Long-term Outcome of Hepatitis B e Antigen-Negative Hepatitis B Surface Antigen Carriers in Relation to Changes of Alanine Aminotransferase Levels Over Time
Long-term Outcome of Hepatitis B e Antigen-Negative Hepatitis B Surface Antigen Carriers in Relation to Changes of Alanine Aminotransferase Levels Over Time
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DOI：
10.1002/hep.22878
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发表时间：
2009-06-01
期刊：
影响因子：
13.5
通讯作者：
Liaw, Yun-Fan
中科院分区：
文献类型：
--
作者：
Tai, Dar-In;Lin, Shi-Ming;Liaw, Yun-Fan
基线丙氨酸氨基转移酶(ALT)水平被报道对慢性乙肝病毒(HBV)感染有预后价值，在此期间ALT可能会随着时间的推移而改变。本研究旨在研究慢性乙肝病程中ALT升高的预后价值，而不是基线ALT。对4376例基础ALT低于正常值上限2倍的无症状乙肝e抗原(HBeAg)阴性、表面抗原(HBs)携带者，每3~12个月进行一次ALT检测和超声检查，连续监测3年以上。使用来自医院记录、癌症登记和国家死亡率数据库的发病率和死亡率数据，追踪期间的最大ALT水平与长期结果相关。在平均13.4+/-5.2(3.0-28.7)年的随访期内，3673名受试者的基础ALT水平正常，其中1720人(46.8%)上升至异常水平。与ALT正常者相比，随最大ALT水平升高，肝硬变、肝细胞癌的发生率和死亡率增加，尤其是最大ALT至少为ULN的2倍者。COX回归分析显示，入院年龄、性别和随访期间最大ALT水平是与肝硬变、肝细胞癌和死亡率相关的显著独立因素，而肝硬变也是肝细胞癌发生和死亡的独立因素。结论：ALT持续正常与良好的长期预后相关，而在随访期间ALT水平升高至少2倍ULN与发病率和死亡率增加相关。因此，ALT至少是ULN的2倍是抗乙肝治疗的合适阈值，而ALT 1-2倍ULN的患者需要肝脏活检才能做出决定。(《肝病》2009；49：1859-1867。)
The baseline alanine aminotransferase (ALT) level was reported to have prognostic value in chronic hepatitis B virus (HBV) infection, during which ALT may change over time. Instead of baseline ALT, this study aimed to study the prognostic value of the height of ALT during the course of chronic HBV infection. A total of 4376 asymptomatic hepatitis B e antigen (HBeAg) negative, surface antigen (HBsAg) carriers with baseline ALT less than 2 times the upper limit of normal (ULN) were monitored with ALT measurement and ultrasonography every 3 to 12 month for over 3 years. Maximal ALT levels during follow-up were correlated with long-term outcomes using morbidity and mortality data from hospital records, cancer registration, and national mortality database. Baseline ALT level was normal in 3673 subjects and increased to abnormal level in 1720 (46.8%) during a mean follow-up period of 13.4 +/- 5.2 (3.0-28.7) years. The incidence of liver cirrhosis, hepatocellular carcinoma (HCC), and mortality increased with increasing maximal ALT level during follow-up, especially in those with maximal ALT of at least 2 times ULN, as compared with those who maintained normal ALT. Cox regression analysis indicated that age at entry, sex, and maximal ALT level during follow-up were significant independent factors associated with the development of cirrhosis, HCC, and mortality whereas cirrhosis was also an independent factor for HCC development and mortality. Conclusion: Persistently normal ALT was associated with excellent long-term prognosis, whereas increasing ALT levels of at least 2 times ULN during follow-up was associated with increasing morbidity and mortality. ALT of at least 2 times ULN is therefore an appropriate threshold for anti-HBV therapy, whereas those with ALT 1 to 2 times ULN require liver biopsy for decision. (HEPATOLOGY 2009;49: 1859-1867.)