Hanazaki Kazuhiro
Division of Gastroenterological Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):63-70. doi: 10.2174/1568010043483908.
Chronic hepatitis B virus (HBV) infection is a well-recognized risk factor for the development of hepatocellular carcinoma (HCC), which is becoming a more prevalent clinical problem, especially in HBV-endemic areas. It is estimated that 1.25 million people in the United States and more than 300 million people worldwide are chronically infected with HBV. Despite the introduction of universal vaccination against hepatitis B in over 100 countries, persistent HBV infection is still a serious problem worldwide, causing an estimated annual death rate of one million. It may take several decades until the effect of vaccination will be translated into reduced transmission and morbidity. Meanwhile, patients with persistent HBV infection require better antiviral therapeutic modalities than are currently available. It is well accepted that antiviral therapy for chronic hepatitis B is effective to improve prognosis of patients with HBV by preventing development of hepatitis state and HCC. The therapeutic endpoints for hepatitis B treatment are: 1) sustained suppression of HBV replication, as indicated by HBsAg and HBeAg loss, 2) decrease of serum HBV DNA of an undetectable level by a non-PCR method, 3) remission of disease, as shown by normalization of ALT, 4) improvement in liver histology, and 5) reduction of the acute exacerbation, cirrhosis, and HCC. In the present, the antiviral treatment of hepatitis B consists of either interferon alpha or oral lamivudine alone or in combination with existing therapy. Each major antiviral drug of interferon alpha and lamivudine has pros and cons, and effect of combination therapy of both drugs is also still limited. More powerful and safe new antiviral therapies are required to achieve final goal of these therapeutic endpoints. Management of chronic hepatitis B requires significant knowledge of approved pharmacotherapeutic agents and their limitations. Therapeutic options for managing hepatitis infection after liver transplantation (LT) are also evolving.
慢性乙型肝炎病毒(HBV)感染是肝细胞癌(HCC)发生的一个公认危险因素,HCC正成为一个日益普遍的临床问题,尤其是在HBV流行地区。据估计,美国有125万人、全球有超过3亿人慢性感染HBV。尽管100多个国家已推行乙肝普遍疫苗接种,但HBV持续感染在全球仍是一个严重问题,估计每年导致100万人死亡。可能需要几十年时间,疫苗接种的效果才能转化为传播率降低和发病率下降。与此同时,持续HBV感染患者需要比现有治疗方法更好的抗病毒治疗方式。慢性乙型肝炎的抗病毒治疗可有效改善HBV患者的预后,预防肝炎状态和HCC的发生,这一点已得到广泛认可。乙型肝炎治疗的终点包括:1)持续抑制HBV复制,表现为HBsAg和HBeAg消失;2)通过非PCR方法使血清HBV DNA降至不可检测水平;3)疾病缓解,表现为ALT正常化;4)肝脏组织学改善;5)急性加重、肝硬化和HCC发生率降低。目前,乙型肝炎的抗病毒治疗包括单独使用干扰素α或口服拉米夫定,或与现有疗法联合使用。干扰素α和拉米夫定这两种主要抗病毒药物各有优缺点,两种药物联合治疗的效果也仍然有限。需要更强大、更安全的新型抗病毒疗法来实现这些治疗终点的最终目标。慢性乙型肝炎的管理需要对已批准的药物治疗剂及其局限性有充分了解。肝移植(LT)后肝炎感染的治疗选择也在不断发展。