Khoury Tawfik, Chen Shmuel, Abu Rmeileh Ayman, Daher Saleh, Yaari Shaul, Benson Ariel A, Cohen Jonah, Mizrahi Meir
Department of Internal Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Gastroenterology and Liver Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Cardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Dig Liver Dis. 2017 Mar;49(3):297-300. doi: 10.1016/j.dld.2016.11.015. Epub 2016 Dec 5.
Temozolomide (TMZ) is an alkylating agent used for treatment of brain neoplasms and levetiracetam (LEV) is a commonly used antiepileptic. When administered separately each medication has few negative side effects impacting the liver.
We sought to determine the risk of liver injury associated with the co-administration of TMZ and LEV.
A case-control study was performed comparing patients who received combination therapy of TMZ and LEV (group A) with matched controls (group B) who received monotherapy with one of either TMZ or LEV. We assessed patient demographics, laboratory results including presence of liver injury, and mortality.
Twenty-six patients were included in group A and 68 patients were included in group B. Both groups were similar with respect to demographics and baseline liver function tests (P>0.05). There was a significant elevation in liver enzymes in 73%, 46%, 19%, 31% and 27% of ALT, AST, ALK-P, GGT and bilirubin, respectively, in group A, as compared to elevations of 10.3%, 19%, 1.5%, 7% and 1.5%, respectively in group B (P<0.05). One patient in group A died as a result of acute liver failure while no deaths from acute liver failure occurred in group B (P=0.05). Univariate analysis identified combination therapy as a risk factor for liver injury. Multivariate regression showed that only co-treatment with TMZ and LEV was an independent risk factor for liver injury with an odds ratio of 19.1 (95 CI, 2.16-160).
Combination therapy with TMZ and LEV may precipitate acute liver injury and even death.
替莫唑胺（TMZ）是一种用于治疗脑肿瘤的烷化剂，左乙拉西坦（LEV）是一种常用的抗癫痫药物。单独使用时，每种药物对肝脏的不良副作用都很少。
我们试图确定TMZ和LEV联合使用与肝损伤风险之间的关系。
进行了一项病例对照研究，将接受TMZ和LEV联合治疗的患者（A组）与接受TMZ或LEV单一疗法的匹配对照组（B组）进行比较。我们评估了患者的人口统计学特征、实验室检查结果（包括肝损伤情况）和死亡率。
A组纳入26例患者，B组纳入68例患者。两组在人口统计学特征和基线肝功能检查方面相似（P>0.05）。A组中谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（ALK-P）、γ-谷氨酰转肽酶（GGT）和胆红素升高的比例分别为73%、46%、19%、31%和27%，而B组分别为10.3%、19%、1.5%、7%和1.5%（P<0.05）。A组有1例患者因急性肝衰竭死亡，而B组无急性肝衰竭死亡病例（P=0.05）。单因素分析确定联合治疗是肝损伤的一个危险因素。多因素回归显示，只有TMZ和LEV联合治疗是肝损伤的独立危险因素，比值比为19.1（95%置信区间，2.16 - 160）。
TMZ和LEV联合治疗可能会引发急性肝损伤甚至死亡。
