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[慢性乙型肝炎的跨学科研究进展与新型药物]

[Interdisciplinary aspects of and new drugs for chronic hepatitis B].

作者信息

Horváth Gábor

机构信息

Budai Hepatológiai Centrum Budapest Királyhágó.

出版信息

Orv Hetil. 2013 Jul 21;154(29):1142-50. doi: 10.1556/OH.2013.29625.

Abstract

Hepatitis B virus infection is a significant health problem worldwide. The prevalence of HBsAg positivity is about 0.5-0.7% in Hungary. Liver cirrhosis and/or hepatocellular carcinoma develops in 15-40% of chronic hepatitis B virus infected patients without treatment. The ultimate goal of treatment would be to clear the virus from the infected subject; however, in practice, we can usually achieve long term suppression of viral replicaton with consequent prevention of the progression of liver disease, and reduction of the risk of the development of liver cirrhosis and hepatocellular carcinoma. Currently, there are two different treatment strategies for patients with chronic hepatitis B virus infection: therapy of finite duration with interferon or long-term treatment with nucleot(s)ide analogues. Entecavir and tenofovir are the two most effective nucleot(s)ide analogues with high barrier to resistance, thus, they can be confidently used as first-line treatments. Lamivudine engenders very high rates of resistance; adefovir is less efficacious than entecavir or tenofovir, and also engendering higher rates of resistance, thus none of them are recommended for initiation of a new treatment. Tenofovir is the treatment option in cases with lamivudine resistance, because entecavir has an unfavourable resistance-profile in this group of patients. Interferon is contraindicated during pregnancy. Should treatment of chronic hepatitis B virus infection be necessary during pregnancy, tenofovir, listed by the FDA as pregnancy category B drug, is to be preferred. Nucleot(s)ide analogues may be used to reduce the risk of intra-uterine and perinatal transmission of hepatitis B virus, which may occur in a proportion of newborns from highly viremic mothers, despite active and passive immunization. Similarly, tenofovir is recommended in the last trimester of pregnancy for women with high viremia. The risk of reactivation of chronic hepatitis B virus infection is high in HBsAg positive patients, and in patients with occult hepatitis B virus infection during and after chemotherapy or immunosuppressive treatment, including biological response modifiers (particularly related to rituximab therapy). Therefore, all candidates for these treatments should be screened for HBsAg and anti-HBc. Pre-emptive nucleot(s)ide analogues therapy should be initiated in patients with HBsAg positivity, and patients with occult hepatitis B virus infection. The role of general practitioners and occupational health physicians in the identification and the prevention of hepatitis B virus infection is stressed. Issues of high risk population groups, candidacy for vaccination, and methodology of active and passive immunisation are also reviewed in this paper.

摘要

乙肝病毒感染是全球一个重大的健康问题。在匈牙利,乙肝表面抗原(HBsAg)阳性率约为0.5 - 0.7%。未经治疗的慢性乙肝病毒感染患者中,15 - 40%会发展为肝硬化和/或肝细胞癌。治疗的最终目标是清除感染个体体内的病毒;然而,在实际中,我们通常能够实现长期抑制病毒复制,从而预防肝病进展,并降低肝硬化和肝细胞癌发生的风险。目前,对于慢性乙肝病毒感染患者有两种不同的治疗策略:用干扰素进行有限疗程治疗或用核苷(酸)类似物进行长期治疗。恩替卡韦和替诺福韦是两种最有效的核苷(酸)类似物,耐药性高,因此可放心用作一线治疗药物。拉米夫定耐药率极高;阿德福韦的疗效低于恩替卡韦或替诺福韦,且耐药率也较高,因此均不建议用于开始新的治疗。对于拉米夫定耐药的病例,替诺福韦是治疗选择,因为恩替卡韦在这类患者中的耐药情况不佳。孕期禁用干扰素。如果孕期有必要治疗慢性乙肝病毒感染,美国食品药品监督管理局(FDA)列为B类妊娠药物的替诺福韦是首选。核苷(酸)类似物可用于降低乙肝病毒宫内传播和围产期传播的风险,尽管进行了主动和被动免疫,但部分高病毒载量母亲的新生儿仍可能发生这种传播。同样,对于高病毒血症的孕妇,在妊娠晚期推荐使用替诺福韦。在化疗或免疫抑制治疗期间及之后,包括使用生物反应调节剂(特别是与利妥昔单抗治疗相关时),乙肝表面抗原阳性患者及隐匿性乙肝病毒感染患者发生慢性乙肝病毒感染再激活的风险很高。因此,所有接受这些治疗的患者都应筛查乙肝表面抗原和乙肝核心抗体(抗 - HBc)。对于乙肝表面抗原阳性患者及隐匿性乙肝病毒感染患者,应开始进行预防性核苷(酸)类似物治疗。强调了全科医生和职业健康医生在乙肝病毒感染识别和预防方面的作用。本文还回顾了高危人群、疫苗接种适应证以及主动和被动免疫方法等问题。

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