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      Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

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          Abstract

          Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included.

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          Most cited references97

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          Chronic hepatitis B.

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            Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.

            Current treatments for chronic hepatitis B are suboptimal. In the search for improved therapies, we compared the efficacy and safety of pegylated interferon alfa plus lamivudine, pegylated interferon alfa without lamivudine, and lamivudine alone for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. A total of 814 patients with HBeAg-positive chronic hepatitis B received either peginterferon alfa-2a (180 microg once weekly) plus oral placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), or lamivudine alone. The majority of patients in the study were Asian (87 percent). Most patients were infected with hepatitis B virus (HBV) genotype B or C. Patients were treated for 48 weeks and followed for an additional 24 weeks. After 24 weeks of follow-up, significantly more patients who received peginterferon alfa-2a monotherapy or peginterferon alfa-2a plus lamivudine than those who received lamivudine monotherapy had HBeAg seroconversion (32 percent vs. 19 percent [P<0.001] and 27 percent vs. 19 percent [P=0.02], respectively) or HBV DNA levels below 100,000 copies per milliliter (32 percent vs. 22 percent [P=0.01] and 34 percent vs. 22 percent [P=0.003], respectively). Sixteen patients receiving peginterferon alfa-2a (alone or in combination) had hepatitis B surface antigen (HBsAg) seroconversion, as compared with 0 in the group receiving lamivudine alone (P=0.001). The most common adverse events were those known to occur with therapies based on interferon alfa. Serious adverse events occurred in 4 percent, 6 percent, and 2 percent of patients receiving peginterferon alfa-2a monotherapy, combination therapy, and lamivudine monotherapy, respectively. Two patients receiving lamivudine monotherapy had irreversible liver failure after the cessation of treatment--one underwent liver transplantation, and the other died. In patients with HBeAg-positive chronic hepatitis B, peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion.
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              Hepatitis B e antigen and the risk of hepatocellular carcinoma.

              The presence of hepatitis B e antigen (HBeAg) in serum indicates active viral replication in hepatocytes. HBeAg is thus a surrogate marker for the presence of hepatitis B virus DNA. We conducted a prospective study to determine the relation between positivity for hepatitis B surface antigen (HBsAg) and HBeAg and the development of hepatocellular carcinoma. In 1991 and 1992, we enrolled 11,893 men without evidence of hepatocellular carcinoma (age range, 30 to 65 years) from seven townships in Taiwan. Serum samples obtained at the time of enrollment were tested for HBsAg and HBeAg by radioimmunoassay. The diagnosis of hepatocellular carcinoma was ascertained through data linkage with the computerized National Cancer Registry in Taiwan and with death certificates. We performed a multiple regression analysis to determine the relative risk of hepatocellular carcinoma among men who were positive for HBsAg alone or for HBsAg and HBeAg, as compared with those who were negative for both. There were 111 cases of newly diagnosed hepatocellular carcinoma during 92,359 person-years of follow-up. The incidence rate of hepatocellular carcinoma was 1169 cases per 100,000 person-years among men who were positive for both HBsAg and HBeAg, 324 per 100,000 person-years for those who were positive for HBsAg only, and 39 per 100,000 person-years for those who were negative for both. After adjustment for age, sex, the presence or absence of antibodies against hepatitis C virus, cigarette-smoking status, and use or nonuse of alcohol, the relative risk of hepatocellular carcinoma was 9.6 (95 percent confidence interval, 6.0 to 15.2) among men who were positive for HBsAg alone and 60.2 (95 percent confidence interval, 35.5 to 102.1) among those who were positive for both HBsAg and HBeAg, as compared with men who were negative for both. Positivity for HBeAg is associated with an increased risk of hepatocellular carcinoma. Copyright 2002 Massachusetts Medical Society.
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                Author and article information

                Contributors
                liveryfl@so-net.net.tw
                leungwyn@ha.org.hk , nancyleung@cuhk.edu.hk
                kaojh@ntu.edu.tw
                teerha.p@psu.ac.th
                EdGane@adhb.govt.nz
                gihankhys@yuhs.ac
                rgyc5@singnet.com.sg
                gkklau@netvigator.com
                Stephen.Locarnini@mh.org.au
                Journal
                Hepatol Int
                Hepatology International
                Springer-Verlag (New York )
                1936-0533
                1936-0541
                10 May 2008
                September 2008
                : 2
                : 3
                : 263-283
                Affiliations
                [1 ]Liver Research Unit, Chang Gung University and Memorial Hospital, 199, Tung Hwa North Road, Taipei, Taiwan
                [2 ]Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Room 65, J6, 11 Chuen On Road, Taipo, NT Hong Kong
                [3 ]Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan
                [4 ]NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, 90110 Thailand
                [5 ]NZ Liver Transplant Unit, Auckland, New Zealand
                [6 ]Department of Internal Medicine, Yonsei University College of Medicine, Liver Cirrhosis Clinical Research Center, Seoul, Korea
                [7 ]Mount Elizabeth Medical Centre and National University Hospital Singapore, 3 Mt Elizabeth, #17-02, Singapore, 228570 Singapore
                [8 ]Department of Medicine, The University of Hong Kong, Room 1838, Block K, Queen Mary Hospital, 102 Pokfulum Road, Hong Kong SAR, China
                [9 ]Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, WHO Collaborating Centre for Virus Reference & Research, 10 Wreckyn Street, North Melbourne, VIC 3051 Australia
                Article
                9080
                10.1007/s12072-008-9080-3
                2716890
                19669255
                0422694c-4e39-4ed9-a421-9b30455009c0
                © The Author(s) 2008
                History
                : 24 January 2008
                : 9 April 2008
                Categories
                Review Article
                Custom metadata
                © Asian Pacific Association for the Study of the Liver 2008

                Gastroenterology & Hepatology
                telbivudine,chronic hepatitis b,hepatocellular carcinoma,interferon-α,lamivudine,hepatitis b virus (hbv),liver cirrhosis,entecavir,adefovir,pegylated interferon

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