血清乙型肝炎病毒DNA阳性与原发性肝癌危险性关系的前瞻性队列研究

A prospective study of the relationship between serum hepatitis B virus DNA and the risk of primary liver cancer

目的探讨血清HBV DNA阳性与原发性肝癌的关系。方法以分层抽样方法对广西隆安县12个乡镇30～55岁农村居民抽样，采静脉血，酶联免疫吸附试验检测HBsAg，套式聚合酶链反应检测HBV DNA。根据HBsAg和DNA检测结果，将研究对象分为HBsAg（＋）／HBvDNA（＋）组（A组）和HBsAg（＋）／HBVDNA（-）组（B组）；根据1：1匹配原则，从本村屯HBsAg（-）者中为前两组观察对象挑选对照，组成HBsAg阴性对照组（C组），对这3组人群进行4年的前瞻性跟踪随访。卡方检验对各组及各因素的发病率进行统计分析，然后用Cox比例风险模型分析与PLC有关的危险因素，用后退法对数值进行迭代分析。结果30～55岁人群HBsAg阳性率为14．52％（3975／27379），HBsAg阳性者HBV DNA阳性率为40．35％（1604／3975）。A、B两组总的肝癌发病率为672．45／10万人年，明显高于C组的17．19／10万人年（P〈0．01），相对危险度为39．123，95％可信因司为9．018～159．146。A组肝癌发病率为984．03／10万人年，显明高于C组的324．38／10万人年（P〈0．01），相对危险度为3．034，95％可信区间为1．795～5．125。对A、B两组进行肝癌危险因素的多因素Cox模型分析，结果表明性别、年龄、血清HBV DNA阳性、肝癌家族史和以玉米为主食均为肝癌的危险因素。结论血清HBV DNA阳性可增加HBsAg阳性者的肝癌危险性。

Objective To determine the relationship between the serum hepatitis B virus （HBV） DNA and the risk of primary liver cancer （PLC）. Methods Farmers aged 30-55 years in Long An county were recruited in this study Blood samples were collected and the sera were tested for HBsAg using Enzyme- Linked ImmunoSorbent Assay （ELISA）, and the HBsAg-positive sera were further tested for viral DNA using nested polymerase chain reaction （nPCR）. The study subjects were divided into three groups. The first group was positive for both HBsAg and HBV DNA. The second group was positive for HBsAg but negative for HBV DNA. Age-, sex-, residence-matched HBsAg negative controls for group 1 and group 2 were enrolled in the third group. The cohort was followed up for four years. Results The positive rate of HBsAg in these farmers was 14.52% （3975/27 379）, and the HBV DNA positive rate in HBsAg positive subjects was 40.35% （1604/3975）. The total PLC incidence rate in Group 1 and 2 was 672.45/100 000 person-years （PY）, significantly higher than that in Group3 （17.19/100 000 PY）. The relative risk （RR） was 39.123, and the 95% confidence interval （CI） was 9.018-159.146. The PLC incidence rate of Group 1 （984.03/100 000 PY） was significantly higher than that of Group2 （324.38/100 000 PY）. The RR was 3.034, and the 95% CI was 1.795-5.125. Multivariate analyses of Groupl and 2 with Cox model showed that sex, age, serum HBV DNA, and family history of PLC were independent risk factors of PLC. Conclusion HBV DNA and HBsAg positive subjects have a higher chance to develop PLC than HBV DNA negative-, HBsAg positive subjects.