抗病毒与化疗共同治疗肝炎癌症患者

编辑:庄云芳

文献标题：Antivirals and chemotherapy: Managing cancer patients with hepatitis
文献来源：Category: Vienna 2012 App, Vienna 2012 Congress

活动性乙肝病毒（HBV）和丙肝病毒（HCV）在世界范围内非常普遍。全世界大约有三分之一的人口（超过20亿人）感染过乙肝病毒并且慢性乙肝病毒感染者有3.5亿。在1.5亿慢性丙肝病毒感染者，大约每年有35万人死于HCV相关的肝脏疾病。

根据WHO估计，每年大约有一百万人死于HBV和HCV相关的肝脏疾病。

2012年在维也纳召开的欧洲肿瘤学年会上一个名为“支持治疗的关键主题”的特殊研讨会上，来自澳大利亚墨尔本东部卫生组织的John Lubel医生提出了正在接受治疗的HBV和HCV患者的治疗策略和方法。他说：个性化的治疗策略是很有必要的，因为这两种病毒的病毒学、自然史不同，相应的，它们的治疗方法不同。

慢性病毒性肝炎患者宿主的免疫和病毒复制是平衡的，这就导致人体的免疫抑制在病毒复制中发挥不了作用。在非肝硬化的丙肝患者中很少有严重的并发症；丙肝患者接受像化疗这样的免疫抑制治疗大部分都需要检测。

相比较而言，乙肝患者在接受免疫抑制治疗期间会出现复发的情况，这会导致肝功能衰竭；在一些最极端的情况下需要肝移植甚至导致患者死亡。尽管乙肝病毒不能杀死细胞，免疫介导损伤的炎症反应以及在最大免疫抑制期间后发生的炎症反应危害很大。为了防止这种炎症反应，Lubel医生建议慢性乙肝患者在接受免疫抑制治疗前服用抗病毒药物预防并且在接受完免疫治疗后仍要服用抗病毒药物一年。

高病毒载量的患者需要服用像恩替卡韦和替诺福韦这样的抗病毒药物；这些药物对病毒耐药具有很高的药效。对低载量或测不到病毒载量的患者，使用拉米夫定就可以了。

Lubel医生警告说在似乎已经清除乙肝病毒感染的患者中，激活的病毒可以在肝炎复发后的表面抗原中再现。他同时也指出这种情况似乎特别容易出现在包含抗CD20抗体（美罗华）的治疗方案中。因此，不能通过HBV DNA定量和肝功能检查密切监测病毒复制的患者也应接受抗病毒药物预防治疗。

Lubel医生建议对乙肝病毒和丙肝病毒的管理应该在肝脏科医生的范围内。“肿瘤科医生的重要职责是认识到问题并且在适当的时候进行检查。”Lubel医生说。

abstract

Active hepatitis B virus (HBV) and hepatitis C virus (HCV) are highly prevalent around the world. Approximately one third of the world’s population (over 2 billion people) has been infected with HBV and 350 million have chronic HBV infection. Around 150 million people have chronic HCV infection and 350,000 people die annually from HCV-related liver diseases.

According to the World Health Organization (WHO), 1 million people a year die from HBV- and HCV- related liver disease.

In a special symposium at ESMO 2012 Vienna on ‘Key topics in supportive care’, Dr John Lubel of Eastern Health, Melbourne, Australia, presented strategies and approaches to dealing with patients infected by HBV and HCV who are undergoing chemotherapy. Different strategies are necessary for their effective treatment, he said, because the two viruses differ significantly in virology, natural history and therefore management approaches.

In chronic viral hepatitis there is equilibrium between the host’s immunity and viral replication, resulting in immunosuppression that doesn’t inhibit viral replication. In non-cirrhotic HCV patients, this rarely results in significant complications; HCV patients undergoing immunosuppressive therapy, such as chemotherapy, generally just require monitoring.

In contrast, patients with HBV may have significant hepatitis ‘flares’ following periods of immunosuppression which may lead to hepatic failure, the need for liver transplant or death in the most extreme cases. Although HBV does not kill cells, inflammation results from immune-mediated injury and therefore generally occurs following periods of maximal immunosuppression. To prevent such reactivation, Dr Lubel recommended that patients with chronic HBV take antiviral prophylaxis prior to immunosuppressive chemotherapy and remain on antivirals for a year after chemotherapy is finished.

Patients with high viral loads should take antiviral agents such as entecavir and tenofovir; these drugs have a high genetic barrier to viral resistance. Lamivudine is acceptable for patients with low or undetectable viral loads.

Dr Lubel warned that in patients who seem to have cleared their hepatitis B infection, reactivation of the virus can occur with the subsequent reappearance of surface antigen (seroreversion) followed by clinically significant HBV flares. He also noted that the risk of this seems to be particularly high for chemotherapy regimens containing the anti CD20 antibody, Rituximab. Thus, patients who cannot be closely monitored for virus reactivation through monthly HBV DNA quantification and liver function tests should also receive antiviral prophylaxis.

Dr Lubel advised that the management of HBV and HCV should be in the domain of the hepatologist. “The essential role of the the the oncologist is to be aware of the problem and screen appropriately”, said Dr Lubel.