Berenguer M, Wright T L
Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
Proc Assoc Am Physicians. 1998 Mar-Apr;110(2):98-112.
Four agents are in clinical development for the treatment of chronic hepatitis B infection. These nucleoside analogs are incorporated into the growing DNA chain and terminate replication. Lamivudine, a cytadine analog that inhibits the synthesis of negative strand DNA from pre-genomic RNA, predictably inhibits replication and improves liver enzymes and histology in infected individuals. Following cessation of treatment, relapse is common, and genetic causes of viral resistance have been described. Other drugs for HBV infection include famciclovir, a guanosine analog that has also shown to suppress replication in immunocompetent as well as in immunocompromised patients; lobucavir, a guanosine analog; and adevfovir, an adenine nucleotide analog. The future of drug therapy against HBV likely includes combination agents with one or more nucleoside/nucleotide analogs and immune stimulants, such as interferon, or therapeutic vaccines. Recent advances in the treatment of HCV have been less impressive. An effective vaccine is greatly needed yet development in the near future is unlikely. Recommendations for therapy of chronic HCV have been proposed following the National Institutes of Health Consensus Conference. Interferon alpha is advised in patients with elevated serum alanine aminotransferases and liver histology demonstrating active hepatitis, regardless of level of pretreatment viremia or infecting genotype. Therapy should be continued for three months, at which time response should be assessed. If a biochemical and/or virological response has been achieved, treatment should be continued for a year. Trials are underway to evaluate interferon in combination with ribavirin. Recent identification of the crystalline structure of the HCV NS3 protease promises development of effective inhibitors of this critical viral enzyme.
有四种药物正在进行治疗慢性乙型肝炎感染的临床试验。这些核苷类似物会掺入正在延长的DNA链中并终止复制。拉米夫定是一种胞苷类似物，可抑制前基因组RNA合成负链DNA，可预期地抑制感染个体的病毒复制并改善肝酶和组织学情况。治疗停止后，复发很常见，并且已经描述了病毒耐药的遗传原因。其他用于治疗乙肝病毒感染的药物包括泛昔洛韦，一种鸟苷类似物，在免疫功能正常以及免疫功能低下的患者中均显示出抑制病毒复制的作用；洛布卡韦，一种鸟苷类似物；以及阿德福韦，一种腺嘌呤核苷酸类似物。抗乙肝病毒药物治疗的未来可能包括将一种或多种核苷/核苷酸类似物与免疫刺激剂（如干扰素）或治疗性疫苗联合使用。丙型肝炎治疗的最新进展则不太显著。目前非常需要一种有效的疫苗，但近期不太可能研制出来。美国国立卫生研究院共识会议之后提出了慢性丙型肝炎的治疗建议。对于血清丙氨酸氨基转移酶升高且肝组织学显示有活动性肝炎的患者，建议使用α干扰素，无论治疗前病毒血症水平或感染基因型如何。治疗应持续三个月，届时应评估疗效。如果已实现生化和/或病毒学应答，则治疗应持续一年。正在进行试验以评估干扰素与利巴韦林联合使用的效果。最近对丙型肝炎病毒NS3蛋白酶晶体结构的鉴定有望开发出针对这种关键病毒酶的有效抑制剂。
