Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
Hepatology. 2014 Jun;59(6):2092-100. doi: 10.1002/hep.26718. Epub 2014 Apr 14.
Fatal hepatitis B virus (HBV) reactivation in lymphoma patients with "resolved" HBV infection (hepatitis B surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) can occur, but the true incidence and severity remain unclear. From June 2009 to December 2011, 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy were prospectively followed. HBV DNA was checked at baseline, at the start of each cycle of chemotherapy, and every 4 weeks for 1 year after completion of rituximab-CHOP chemotherapy. Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks. HBV reactivation was defined as a greater than 10-fold increase in HBV DNA, compared with previous nadir levels, and hepatitis flare was defined as a greater than 3-fold increase in alanine aminotransferase (ALT) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV-related hepatitis flares was 10.4 and 6.4 per 100 person-year, respectively. Severe HBV-related hepatitis (ALT >10-fold of upper limit of normal) occurred in 4 patients, despite entecavir treatment. Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation (100% vs. 28.5%; P=0.003).
In lymphoma patients with resolved HBV infections, chemotherapy-induced HBV reactivation is not uncommon, but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy. Serological breakthrough (i.e., reappearance of HBsAg) is the most important predictor of HBV-related hepatitis flare. (Hepatology 2014;59:2092-2100).
研究在接受利妥昔单抗 - CHOP（环磷酰胺、阿霉素、长春新碱、泼尼松）为基础的化疗的“已解决”乙型肝炎病毒（HBV）感染（乙型肝炎表面抗原 [HBsAg] 阴性和乙型肝炎核心抗体 [抗-HBc] 阳性）的淋巴瘤患者中，HBV 再激活导致的致命性肝炎的真实发生率和严重程度。
2009 年 6 月至 2011 年 12 月，前瞻性随访了 150 例新诊断为淋巴瘤且 HBV 感染已解决的患者，他们将接受利妥昔单抗 - CHOP 为基础的化疗。在基线时、每个化疗周期开始时以及完成利妥昔单抗 - CHOP 化疗后的 1 年内每 4 周检查一次 HBV DNA。记录到 HBV 再激活的患者接受恩替卡韦（0.5mg/天）治疗 48 周。HBV 再激活定义为 HBV DNA 较之前的最低水平增加 10 倍以上，肝炎爆发定义为丙氨酸氨基转移酶（ALT）增加 3 倍以上，超过 100IU/L。HBV 再激活和 HBV 相关肝炎爆发的发生率分别为 10.4 和 6.4/100 人年。尽管进行了恩替卡韦治疗，但仍有 4 例患者发生严重的 HBV 相关肝炎（ALT 高于正常值上限的 10 倍）。发生肝炎爆发的患者 HBV 再激活后 HBsAg 再次出现的发生率明显更高（100%比 28.5%；P=0.003）。
在淋巴瘤患者中，接受利妥昔单抗 - CHOP 化疗的患者中 HBV 再激活并不罕见，但通过定期监测 HBV DNA 并及时进行抗病毒治疗可以得到很好的控制。血清学突破（即 HBsAg 再次出现）是 HBV 相关肝炎爆发的最重要预测因素。
