Locasciulli A, Mura R, Fraschini D, Gornati G, Scovena E, Gervasoni A, Uderzo C, Masera G
Clinica Pediatrica, Università di Milano, Ospedale S. Gerardo, Monza, Italy.
Haematologica. 1992 Jan-Feb;77(1):49-53.
Methotrexate-induced hepatotoxicity following chronic low-dose administration has been extensively reported. Current protocols now include high-dose methotrexate (HDMTX), but there are few studies providing data on its acute hepatotoxicity in childhood leukemia.
To evaluate the prevalence of HDMTX-induced acute hepatotoxicity, sixty-eight consecutive children with ALL were prospectively studied from diagnosis to the end of HDMTX courses with biochemical and clinical evaluation performed at regular intervals.
Prevalence of HDMTX-induced acute hepatotoxicity was 1.47% (1/68 patients). ALT values did not change in 22% (15/68) and decreased in 76.4% (52/68) after HDMTX infusion. Mean ALT levels calculated in all the patients decreased significantly during HDMTX administration when compared to the values reached during induction (p less than 0.0001). Direct hyperbilirubinemia was present only in the child with HDMTX-related hepatotoxicity.
The use of HDMTX in the treatment of childhood ALL is not associated with major evidence of direct acute hepatotoxic effects, while it may modify the pattern of preexisting liver diseases.
长期低剂量给药后甲氨蝶呤诱导的肝毒性已有大量报道。目前的方案现在包括高剂量甲氨蝶呤（HDMTX），但很少有研究提供其在儿童白血病中急性肝毒性的数据。
为评估HDMTX诱导的急性肝毒性的发生率，对68例连续的急性淋巴细胞白血病患儿从诊断到HDMTX疗程结束进行前瞻性研究，定期进行生化和临床评估。
HDMTX诱导的急性肝毒性发生率为1.47%（1/68例患者）。HDMTX输注后，22%（15/68）的患者谷丙转氨酶（ALT）值未改变，76.4%（52/68）的患者ALT值下降。与诱导期达到的值相比，HDMTX给药期间所有患者计算的平均ALT水平显著降低（p<0.0001）。直接胆红素血症仅出现在与HDMTX相关肝毒性的患儿中。
HDMTX用于治疗儿童急性淋巴细胞白血病与直接急性肝毒性的主要证据无关，但其可能改变既往存在的肝脏疾病模式。
