Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taichung, Taiwan.
J Gastroenterol Hepatol. 2011 Apr;26(4):628-38. doi: 10.1111/j.1440-1746.2011.06695.x.
Chronic hepatitis B is a worldwide public health challenge. Knowledge of natural history of chronic hepatitis B is important for the management of the disease. A community-based prospective cohort study was carried out to evaluate the risk predictors of progression of chronic hepatitis B in Taiwan. A total of 23,820 participants were enrolled in 1991-1992 from seven townships in Taiwan. Their serum samples were collected at study entry and tested for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), antibodies against hepatitis C virus (anti-HCV), alanine aminotransferase (ALT), and α-fetoprotein (AFP). A subcohort of 3653 male and female participants who were seropositive for HBsAg and seronegative for anti-HCV was included in the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study. Newly developed cases of cirrhosis and hepatocellular carcinoma (HCC) were ascertained through follow-up examination and data linkage with profiles of the National Cancer Registry, National Health Insurance Database and Death Certification System. The incidence of both HCC and cirrhosis were significantly associated with serum HBV DNA levels in a dose-response relationship from <300 (undetectable) to ≥1,000,000 copies/mL. The biological gradients remained significant (P<0.001) after adjustment for age, sex, habits of cigarette smoking and alcohol drinking, HBeAg serostatus, and serum ALT level at cohort entry. A significant association with risk of cirrhosis and HCC was also observed for HBV genotype, precore G1896A mutant and basal core promoter A1762T/G1764A double mutant. Nomograms have been developed for the long-term risk prediction of cirrhosis and HCC for patients with chronic hepatitis B. Inactive carriers of HBV have an increased HCC incidence and liver-related mortality than HBsAg-seronegative controls. Serum HBV DNA level at study entry is a major predictor of spontaneous seroclearance of HBeAg, HBV DNA and HBsAg. These findings may inform the effective and efficient management of chronic hepatitis B.
慢性乙型肝炎是全球性的公共卫生挑战。了解慢性乙型肝炎的自然史对于该病的管理非常重要。本研究开展了一项基于社区的前瞻性队列研究，以评估台湾慢性乙型肝炎进展的风险预测因素。1991 年至 1992 年，研究人员从台湾的 7 个乡镇招募了 23820 名参与者。在研究入组时收集了他们的血清样本，用于检测乙型肝炎表面抗原 (HBsAg) 和 e 抗原 (HBeAg)、丙型肝炎病毒抗体 (抗-HCV)、丙氨酸氨基转移酶 (ALT) 和甲胎蛋白 (AFP)。在该队列中，纳入了 3653 名男性和女性 HBsAg 血清学阳性和抗-HCV 血清学阴性的亚组，以开展病毒载量升高和相关肝病/肝癌-乙型肝炎病毒（REVEAL-HBV）研究。通过随访检查和与国家癌症登记处、国家健康保险数据库和死亡证明系统的资料进行关联，确定新发生的肝硬化和肝细胞癌 (HCC)病例。结果发现，HBV DNA 血清水平与 HCC 和肝硬化的发生率呈剂量反应关系，从 <300（检测不到）至≥1,000,000 拷贝/mL。在校正年龄、性别、吸烟和饮酒习惯、HBeAg 血清状态以及队列入组时的血清 ALT 水平后，这种生物学梯度仍然具有显著意义（P<0.001）。还观察到 HBV 基因型、前核心 G1896A 突变和基本核心启动子 A1762T/G1764A 双突变与肝硬化和 HCC 风险之间存在显著相关性。为慢性乙型肝炎患者开发了用于预测肝硬化和 HCC 的长期风险的列线图。HBV 不活动携带者的 HCC 发生率和肝脏相关死亡率高于 HBsAg 血清学阴性对照者。研究入组时的 HBV DNA 血清水平是自发清除 HBeAg、HBV DNA 和 HBsAg 的主要预测因素。这些发现可能为慢性乙型肝炎的有效和高效管理提供信息。
