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Environmental microcystin exposure increases liver injury risk induced by hepatitis B virus combined with aflatoxin: a cross-sectional study in Southwest China Wenyi Liu, Lingqiao Wang, Xiaohong Yang, Hui Zeng, Renping Zhang, Chaowen Pu, Chuanfen Zheng, Yao Tan, Yang Luo, Xiaobin Feng, Yingqiao Tian, Guosheng Xiao, Jia Wang, Yujing Huang, Jiaohua Luo, Lei Feng, Feng Wang, Changyou Yuan, Yuan Yao, Zhiqun Qiu, Ji-an Chen, Liping Wu, Qingqing Nong, Hui Lin, and Weiqun Shu Environ. Sci. Technol., Just Accepted Manuscript • Publication Date (Web): 03 May 2017 Downloaded from http://pubs.acs.org on May 8, 2017
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Chen, Ji-an; Third Military Medical University, Department of Health Education Wu, Liping; Third Military Medical University, Department of Environmental Hygiene Nong, Qingqing; Guangxi Medical University, Department of Environmental Health, School of Public Health Lin, Hui; Third Military Medical University, Department of Tropical Epidemiology Shu, Weiqun; Third Military Medical University, Department of Environmental Hygiene
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Title: Environmental microcystin exposure increases liver injury risk induced by hepatitis B virus combined with aflatoxin: a cross-sectional study in Southwest China Wenyi Liu1, Lingqiao Wang1, Xiaohong Yang1, Hui Zeng1, Renping Zhang2, Chaowen Pu2, Chuanfen Zheng1, Yao Tan1, Yang Luo3, Xiaobin Feng4, Yingqiao Tian2, Guosheng Xiao5, Jia Wang1, Yujing Huang1, Jiaohua Luo1, Lei Feng2, Feng Wang6, Changyou Yuan7, Yuan Yao1, Zhiqun Qiu1, Ji-an Chen8, Liping Wu1, Qingqing Nong9, Hui Lin10*, and Weiqun Shu1* 1
Department of Environmental Hygiene, College of Preventive Medicine, Third Military
Medical University, Chongqing, 400038, China; 2The Center for Disease Control and Prevention in Fuling District, Chongqing, 408000, China; 3Department of Transfusion Medicine, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China; 4Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China; 5College of Life Science and Engineering, Chongqing Three Gorges University, Wanzhou, Chongqing, 404100, China; 6The Township Central Hospital in Yihe Town, Fuling District, Chongqing, 408104, China; 7The Community Health Service Center in Lidu Town, Fuling District, Chongqing, 408103, China; 8Department of Health Education, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China; 9Department of Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China; 10
Department of Tropical Epidemiology, College of Preventive Medicine, Third Military
Medical University, Chongqing, 400038, China.
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Corresponding author:
Weiqun Shu*. Department of Environmental Hygiene, College of Preventive Medicine, Third Military Medical University, Chongqing, China. Telephone: 86-23-68772309. E-mail:
[email protected].
Hui Lin*. Department of Tropical Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, China. Telephone: 86-13637960337. E-mail:
[email protected]. Running title: HBV, AFB and MC exposure as risks of liver injury
Disclosures: All authors declare no conflict of interest.
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Abstract
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Three liver hazards, two confirmed—hepatitis B virus (HBV) and aflatoxin (AFB), and one
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rarely studied in populations—microcystin (MC), simultaneously exist in tropical and humid
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areas; however, there are no epidemiological data on their risks in a same population. We
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conducted a community-based cross-sectional survey among 5493 adults in two rural towns,
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and statistically analyzed the comparative and combinative effects of the three factors after
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detecting HBsAg and HBV DNA titres, determining estimated daily intakes (EDIs) of AFB1
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and MC-LR, and testing serum AST and ALT as liver injury markers for each participant.
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We observed a HBsAg(+) rate of 7.6%, a relatively high AFB1 exposure level (mean
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EDIAFB1=471.30 ng/d), and a relatively low MC-LR exposure level (mean EDIMC-LR=228.25
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ng/d). ORs for abnormal AST (2.42, 95%CI=1.69-3.45) and ALT (2.87, 95%CI=1.91-4.29)
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increased in HBV-infections compared with HBV-unexposed participants, but not increased
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in participants with separate or combined exposure to AFB1 and MC-LR (EDIs≥mean).
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Meanwhile, after adjustment for confounding factors, means of AST and ALT and ORs of
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abnormal AST and ALT were successively elevated after exposure to HBV, HBV&AFB1 (or
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HBV&MC-LR), and HBV&AFB1&MC-LR, especially in group with detectable HBV DNA
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(AST: OR=11.38, 95%CI=3.91-33.17; ALT: OR=17.09, 95%CI=5.36-54.53). Notably, ORs
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for abnormal AST and ALT in HBV exposed group were not significantly different with
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those in HBV&AFB1 or in HBV&MC-LR exposed group, but were significantly higher in
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HBV&AFB1&MC-LR exposed group (P=0.029 and P=0.037, respectively). Our study
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indicated that microcystin may have the potential to increase the risk of liver injury induced
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by combined exposure to HBV and aflatoxin. However, in consideration of the uncertainties
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in the detection of the toxins and evaluation of the EDIs, more epidemiological data are
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expected to determine the increasing toxic effects of microcystins.
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Introduction
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Liver injury is linked with numerous adverse outcomes, such as hepatitis fibrosis, cirrhosis,
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hepatocellular carcinoma (HCC), hepatic encephalopathy, hepatic failure and even death. The
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risk factors for liver injury include chronic virus infection, environmental toxin exposure,
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alcohol drinking, smoking, overweight, and diabetes. Among them, hepatitis B virus (HBV),
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aflatoxins (AFBs) and microcystins (MCs) are three major risk factors that generally and
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simultaneously exist in tropical and humid areas, especially in developing countries.
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WHO reported (updated in July 2016) that approximately 240 million people have been
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chronically infected with HBV—a major liver injury burden—all over the world. On the
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basis of the prevalence of HBV infection, areas of the high (prevalence: 5~10%), the
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intermediate (prevalence: 2~5%), and the low (prevalence:
