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


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 The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication.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 · 3.02 Impact Factor
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    • "Although the initial trials of PEG-IFN and lamivudine failed to show that the combination therapy was superior to IFN monotherapy [28,59], a retrospective analysis of HBeAg positive patients revealed a more significant decline of HBsAg levels on treatment with PEG-IFN plus lamivudine compared with PEG-IFN only [38]. "
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    ABSTRACT: Chronic hepatitis B virus (HBV) infection can result in liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). However, the natural course of the disease is highly dynamic and not every patient requires therapy. The challenges for optimal management are who to treat, which therapeutic regimen to use, and when to begin or stop treatment. Constant monitoring is mandatory to predict the natural course and guide treatment decisions. Surrogate markers for baseline and on treatment decisions are needed. Besides HBV DNA, hepatitis B surface antigen levels also proved to be useful to help judge the natural course and guide treatment. High levels of HBsAg are suggestive of low fibrosis and immune tolerance in hepatitis B e antigen (HBeAg) positive patients; whereas low levels of HBsAg indicate a lower risk for HCC and inactive carrier state in HBeAg negative patients. Data also support the possible use of HBsAg levels as an on-treatment response marker. So far, the best evidence exists for treatment with interferon (IFN)-α where lack of HBsAg decline after 12 weeks is associated with non-response. Thus, stopping rules after 12 weeks therapy could be established for HBeAg positive as well as for HBeAg negative patients. However, the positive predictive value for achieving sustained response is still vague. The value of HBsAg monitoring is less clear during treatment with nucleos(t)ide analogues (NA) but it can be a useful marker for new concepts such as stopping NA or add-on IFN strategies. Currently, several studies are underway to validate HBsAg in these settings.
    Annals of Gastroenterology 03/2014; 27(2):105-112.
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    • "According to the literature, HBeAg seroconversion to anti-HBe occurs in up to 30% of monoinfected individuals in use of pegylated interferon and in up to 28% of coinfected individuals in use of conventional interferon-alpha [8,11,13,14]. Furthermore, HBsAg seroconversion to anti-HBs occurs in less than 10% of the monoinfected and probably in a much smaller proportion of coinfected individuals [15]. "
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    ABSTRACT: Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm3), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.
    Journal of Venomous Animals and Toxins including Tropical Diseases 12/2013; 19(1):31. DOI:10.1186/1678-9199-19-31 · 0.80 Impact Factor
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