1*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.
AbstractChronic 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.
1 *医学，香港大学玛丽医院，薄扶林道，内科，医学延世大学的香港†系，脑韩国21项目的医学科学，首尔，内科韩国‡教研室，台大医院，台北，台湾§Royal自由和大学学院，医学院，英国伦敦∥Hepatology单位和重点实验室器官功能衰竭的研究，南方医院，南方医科大学，广州，中国¶Southwestern医学中心，大学学院得克萨斯州，达拉斯，德克萨斯＃系统研究中心肝炎和免疫学，国家中心的全球健康和医学，市川，日本** INSERM UNITE 1052，里昂，里昂大学，法国里昂的癌症研究中心。
抽象
慢性乙型肝炎病毒（HBV）感染，从免疫耐受相的发展，通过免疫清除期到静止期或活化乙型肝炎e抗原阴性肝炎。持续性感染可能导致肝硬化和肝细胞癌（HCC）的发展。宿主因素，包括性别，年龄，家族史，HLA-DP和病毒因子，包括乙型肝炎病毒DNA，基因型，前核心突变，前S缺失和B型肝炎表面抗原（HBsAg）的水平与这些并发症的发展有关。肝癌发生的危险成绩一直而得。患者持续升高谷丙转氨酶水平（> 30为男性;> 19 U / L，女性）和HBV DNA水平> 2000 IU / mL的应及时治疗。患者具有可检测的HBV DNA建立肝硬化也应处理。推荐的一线药物包括聚乙二醇化干扰素和2核苷（酸）类似物，恩替卡韦和替诺福韦。来港需要长期治疗，以维持HBV DNA的抑制。它们已经显示出减少肝纤维化，或反向肝硬化和降低肝癌的发展。其电阻率很低（0％至1.2％）。乙肝表面抗原血清学清除，虽然理想的终点，只有10％实现到患者通过多中心临床试验通常学习比较年轻的患者12％。长期治疗的患者应为病毒突破，可能是由于不遵守或抗性的发展进行监测。较新的药物是根据试验，以提高的HBsAg血清清除率。然而，即使与当前NAS，> 6年的长期治疗可以显着地降低了共价闭合环状DNA，负责病毒复制的起始的病毒组分。