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Chronic hepatitis B virus infection and total and cause-specific mortality: a prospective cohort study of 0.5 million people
  1. Jiahui Si1,
  2. Canqing Yu1,
  3. Yu Guo2,
  4. Zheng Bian2,
  5. Ruogu Meng1,
  6. Ling Yang3,
  7. Yiping Chen3,
  8. Jianrong Jin4,
  9. Jingchao Liu4,
  10. Ziyan Guo5,
  11. Junshi Chen6,
  12. Zhengming Chen3,
  13. Jun Lv1,7,
  14. Liming Li1,2
  15. on behalf of the China Kadoorie Biobank Collaborative Group
    1. 1 Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
    2. 2 Chinese Academy of Medical Sciences, Beijing, China
    3. 3 Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
    4. 4 Wuzhong Center for Disease Control & Prevention, Suzhou, China
    5. 5 Nangang Center for Disease Control & Prevention, Harbin, China
    6. 6 China National Center for Food Safety Risk Assessment, Beijing, China
    7. 7 Peking University Institute of Environmental Medicine, Peking University, Beijing, China
    1. Correspondence to Dr Jun Lv; lvjun{at} and Dr Liming Li; lmlee{at}


    Objectives Chronic hepatitis B virus (HBV) infection is associated with a higher risk of liver diseases. Substantial uncertainty remains, however, about the associations of HBV infection with mortality from extrahepatic causes, especially from subtypes of cardiovascular diseases. We prospectively examined the association of chronic HBV infection with total and cause-specific mortality.

    Design Population-based prospective cohort study.

    Setting China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.

    Participants 475 801 participants 30–79 years of age without reporting major chronic diseases at baseline were enrolled. Hepatitis B surface antigen (HBsAg) was tested using an on-site rapid test strip at baseline.

    Primary and secondary outcome measures Total and cause-specific mortality.

    Results A total of 35 822 deaths were recorded during ~10 years of follow-up. In multivariable-adjusted analyses, compared with HBsAg-negative participants, HBsAg-positive participants had an increased risk of total mortality (HR=2.01, 95% CI: 1.91 to 2.12), which was higher in men (HR=2.16, 95% CI: 2.01 to 2.31) than in women (HR=1.74, 95% CI: 1.60 to 1.90). Presence of HBsAg was associated with increased mortality from liver cancer (1339 deaths, HR=13.95, 95% CI: 12.46 to 15.62), infections (410 deaths, HR=10.30, 95% CI: 8.21 to 12.94), digestive diseases (688 deaths, HR=6.83, 95% CI: 5.49 to 8.50), intracerebral haemorrhage (4077 deaths, HR=1.38, 95% CI: 1.14 to 1.68) and ischaemic heart diseases (4624 deaths, HR=1.31, 95% CI: 1.09 to 1.58). The positive association between HBsAg status and risk of death was stronger in participants younger than 50 years, smokers, physically active or non-hypertensive participants.

    Conclusions Among Chinese adults, chronic HBV infection was associated with increased mortality from a range of hepatic and extrahepatic diseases.

    • chronic hepatitis B virus infection
    • mortality
    • stroke
    • ischaemic heart disease
    • prospective cohort study

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    • Contributors JLv and LL conceived and designed the paper. LL, ZC and JC, as the members of CKB Steering Committee, designed and supervised the conduct of the whole study, obtained funding, and together with YG, ZB, LY, YC, JJ, JLi and ZG acquired the data. JS and RM analyzed the data. JS drafted the manuscript. JLv, LL, CY, YG, ZB, RM, LY, YC, JJ, JLi, ZG, JC and ZC contributed to the interpretation of the results and critical revision of the manuscript for important intellectual content. All authors contributed to and approved the final manuscript.

    • Funding This work was supported by grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504 and 2016YFC1303904) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z and 104085/Z/14/Z), National Natural Science Foundation of China (81390540, 81390544 and 81390541) and Chinese Ministry of Science and Technology (2011BAI09B01).

    • Competing interests None declared.

    • Ethics approval Central ethics approvals were obtained from the Oxford Tropical Research Ethics Committee, University of Oxford (UK) and the Chinese Center for Disease Control and Prevention (Beijing, China). In addition, approvals were obtained from institutional research boards at the local Center for Disease Control and Prevention in the 10 regions.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Details of how to access China Kadoorie Biobank data and details of the data release schedule are available from

    • Collaborators International Steering Committee: JC, ZC (PI), Rory Collins, LL (PI), Richard Peto. International Co-ordinating Centre, Oxford: Daniel Avery, Ruth Boxall, Derrick Bennett, Yumei Chang, YC, ZC, Robert Clarke, Huaidong Du, Simon Gilbert, Alex Hacker, Michael Holmes, Andri Iona, Christiana Kartsonaki; Rene Kerosi, Ling Kong, Om Kurmi, Garry Lancaster, Sarah Lewington, Kuang Lin, John McDonnell, Winnie Mei, Iona Millwood, Qunhua Nie, Jayakrishnan Radhakrishnan, Sajjad Rafiq, Paul Ryder, Sam Sansome, Dan Schmidt, Paul Sherliker, Rajani Sohoni, Iain Turnbull, Robin Walters, Jenny Wang, Lin Wang, LY, Xiaoming Yang. National Co-ordinating Centre, Beijing: ZB, Ge Chen, YG, Can Hou, JLv, Pei Pei, Shuzhen Qu, Yunlong Tan, CY. 10 Regional Co-ordinating Centres: Qingdao CDC: Zengchang Pang, Ruqin Gao, Shaojie Wang, Yongmei Liu, Ranran Du, Yajing Zang, Liang Cheng, Xiaocao Tian, Hua Zhang. Licang CDC: Silu Lv, Junzheng Wang, Wei Hou. Heilongjiang Provincial CDC: Jiyuan Yin, Ge Jiang, Xue Zhou. Nangang CDC: Liqiu Yang, Hui He, Bo Yu, Yanjie Li, Huaiyi Mu, Qinai Xu, Meiling Dou, Jiaojiao Ren. Hainan Provincial CDC: Shanqing Wang, Ximin Hu, Hongmei Wang, Jinyan Chen, Yan Fu, Zhenwang Fu, Xiaohuan Wang. Meilan CDC: Min Weng, Xiangyang Zheng, Yilei Li, Huimei Li, Yanjun Wang. Jiangsu Provincial CDC: Ming Wu, Jinyi Zhou, Ran Tao, Jie Yang. Suzhou CDC: Chuanming Ni, Jun Zhang, Yihe Hu, Yan Lu, Liangcai Ma, Aiyu Tang, Shuo Zhang, JJ, JL. Guangxi Provincial CDC: Zhenzhu Tang, Naying Chen, Ying Huang. Liuzhou CDC: Mingqiang Li, Jinhuai Meng, Rong Pan, Qilian Jiang, Weiyuan Zhang, Yun Liu, Liuping Wei, Liyuan Zhou, Ningyu Chen, Hairong Guan. Sichuan Provincial CDC: Xianping Wu, Ningmei Zhang, Xiaofang Chen, Xuefeng Tang. Pengzhou CDC: Guojin Luo, Jianguo Li, Xiaofang Chen, Xunfu Zhong, Jiaqiu Liu, Qiang Sun. Gansu Provincial CDC: Pengfei Ge, Xiaolan Ren, Caixia Dong. Maiji CDC: Hui Zhang, Enke Mao, Xiaoping Wang, Tao Wang, Xi zhang. Henan Provincial CDC: Ding Zhang, Gang Zhou, Shixian Feng, Liang Chang, Lei Fan. Huixian CDC: Yulian Gao, Tianyou He, Huarong Sun, Pan He, Chen Hu, Qiannan Lv, Xukui Zhang. Zhejiang Provincial CDC: Min Yu, Ruying Hu, Hao Wang. Tongxiang CDC: Yijian Qian, Chunmei Wang, Kaixue Xie, Lingli Chen, Yidan Zhang, Dongxia Pan. Hunan Provincial CDC: Yuelong Huang, Biyun Chen, Li Yin, Donghui Jin, Huilin Liu, Zhongxi Fu, Qiaohua Xu. Liuyang CDC: Xin Xu, Hao Zhang, Youping Xiong, Huajun Long, Xianzhi Li, Libo Zhang, Zhe Qiu.

    • Patient consent for publication Not required.

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