Department of Digestive and Lifestyle-related Diseases, Health Research Course, Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Hepatol Res. 2012 Jul;42(7):627-36. doi: 10.1111/j.1872-034X.2012.00998.x.
With the increasing use of potent immunosuppressive therapy, reactivation of hepatitis B virus (HBV) in endemic regions is becoming a clinical problem requiring special attention. A recent annual nationwide survey clarified that HBV reactivation related to immunosuppressive therapy has been increasing in patients with malignant lymphoma, other hematological malignancies, oncological or rheumatological disease. In the survey, rituximab plus steroid-containing chemotherapy was identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg) negative patients with malignant lymphoma. In this setting, HBV reactivation resulted in fatal fulminant hepatitis regardless of the treatment of nucleoside analog. The Intractable Hepatobiliary Disease Study Group and the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis jointly developed guidelines for preventing HBV reactivation. The essential features of the guideline are as follows. All patients should be screened for HBsAg by a sensitive method before the start of immunosuppressive therapy. Second, hepatitis B core antigen (HBcAb) and hepatitis B surface antibody (HBsAb) testing should be performed in HBsAg negative patients, especially those receiving intensive immunosuppressive therapy. Prophylaxis with nucleoside analogs is essential for preventing HBV reactivation in HBsAg positive patients. In contrast, HBsAg negative with HBcAb and/or HBsAb positive patients should be monitored monthly for an increase in serum HBV DNA during and 12 months after completion of chemotherapy. Nucleoside analogs should be administrated immediately when HBV DNA becomes positive during this period. This strategy facilitates commencement of nucleoside analogs at an early stage of HBV reactivation and results in prevention of severe hepatitis.
随着强效免疫抑制剂治疗的广泛应用，乙型肝炎病毒（HBV）在流行地区的再激活正成为一个需要特别关注的临床问题。最近一项全国年度调查阐明，恶性淋巴瘤、其他血液系统恶性肿瘤、肿瘤或风湿性疾病患者的免疫抑制治疗相关 HBV 再激活病例不断增加。在该调查中，利妥昔单抗联合含激素化疗被确定为乙型肝炎表面抗原（HBsAg）阴性恶性淋巴瘤患者 HBV 再激活的危险因素。在此背景下，无论是否使用核苷类似物治疗，HBV 再激活均可导致致命性暴发性肝炎。日本难治性肝胆病学会和病毒性肝炎包括肝硬化治疗标准化研究组共同制定了预防 HBV 再激活的指南。该指南的主要特点如下。所有患者在开始免疫抑制治疗前应通过敏感方法筛查 HBsAg。其次，HBsAg 阴性患者，尤其是接受强化免疫抑制治疗的患者，应进行乙型肝炎核心抗原（HBcAg）和乙型肝炎表面抗体（HBsAb）检测。HBsAg 阳性患者预防 HBV 再激活需要核苷类似物预防。相反，HBsAg 阴性、HBcAb 和/或 HBsAb 阳性的患者应在化疗期间及结束后 12 个月内每月监测血清 HBV DNA 水平，以观察是否增加。在此期间，如果 HBV DNA 阳性，应立即给予核苷类似物。该策略有利于在 HBV 再激活的早期阶段开始核苷类似物治疗，从而预防严重肝炎。
