Leemans W F, Janssen H L A, de Man R A
Department of Gastroenterology and Hepatology, Room H 437, Erasmus MC, University Medical Center Rotterdam's-Gravendijkwal 230, Rotterdam, The Netherlands.
World J Gastroenterol. 2007 May 14;13(18):2554-67. doi: 10.3748/wjg.v13.i18.2554.
Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately a million deaths a year. Since the discovery of interferon-alpha as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load (HBV-DNA) plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory (interferons) and antiviral suppressants (nucleoside and nucleotide analogues) all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log(10) is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross-resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely.
chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determine the best treatment for those failing treatment.
慢性乙型肝炎病毒感染影响全球约4亿人，每年导致约100万人死亡。自发现α干扰素作为一种治疗选择以来，乙型肝炎的治疗发展迅速，管理也变得越来越复杂。病毒载量（HBV-DNA）所反映的病毒复制量在肝硬化和肝细胞癌的发生发展中起重要作用。慢性乙型肝炎的当前治疗方式包括免疫调节药物（干扰素）和抗病毒抑制剂（核苷和核苷酸类似物），它们都有各自的优点和局限性。本文概述了免疫调节药物和抗病毒药物的治疗效果，以便为临床医生提供影响治疗结果的因素的见解。使用核苷或核苷酸类似物可将病毒复制抑制5-7个对数（10），但并非所有患者都对治疗有反应。已知影响治疗结果的因素有病毒载量、ALT水平和依从性。许多其他可能影响治疗的因素几乎未被研究。识别与反应相关的因素可能会产生停药规则，这样治疗可以在早期进行调整，以提供充分的治疗并避免耐药性的产生。治疗突变病毒和交叉耐药的化合物的疗效在很大程度上尚不清楚。然而，基因分型和表型检测以及小型临床试验提供了一些关于该人群疗效的数据。停用核苷或核苷酸类似物经常会导致病毒复发；然而，一些患者有持续反应。为了确定何时可以安全停药，需要有关复发危险因素的数据。
慢性乙型肝炎已成为一种可治疗的疾病；然而，需要进行大量研究，以便为个体患者量身定制治疗方案，预测反应的可持续性，并确定对治疗失败患者的最佳治疗方法。
