Genomics Research Center, Academia Sinica, Taipei, Taiwan; Department of Health Care Management, Chang-Gung University, Taoyuan City, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Clin Gastroenterol Hepatol. 2016 Sep;14(9):1347-1355.e4. doi: 10.1016/j.cgh.2016.03.043. Epub 2016 Apr 7.
BACKGROUND & AIMS: Arsenic in drinking water is associated with hepatomegaly and death from liver cancer. However, confounding factors related to liver diseases have not been carefully studied. We examined associations between exposure of arsenic in drinking water and risk of hepatitis and cirrhosis, and the interaction with chronic viral hepatitis, in people living in the Lanyang Basin of northeastern Taiwan, where well water has an arsenic content that ranges from undetectable to 3590 μg/L.
We tested blood samples from 4387 people who lived in arseniasis-endemic areas in northeastern Taiwan from 1991 through 1994 for hepatitis B virus DNA, hepatitis B surface antigen (HBsAg), and antibodies against hepatitis C virus (anti-HCV). We measured arsenic concentrations in well water and collected information on residents' histories of major chronic diseases. Reports of chronic hepatitis or cirrhosis were ascertained using the Taiwan National Health Insurance database. Reports of liver cancer were ascertained using the Taiwan National Cancer Registry.
Prevalence odds ratios in the overall study population for chronic hepatitis or cirrhosis for well water arsenic concentrations of ≤10 μg/L were 1.00 (reference), 0.93 for 10.1-49.9 μg/L (95% confidence interval [CI], 0.57-1.52), 1.24 for 50.0-99.9 μg/L (95% CI, 0.68-2.23), 0.98 for 100.0-299.9 (95% CI, 0.52-1.85), and 1.86 for ≥300.0 μg/L (95% CI, 1.08-3.20). Increasing levels of arsenic in drinking water were associated with increasing prevalence of chronic hepatitis or cirrhosis in residents who were seronegative for HBsAg and seronegative for anti-HCV, but not for seropositive for either HBsAg or anti-HCV. In individuals who were seropositive for HBsAg or anti-HCV, we observed an inverse association between hepatitis or cirrhosis and consumption of water with levels of arsenic ≥100.0 μg/L. Among participants who were seropositive for HBsAg or anti-HCV, consumption of water with levels of arsenic ≥100.0 μg/L was associated with a reduced risk of liver cancer (multivariate-adjusted hazard ratio, 0.29; 95% CI, 0.09-0.95; P < .05). A higher proportion of individuals exposed to cumulative arsenic level >14,000 μg/L ×year were carriers of inactive hepatitis B virus (DNA <10,000 copies/mL) and were positive for HBsAg (60%) than individuals exposed to water below this arsenic level (35%).
Concentrations of arsenic concentration in drinking water ≥300.0 μg/L significantly increase risk of hepatitis or cirrhosis in people without chronic viral hepatitis. However, in people with chronic viral hepatitis, levels of arsenic ≥100.0 μg/L in drinking water significantly reduce the risk of chronic hepatitis or cirrhosis.
饮用水中的砷与肝肿大和肝癌死亡有关。然而，与肝脏疾病相关的混杂因素尚未得到仔细研究。我们研究了台湾东北兰阳盆地居民饮用水中砷暴露与肝炎和肝硬化风险之间的关系，以及与慢性乙型肝炎病毒感染之间的相互作用，该盆地的井水砷含量从检测不到到 3590μg/L 不等。
我们检测了 1991 年至 1994 年间居住在台湾东北部砷污染地区的 4387 人的血样，以检测乙型肝炎病毒 DNA、乙型肝炎表面抗原（HBsAg）和丙型肝炎病毒抗体（抗 HCV）。我们测量了井水的砷浓度，并收集了居民主要慢性疾病史的信息。使用台湾国家健康保险数据库确定慢性肝炎或肝硬化的报告。使用台湾国家癌症登记处确定肝癌的报告。
在整个研究人群中，慢性肝炎或肝硬化的患病率比值（OR），对于砷浓度≤10μg/L 的井水为 1.00（参考），对于 10.1-49.9μg/L 的井水为 0.93（95%置信区间[CI]，0.57-1.52），对于 50.0-99.9μg/L 的井水为 1.24（95%CI，0.68-2.23），对于 100.0-299.9μg/L 的井水为 0.98（95%CI，0.52-1.85），对于≥300.0μg/L 的井水为 1.86（95%CI，1.08-3.20）。饮用砷浓度升高的井水与 HBsAg 阴性和抗 HCV 阴性的居民中慢性肝炎或肝硬化的患病率增加相关，但与 HBsAg 或抗 HCV 任一阳性的居民无关。在 HBsAg 或抗 HCV 阳性的个体中，我们观察到饮用水砷浓度≥100.0μg/L 与肝炎或肝硬化之间呈负相关。在 HBsAg 或抗 HCV 阳性的参与者中，饮用砷浓度≥100.0μg/L 与肝癌风险降低相关（多变量调整后的 HR，0.29；95%CI，0.09-0.95；P<0.05）。暴露于累积砷水平>14000μg/L×年的个体中，携带无活性乙型肝炎病毒（DNA<10000 拷贝/ml）和 HBsAg 阳性（60%）的比例高于暴露于该砷水平以下的个体（35%）。
饮用水中砷浓度≥300.0μg/L 显著增加无慢性病毒性肝炎人群发生肝炎或肝硬化的风险。然而，在患有慢性病毒性肝炎的人群中，饮用水中砷浓度≥100.0μg/L 可显著降低慢性肝炎或肝硬化的风险。
