广州地区HBV感染的家族聚集性及临床预后分析

Familial aggregation and clinical prognosis of hepatitis B virus infection in Guangzhou,China

目的对HBV感染高发区——广州地区慢性乙型肝炎（CHB）家族聚集流行特点及预后情况进行分析。方法收集2009年1月-2016年4月于中山大学附属第一医院肝炎门诊就诊的CHB患者,调查患者人口学基本特征、其亲属HBV标志物结果、患者HBV相关指标、肝脏生化指标及肝脏彩超、CT或磁共振成像。以至少2名具有亲缘关系成员诊断慢性HBV感染定义家族聚集,比较家族聚集组及非家族聚集组的临床特点。符合正态分布的计量资料组间采用t检验;不符合正态分布的采用Wilcoxon秩和检验。计数资料组间比较用χ^2检验或Fisher＇s精确概率法。单因素Logistic回归分析家族聚集方式与子代感染HBV、肝硬化及肝癌的发病风险。结果共1096例家族史明确的CHB患者纳入研究,家族史阳性者569例,即家族聚集率51.9%。按年龄划分为16-30岁,31-45岁和46岁以上分层分析,家族史阳性组与家族史阴性组3个年龄层诊断肝硬化的比例依次为2.1%、11.5%、35.6%和2.7%、5.7%、38.5%,家族史阳性组患者在31-45岁诊断肝硬化的比例明显高于家族史阴性组患者（χ^2=5.71,P=0.02）。聚集模式以同胞感染（30.2%）和母亲-子女感染（34.4%）最多见。父母均感染[比值比（OR）=8.18,95%可信区间（95%CI）：5.24-12.75]、母亲单方感染（OR=4.60,95%CI：3.69-5.74）和父亲单方感染（OR=2.77,95%CI：2.11-3.63）均与子代感染HBV有关,不同家族聚集模式并非患者发生肝硬化的危险因素（P〉0.05）,但父母均感染（OR=8.5,P〈0.01）可能是肝癌发生的危险因素。结论广州地区CHB感染具有高度家族聚集性,CHB家族史阳性患者可能更早发展为肝硬化。同胞感染和母亲-子女感染是最主要的家族聚集方式,家族聚集模式与子代感染HBV及肝癌发病相关。

Objective To investigate the characteristics of familial aggregation and prognosis of chronic hepatitis B（ CHB） in Guangzhou,China,where there is a high prevalence of hepatitis B virus（ HBV） infection. Methods The CHB patients who were treated in Outpatient Department of Hepatitis in the First Affiliated Hospital of Sun Yat- sen University from January 2009 to April 2016 were enrolled. The basic demographic features,relatives＇ HBV markers,patients＇ HBV indices,liver biochemical parameters,and findings on liver color Doppler ultrasound,computed tomography（ CT）,and magnetic resonance imaging（ MRI） were analyzed. Familial aggregation was defined as at least two relatives diagnosed with chronic HBV infection,and the clinical features were compared between the groups with and without familial aggregation. The t- test was used for comparison of normally distributed continuous data between groups,and the Wilcoxon rank sum test was used for non- normally distributed continuous data between groups. The chi- square test or Fisher＇ s exact test was used for comparison of categorical data between groups. The univariate logistic regression was used to analyze familial aggregation and the risk factors for HBV infection,liver cirrhosis,and liver cancer in offspring. Results A total of 1096 CHB patients with a clear family history were enrolled; among these patients,569 had a positive family history,resulting in a rate of familial aggregation of 51. 9%. According to their age,the patients were stratified into groups of 16- 30 years,31- 45 years,and 〉46 years. The proportions of patients diagnosed with liver cirrhosis across the three age stratifications in the groups with and without familial aggregation were 2. 1% /11. 5% /35. 6% and 2. 7% /5. 7% /38. 5%,respectively. The group with familial aggregation had a significantly higher proportion of patients aged 31- 45 years who were diagnosed with liver cirrhosis than the group without familial aggregation（ χ^2= 5. 71,P = 0. 02）. The familial aggregation pattern was dominated by infection between siblings（ 30. 2%） and mother- children infection（ 34. 4%）. Maternal and paternal infection（ OR = 8. 18,95% CI： 5. 24-12. 75）,maternal infection alone（ OR = 4. 60,95% CI： 3. 69- 5. 74）,and paternal infection alone（ OR = 2. 77,95% CI： 2. 11- 3. 63）were associated with HBV infection in offspring. Familial aggregation pattern was not the risk factor for the development of liver cirrhosis in patients（ P〉0. 05）,while maternal and paternal infection（ OR = 8. 5,P〈0. 01） was the risk factor for the development of liver cancer.Conclusion CHB infection shows high familial aggregation in Guangzhou,and the patients with a positive family history of CHB may progress to liver cirrhosis early.