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      HBsAg and HBeAg in the prediction of a clinical response to peginterferon α-2b therapy in Chinese HBeAg-positive patients

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          Abstract

          Background

          This study aimed to evaluate the predictive values of hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) levels in 171 Chinese patients with chronic hepatitis B who received a 48-week course of pegylated interferon alfa-2b therapy at 1.5 mcg/kg.

          Methods

          HBsAg, HBeAg, and hepatitis B virus (HBV) DNA levels were measured at baseline and weeks 12, 24, 48, and 72. Clinical responses were defined as a combined response (CR, HBeAg seroconversion [sustained response, SR] combined with HBV DNA level <2,000 IU/mL at week 72). The positive predictive value and negative predictive value were calculated for HBsAg alone and/or combined with HBeAg and HBV DNA at weeks 12 and 24.

          Results

          Of 171 patients included, 58 (33.9 %) achieved a SR. Of patients who achieved a SR, 33 (56.9 %) achieved a CR. Totally 19.3 % (33/171) patients achieved CR and 80.7 % (138/171) patients did not. Patients with HBsAg <1500 IU/mL at week 12 had a 47.4 % chance of achieving an off-treatment SR and patients with a HBsAg decrease >1.5 logIU/mL at week 12 had a 54.5 % chance. Patients with HBsAg >20,000 IU/mL at weeks 12 and 24 had a 93.8 and 100.0 % chance, respectively, of not achieving a CR. An HBsAg level or changes at weeks 12 and 24, combined with HBeAg or HBV DNA, increased the chance for a SR and CR.

          Conclusions

          On-treatment HBsAg quantification, alone or in combination with HBeAg or HBV DNA, predicted off-treatment SR and CR after 48 weeks of PEG-IFNα-2b therapy, and thus, may guide clinicians in making a therapeutic decision to continue or terminate the therapy.

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          Most cited references26

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          Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination.

          To determine the prevalence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti-HBc) in a representative population in China 14 years after introduction of hepatitis B vaccination of infants. National serosurvey, with participants selected by multi-stage random sampling. Demographics and hepatitis B vaccination history collected by questionnaire and review of vaccination records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA. The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese population aged 1-59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg prevalence was greatly diminished among those age <15 years compared to that found in the 1992 national serosurvey, and among children age <5 years was only 1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with vaccination among all age groups. HBsAg risk in adults was associated with male sex, Western region, and certain ethnic groups and occupations while risk in children included birth at home or smaller hospitals, older age, and certain ethnic groups (Zhuang and other). China has already reached the national goal of reducing HBsAg prevalence to less than 1% among children under 5 years and has prevented an estimated 16-20 million HBV carriers through hepatitis B vaccination of infants. Immunization program should be further strengthened to reach those remaining at highest risk.
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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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              Viral hepatitis B.

              More than 400 million people worldwide are chronically infected by the hepatitis B virus. The virus is responsible for more than 300000 cases of liver cancer every year and for similar numbers of gastrointestinal haemorrhage and ascites. Major breakthroughs have been achieved in diagnosis and treatment of this virus. Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C, advances have been made in molecular virology, especially for naturally occurring and treatment-induced mutant viruses. The clinical significance of low viral load and genotypes are also under investigation. Currently available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis. Lamivudine, and presumably other nucleoside analogues, can reverse cirrhosis of the liver.
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                Author and article information

                Contributors
                sduyangsong@163.com
                hchxing@sohu.com
                wym417@163.com
                jlhousmu@aliyun.com
                luoduande@hotmail.com
                xieqingrjh@163.com
                qning@tjh.tjmu.edu.cn
                renhong0531@vip.sina.com.cn
                dinghuiguo@medmail.com.cn
                shengji.fang@163.com
                weelai@163.com
                csj7516@sina.com
                fanxl2001@163.com
                wenxiang_huang@163.com
                panchencry@163.com
                zlgao99@hotmail.com
                jmzhang@fudan.edu.cn
                zhoubp@hotmail.com
                bjchen302@aliyun.com
                mobinwan@aliyun.com
                htang6198@hotmail.com
                wanggq@hotmail.com
                yangyuxiu55@126.com
                xudongping@yahoo.com
                peilingdong@sohu.com
                qi.xin.wang@merck.com
                jue.wang2@merck.com
                fernando.bognar@merck.com
                xudaozhen@126.com
                +86-10-84322291 , jun.cheng.ditan@gmail.com , chengj0817@sina.cn
                Journal
                Virol J
                Virol. J
                Virology Journal
                BioMed Central (London )
                1743-422X
                28 October 2016
                28 October 2016
                2016
                : 13
                : 180
                Affiliations
                [1 ]Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, 100015 China
                [2 ]Southwest Hospital Affiliated Third Military Medical University, Shapingba, Chongqing 400038 China
                [3 ]Guangzhou Nanfang Hospital, Guangzhou, 510515 China
                [4 ]Xiehe Hospital Affiliated Tongji Medical College of Huazhong University of Science & Technology, Wuhan, 430022 China
                [5 ]Shanghai Ruijin Hospital affilated Shanghai Jiaotong University School of Medicine, Shanghai, 200025 China
                [6 ]Tongji Hospital Affiliated Tongji Medical College of Huazhong University of Science & Technology, Wuhan, 430030 China
                [7 ]The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010 China
                [8 ]Beijing You’an Hospital, Capital Medical University, Fengtai District, Beijing, 100069 China
                [9 ]The First Affiliated Hospital of Zhejiang University Medical College, Hangzhou, 310003 China
                [10 ]Peking University People’s Hospital, Beijing, 100044 China
                [11 ]Jinan Infectious Disease Hospital, Jinan, 250021 China
                [12 ]No. 1 Hospital of Chongqing Medical University, Chongqing, 400016 China
                [13 ]Fuzhou Infectious Disease Hospital, Gulou District, Fuzhou, 350025 China
                [14 ]The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630 China
                [15 ]Huashan Hospital, Fudan University, Shanghai, 200040 China
                [16 ]Shenzhen Donghu Hospital, Shenzhen, 518020 China
                [17 ]Beijing 302 Hospital, Beijing, 100039 China
                [18 ]Shanghai Changhai Hospital, Shanghai, 200433 China
                [19 ]West China Hospital, Sichuan University, Chengdu, 610041 China
                [20 ]Peking University First Hospital, Beijing, 100034 China
                [21 ]Henan Provincial People’s Hospital, Zhengzhou, 450003 China
                [22 ]Merck, Sharp & Dohme, Shanghai, 200040 China
                [23 ]Merck Sharp & Dohme Corp., 600 Corporate Drive, Lebanon, NJ 08833 USA
                Article
                640
                10.1186/s12985-016-0640-1
                5084370
                27793166
                2b507f75-5419-4c65-b343-7077fb57a6ac
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 14 April 2016
                : 19 October 2016
                Funding
                Funded by: MSD, Special Fund for the Development of Capital Medicine
                Award ID: 2011-2017-02
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Microbiology & Virology
                chronic hepatitis b,hepatitis b surface antigen (hbsag),peginterferon alfa-2b,hepatitis b e antigen (hbeag),combined response (cr)

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