Simpson Nicole D, Simpson Peter W, Ahmed Ali M, Nguyen Mindie H, Garcia Gabriel, Keeffe Emmet B, Ahmed Aijaz
Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94304, USA.
J Clin Gastroenterol. 2003 Jul;37(1):68-71. doi: 10.1097/00004836-200307000-00017.
The results of lamivudine therapy in 4 patients with chemotherapy-induced hepatitis B virus (HBV) reactivation are reported. Cancer chemotherapy-induced reactivation is a known complication in patients with chronic HBV infection or history of HBV infection with recovery. Reactivation of HBV infection has a broad spectrum of manifestations ranging from mild elevation of aminotransferase levels to fatal fulminant hepatitis. Lamivudine is a nucleoside analogue and a potent inhibitor of HBV reverse transcription. The 4 patients treated with lamivudine included 1 woman with breast cancer and 3 men with non-Hodgkin lymphoma, ranging from 41 to 63 years of age. All 4 patients were undergoing standard, multi-agent chemotherapy when they presented with HBV reactivation manifested by sudden onset of fatigue, jaundice, and HBV serology consistent with active HBV infection (detectable serum HBV DNA) in the absence of other known causes of acute hepatitis. Lamivudine therapy (100 mg/d in 3 patients and 150 mg/d in 1 patient) was initiated from 1 to 18 days following the diagnosis of HBV reactivation. All 4 patients showed rapid decrease in aminotransferase levels within 2 weeks after initiating lamivudine therapy. Unfortunately, hepatic synthetic function failed to improve in 2 patients, who both died. The remaining 2 patients had suppression of HBV DNA to undetectable levels after 1 and 4 months of treatment and had biochemical and clinical improvement. The 2 patients who died received lamivudine therapy for 8 days and for 3 weeks. There have been no randomized clinical trials to study the role of lamivudine for prophylaxis or treatment of HBV reactivation associated with chemotherapy. However, based on our limited experience, lamivudine may be efficacious in suppressing potentially fatal HBV reactivation secondary to chemotherapy in patients with chronic HBV infection or prior infection with recovery. Patients who undergo chemotherapy should be screened for the presence of markers of chronic hepatitis B infection or previous HBV infection. We recommend that patients with chronic HBV infection (positive HBV DNA and/or positive HBsAg) or history of HBV infection with recovery (positive hepatitis B core antibody with or without HBsAb) be considered for prophylactic lamivudine use to prevent chemotherapy-induced HBV reactivation.
报告了4例化疗诱导的乙型肝炎病毒(HBV)再激活患者接受拉米夫定治疗的结果。癌症化疗诱导的再激活是慢性HBV感染患者或有HBV感染恢复史患者的一种已知并发症。HBV感染再激活有广泛的表现,从转氨酶水平轻度升高到致命的暴发性肝炎。拉米夫定是一种核苷类似物,是HBV逆转录的有效抑制剂。接受拉米夫定治疗的4例患者包括1例乳腺癌女性和3例非霍奇金淋巴瘤男性,年龄在41至63岁之间。所有4例患者在出现HBV再激活时均正在接受标准的多药化疗,表现为突然出现疲劳、黄疸,且HBV血清学检查结果与活动性HBV感染一致(可检测到血清HBV DNA),且无其他已知的急性肝炎病因。在诊断HBV再激活后的1至18天开始拉米夫定治疗(3例患者每日100 mg,1例患者每日150 mg)。所有4例患者在开始拉米夫定治疗后2周内转氨酶水平迅速下降。不幸的是,2例患者的肝脏合成功能未能改善,两人均死亡。其余2例患者在治疗1个月和4个月后HBV DNA被抑制到无法检测的水平,生化指标和临床症状均有改善。死亡的2例患者接受拉米夫定治疗的时间分别为8天和3周。目前尚无随机临床试验研究拉米夫定在预防或治疗与化疗相关的HBV再激活中的作用。然而,根据我们有限的经验,拉米夫定可能有效地抑制慢性HBV感染或既往感染恢复患者化疗继发的潜在致命性HBV再激活。接受化疗的患者应筛查慢性乙型肝炎感染标志物或既往HBV感染情况。我们建议,对于慢性HBV感染(HBV DNA阳性和/或HBsAg阳性)或有HBV感染恢复史(乙肝核心抗体阳性,有或无HBsAb)的患者,应考虑预防性使用拉米夫定以预防化疗诱导的HBV再激活。