Hui Chee-Kin, Cheung Winnie W W, Zhang Hai-Ying, Au Wing-Yan, Yueng Yui-Hung, Leung Anskar Y H, Leung Nancy, Luk John M, Lie Albert K W, Kwong Yok-Lam, Liang Raymond, Lau George K K
Centre For The Study of Liver Diseases, The University of Hong Kong, Hong Kong SAR, China.
Gastroenterology. 2006 Jul;131(1):59-68. doi: 10.1053/j.gastro.2006.04.015.
BACKGROUND & AIMS: De novo hepatitis B virus (HBV)-related hepatitis after chemotherapy results in high morbidity and mortality. We evaluate the clinical course of de novo HBV-related hepatitis after chemotherapy.
Two hundred forty-four consecutive hepatitis B surface antigen (HBsAg)-negative lymphoma patients treated with chemotherapy were followed up for a median of 12.4 (range, 0.1-65.0) months. Serially collected serum samples were analyzed for hepatitis, serum HBV DNA, and HBsAg seroreversion.
Eight of the 244 patients (3.3%) developed de novo HBV-related hepatitis. A 100-fold increase in serum HBV DNA preceded de novo HBV-related hepatitis by a median of 18.5 (range, 12-28) weeks. All 8 patients had normal serum alanine aminotransaminase level when the 100-fold increase in serum HBV DNA occurred. Patients with de novo HBV-related hepatitis were more likely to have occult HBV infection before chemotherapy. Direct sequencing results showed that these 8 patients had de novo HBV-related hepatitis from reactivation of occult HBV infection. Three of the 8 patients with de novo HBV-related hepatitis compared with 6 of the 236 patients without de novo HBV-related hepatitis developed fulminant hepatic failure (37.5% vs 2.5%, respectively, P < .001). On multivariate Cox analysis, de novo HBV-related hepatitis was independently associated with a higher risk of fulminant hepatic failure (relative risk, 29.854; 95% confidence interval: 4.844-183.980; P < .001).
Close surveillance for a 100-fold increase in HBV DNA is recommended for HBsAg-negative patients treated with chemotherapy so that early commencement of antiviral therapy can be initiated before the occurrence of de novo HBV-related hepatitis.
化疗后新发乙型肝炎病毒(HBV)相关肝炎会导致高发病率和死亡率。我们评估了化疗后新发HBV相关肝炎的临床病程。
对244例接受化疗的连续乙型肝炎表面抗原(HBsAg)阴性淋巴瘤患者进行了中位时间为12.4(范围0.1 - 65.0)个月的随访。对连续采集的血清样本进行肝炎、血清HBV DNA及HBsAg血清学转换分析。
244例患者中有8例(3.3%)发生了新发HBV相关肝炎。血清HBV DNA升高100倍比新发HBV相关肝炎提前出现,中位时间为18.5(范围12 - 28)周。在血清HBV DNA升高100倍时,所有8例患者的血清丙氨酸氨基转移酶水平均正常。新发HBV相关肝炎患者化疗前更可能存在隐匿性HBV感染。直接测序结果显示,这8例患者新发HBV相关肝炎是由隐匿性HBV感染重新激活所致。8例新发HBV相关肝炎患者中有3例发生了暴发性肝衰竭,而236例未发生新发HBV相关肝炎的患者中有6例发生了暴发性肝衰竭(分别为37.5%和2.5%,P <.001)。多因素Cox分析显示,新发HBV相关肝炎与暴发性肝衰竭风险较高独立相关(相对风险为29.854;95%置信区间:4.844 - 183.980;P <.001)。
对于接受化疗的HBsAg阴性患者,建议密切监测HBV DNA升高100倍的情况,以便在新发HBV相关肝炎发生之前尽早开始抗病毒治疗。