantly to 1.4 log copies/µg (mean) by the end of the therapy period. Among the 11 patients who did not experience viral relapse, only 2 (18%) exhibited high levels of cccDNA (>4.5 log copies/µg) by the end of the treatment period. In contrast, all relapsed subjects exhibited significantly higher levels of cccDNA than subjects who did not relapse (P = 0.027). The combination regimen is a promising approach to treat chronic hepatitis B and may achieve significant reduction in serum HBV DNA and intrahepatic cccDNA. J. Med. Virol. 85: 987-995, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2013; 85(6):987-95. DOI:10.1002/jmv.23564 · 2.22 Impact Factor
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    • "HBeAg levels were assessed in HBeAg-positive CHB patients who were previously enrolled in an investigator-initiated international multicenter randomized controlled trial (Buster et al., 2008; Janssen et al., 2005). In-and exclusion criteria for this study have previously been described elsewhere (Janssen et al., 2005). Patients were treated with PEG-IFN alfa-2b 100 lg weekly (PegIntron, "
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    ABSTRACT: Hepatitis B e antigen (HBeAg) levels may predict response to peginterferon (PEG-IFN) but are also influenced by presence of precore(PC) and core promoter(BCP) mutants. HBeAg was measured in 214 patients treated with PEG-IFN±lamivudine for 52 weeks. Patients were classified at baseline as wildtype (WT) or non-WT (detectable PC/BCP mutants). Combined response (HBeAg loss with HBV DNA<2,000 IU/mL), HBeAg response (HBeAg loss with HBV DNA>2,000 IU/mL) or non-response was assessed at week 78. Mean baseline HBeAg levels were 2.65 logIU/mL in combined responders, 2.48 in non-responders and 2.24 in HBeAg responders(p=0.034). Baseline HBeAg levels were not associated with combined response after stratification by WT/non-WT. Within the PEG-IFN monotherapy group(n=104), patients with HBeAg <1 logIU/mL at week 24 had a higher probability of combined response (29% versus 12%,p=0.041). After stratification by WT/non-WT, WT patients with HBeAg <1logIU/mL at week 24 had a probability of combined response of 78% (versus 19% in patients with >1logIU/mL,p<0.001), whereas no difference in response rates was observed in non-WT patients (p=0.848). The relationship between HBeAg levels and response to PEG-IFN depends upon the presence of PC/BCP mutants. HBeAg levels should therefore not be routinely used to select patients for PEG-IFN, nor for monitoring of therapy.
    Antiviral research 12/2012; 97(3). DOI:10.1016/j.antiviral.2012.12.023 · 3.94 Impact Factor
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