title: Acute liver injury induced by levetiracetam and temozolomide co-treatment.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We sought to determine the risk of liver injury associated with the co-administration of TMZ and LEV.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Combination therapy with TMZ and LEV may precipitate acute liver injury and even death.
authors.affiliation: Department of Internal Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Gastroenterology and Liver Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: tawfikkhoury1@hotmail.com.
authors.forename: Tawfik
authors.initials: T
authors.lastname: Khoury
authors.affiliation: Cardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: shmuel.chen@mail.huji.ac.il.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: Aymansar@gmail.com.
authors.forename: Ayman
authors.initials: A
authors.lastname: Abu Rmeileh
authors.affiliation: Department of Internal Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Gastroenterology and Liver Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: saleh@hadassah.org.il.
authors.forename: Saleh
authors.initials: S
authors.lastname: Daher
authors.affiliation: Department of Internal Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Department of Gastroenterology and Liver Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: yaari@hadassah.org.il.
authors.forename: Shaul
authors.initials: S
authors.lastname: Yaari
authors.affiliation: Department of Gastroenterology and Liver Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel. Electronic address: ari.benson@gmail.com.
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Benson
authors.affiliation: Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: jmcohen@bidmc.harvard.edu.
authors.forename: Jonah
authors.initials: J
authors.lastname: Cohen
authors.affiliation: Center for Advanced Endoscopy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: mmizrahi@bidmc.harvard.edu.
authors.forename: Meir
authors.initials: M
authors.lastname: Mizrahi
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000401:mortality; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007557:Israel; D000077287:Levetiracetam; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives*; D012044:Regression Analysis; D012189:Retrospective Studies; D000077204:Temozolomide
chemical_list: D000927:Anticonvulsants; D018906:Antineoplastic Agents, Alkylating; D000077287:Levetiracetam; D003606:Dacarbazine; D000077204:Temozolomide; D010889:Piracetam
keywords: Drug induced liver injury; Levetiracetam; Temozolomide