Reactivation of precore mutant hepatitis B virus in chemotherapy-treated patients
Reactivation of precore mutant hepatitis B virus in chemotherapy-treated patients
复制标题
DOI：
10.1002/1097-0142(20011201)92:11
复制
发表时间：
2001-12-01
期刊：
影响因子：
6.2
通讯作者：
Chao, TY
中科院分区：
文献类型：
--
作者：
Dai, MS;Lu, JJ;Chao, TY
背景B型肝炎病毒（HBV）DNA前C区1896位核苷酸（nt）由G突变为A，与重型肝炎和重型肝炎有关。进一步的研究表明，这种点突变，加上额外的前C启动子突变，可能与接受细胞毒性化疗的患者中HBV的再激活有关。台湾是一个高流行率的地区，其中B型肝炎的爆发已成为一个严重的问题，乙肝病毒携带者谁必须依靠化疗来治疗他们的疾病。本研究的目的是检查在台湾的中国人化疗后发生严重肝病的患者中是否也存在nt 1896突变。1994年2月至2000年5月，13名乙型肝炎病毒携带者患者，包括8名淋巴瘤患者、2名生殖细胞肿瘤患者、2名乳腺癌患者和1名急性髓性白血病患者，在作者所在医院接受了化疗。他们在化疗期间都接受了含类固醇的方案或止吐药。这些患者在化疗期间或化疗后密切监测重型肝炎的发展。分别于不同时间收集血清，进行HBV DNA前C区聚合酶链反应产物直接测序。13例患者中有6例在化疗期间或化疗完成后发生了重型肝炎。在这6例患者中的5例中检测到nt 1896处从G到A的点突变。在这五名患者中，有四名患者有额外的前核心突变。另一名患者没有nt 1896突变，但有nt 1835突变（A至C）。其他7名缺乏前核心nt 1896突变的患者没有发生重型肝炎。7例出现丙氨酸氨基转移酶（ALT）中度升高但无高胆红素血症的患者中有1例确实存在nt 1896以外的前C区突变。其他6例患者均未发生前核心区突变。前C区的核苷酸突变，特别是在位置1896，与化疗期间或化疗后HBV的暴发性再活化有关。目前的数据以及其他研究者的发现表明，对于HBV包膜抗原（HBeAg）（-）/抗HBV包膜抗体（Anti-HBe）（+）状态的HBV携带者，应在化疗前进行检测，以确定他们是否携带突变型HBV。对于前C区携带突变型HBV的患者，特别是1896位核苷酸（G → A）的患者，强烈建议在化疗前和化疗期间预防性使用拉米夫定。癌症2001;92：2927-2932. (C)2001年美国癌症
Background. A point mutation from G to A at nucleotide (nt) 1896 of the precore region of hepatitis B virus (HBV) DNA has been shown to be associated with fulminant and severe hepatitis. Further studies have suggested that this point mutation, together with additional mutations in the precore promoter, is probably linked to the reactivation of HBV in patients undergoing cytotoxic chemotherapy. Taiwan is an area with a high prevalence of HBV where hepatitis B flare-up has become a serious problem of HBV carriers who must rely on chemotherapy to treat their diseases. The purpose of this study was to examine if nt 1896 mutation was also present in Chinese patients in Taiwan who developed severe liver disease after chemotherapy.Materials and methods. Thirteen HBV carrier patients, including eight patients with lymphoma, two with germ cell tumors, two with breast carcinomas, and one with acute myeloid leukemia, received chemotherapy in the authors' hospital from February 1994 to May 2000. They all received steroid-containing regimens or antiemetics during chemotherapy. These patients were monitored closely for the development of severe hepatitis during or after chemotherapy. Their sera were harvested at different times for direct sequencing of the polymerase chain reaction products of the precore region of HBV DNA.Results. Six of the 13 patients developed severe hepatitis with a fulminant course during or after the completion of chemotherapy. A point mutation from G to A at nt 1896 was detected in five of these six patients. Among those five patients, four had additional precore mutations. The other patient did not have the nt 1896 mutation but had mutations at nt 1835 (A to C). None of the other seven patients lacking the precore nt 1896 mutation developed severe hepatitis flare-up. One of those seven patients who developed moderate elevation of alanine aminotransferase (ALT) without hyperbilirubinemia did have precore mutations other than nt 1896. None of the other six patients had mutations over the precore region.Conclusions. Nucleotide mutation of the precore region, notably at position 1896, is associated with reactivation of HBV with a fulminant course during or after chemotherapy. The current data, together with other investigators' findings, suggest that patients who are HBV carriers with HBV envelope antigen (HBeAg) (-)/anti-HBV envelope antibody (Anti-HBe)(+) status should be assayed to determine if they carry mutant HBV before chemotherapy. Prophylactic use of lamivudine is strongly recommended for patients who carry mutant HBV at precore region, especially at nt 1896 (G to A), before and during chemotherapy. Cancer 2001;92:2927-2932. (C) 2001 American Cancer.