Liaw Yun-Fan
Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
Liver Int. 2009 Jan;29 Suppl 1:100-7. doi: 10.1111/j.1478-3231.2008.01941.x.
Chronic hepatitis B virus (HBV) infection is a dynamic state of interactions among HBV, the hepatocytes and the immune system of the patient. Perinatally or early childhood-acquired chronic HBV infection has a long 'immune tolerant phase', when patients are young, and HBeAg seropositive with a high viral load but with no significant liver disease. Persistent or episodic liver injuries during the 'immune clearance phase' may lead to decompensation, fibrosis progression or cirrhosis development in some patients, but may eventually lead to HBV-DNA seroclearance with HBeAg seroconversion and entry into the 'inactive phase' with remission. Hepatitis may relapse, because of reactivation of HBV with precore or basal core promptor mutations, and develop 'HBeAg-negative chronic hepatitis', in some patients. In contrast, HBsAg seroclearance may occur in those with sustained remission. During the course, HBV replication is the key driver of disease progression including development of cirrhosis and hepatocellular carcinoma (HCC). Among the currently available anti-HBV drugs, the most extensive and longest experience has been gained with conventional interferon (IFN)-alpha and lamivudine. A finite course of IFN therapy has long-term benefit in achieving a cumulative response, increasing HBsAg seroclearance and reducing cirrhosis and/or HCC. Maintained virological response to lamivudine therapy has a similar long-term benefit in reducing disease progression. Pegylated IFN and newer nucleos(t)ide analogues may have even better long-term outcomes because of better therapeutic efficacy and/or a low risk of drug resistances. The treatment outcomes are still far from satisfactory. The development of safe and affordable anti-HBV agents/strategies is needed to further improve outcomes.
慢性乙型肝炎病毒（HBV）感染是HBV、肝细胞和患者免疫系统之间相互作用的动态状态。围产期或儿童早期获得的慢性HBV感染有一个漫长的“免疫耐受期”，此时患者年轻，HBeAg血清学阳性，病毒载量高，但无明显肝脏疾病。在“免疫清除期”持续或间歇性的肝损伤可能导致一些患者出现失代偿、纤维化进展或肝硬化，但最终可能导致HBV-DNA血清清除、HBeAg血清学转换并进入“非活动期”且病情缓解。在一些患者中，由于前核心或基础核心启动子突变导致HBV重新激活，肝炎可能复发，并发展为“HBeAg阴性慢性肝炎”。相比之下，在病情持续缓解的患者中可能会出现HBsAg血清清除。在这个过程中，HBV复制是疾病进展的关键驱动因素，包括肝硬化和肝细胞癌（HCC）的发生。在目前可用的抗HBV药物中，传统干扰素（IFN）-α和拉米夫定的应用经验最为广泛和悠久。有限疗程的IFN治疗在实现累积应答、增加HBsAg血清清除以及减少肝硬化和/或HCC方面具有长期益处。对拉米夫定治疗保持病毒学应答在减少疾病进展方面具有类似的长期益处。聚乙二醇化干扰素和新型核苷（酸）类似物可能由于更好的治疗效果和/或较低的耐药风险而具有更好的长期疗效。然而，治疗结果仍远不能令人满意。需要开发安全且价格可承受的抗HBV药物/策略以进一步改善治疗效果。
