Yuen Man-Fung, Ahn Sang Hoon, Chen Ding-Shinn, Chen Pei-Jer, Dusheiko Geoffrey M, Hou Jin-Lin, Maddrey Willis C, Mizokami Masashi, Seto Wai-Kay, Zoulim Fabien, Lai Ching-Lung
*Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong†Department of Internal Medicine, Yonsei University College of Medicine, Brain Korea 21 Project for Medical Science, Seoul, South Korea‡Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan§Royal Free and University College, School of Medicine, London, UK∥Hepatology Unit and Key Laboratory for Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China¶Southwestern Medical Center, University of Texas, Dallas, TX#The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan**INSERM Unité 1052, Cancer Research Center of Lyon, Lyon University, Lyon, France.
J Clin Gastroenterol. 2016 Apr;50(4):286-94. doi: 10.1097/MCG.0000000000000478.
Chronic hepatitis B virus (HBV) infection evolves from immune-tolerance phase, through immune clearance phase to a quiescent phase or reactivation as hepatitis B e antigen-negative hepatitis. Persistent infection may result in the development of cirrhosis and hepatocellular carcinoma (HCC). Host factors including gender, age, family history, HLA-DP, and viral factors including HBV DNA, genotypes, precore mutations, pre-S deletions, and hepatitis B surface antigen (HBsAg) level are associated with the development of these complications. Risk scores for the development of HCC have been derived. Patients with persistently elevated alanine aminotransferase levels (>30 for males; >19 U/L for females) and HBV DNA levels >2000 IU/mL should be treated. Patients with established cirrhosis with detectable HBV DNA should also be treated. The recommended first-line agents include pegylated interferon and 2 nucleos(t)ide analogs, entecavir and tenofovir. NAs require long-term treatment to maintain suppression of HBV DNA. They have been shown to decrease hepatic fibrosis, or reverse cirrhosis and to reduce the development of HCC. They have very low rates (0% to 1.2%) of resistance. HBsAg seroclearance, although the ideal endpoint, is only achievable in 10% to 12% of patients by multicenter trials usually studying relatively young patients. Patients on long-term treatment should be monitored for viral breakthrough that may be due to noncompliance or the development of resistance. Newer agents are under trials to enhance the rate of HBsAg seroclearance. However, even with the current NAs, long-term treatment of >6 years can markedly reduce the covalently closed circular DNA, the viral component responsible for initiation of viral replication.
慢性乙型肝炎病毒（HBV）感染从免疫耐受期开始，经过免疫清除期发展至静止期，或重新激活为e抗原阴性肝炎。持续感染可能导致肝硬化和肝细胞癌（HCC）的发生。宿主因素包括性别、年龄、家族史、HLA - DP，病毒因素包括HBV DNA、基因型、前核心突变、前S区缺失以及乙肝表面抗原（HBsAg）水平，均与这些并发症的发生相关。已经得出了HCC发生的风险评分。丙氨酸氨基转移酶水平持续升高（男性>30 U/L；女性>19 U/L）且HBV DNA水平>2000 IU/mL的患者应接受治疗。已确诊肝硬化且可检测到HBV DNA的患者也应接受治疗。推荐的一线药物包括聚乙二醇化干扰素和两种核苷（酸）类似物，即恩替卡韦和替诺福韦。核苷（酸）类似物需要长期治疗以维持对HBV DNA的抑制。已证明它们可减少肝纤维化，或逆转肝硬化并降低HCC的发生。它们的耐药率非常低（0%至1.2%）。HBsAg血清学清除虽是理想的终点，但在多中心试验中通常研究相对年轻的患者，只有10%至12%的患者能够实现。长期治疗的患者应监测可能由于不依从或耐药发生导致的病毒突破。新型药物正在进行试验以提高HBsAg血清学清除率。然而，即使使用目前的核苷（酸）类似物，>6年的长期治疗也可显著减少共价闭合环状DNA，即负责启动病毒复制的病毒成分。
