title: Probable drug-induced liver injury associated with aliskiren: case report and review of adverse event reports from pharmacovigilance databases.
abstract: OBJECTIVE
  A case of probable drug-induced liver injury (DILI) attributed to use of the antihypertensive agent aliskiren is reported.
  
  
  CONCLUSIONS
  A 61-year-old woman undergoing routine liver function monitoring in conjunction with long-term antiepileptic therapy was noted to have an asymptomatic acute hepatic cytolysis 1 month after the initiation of concomitant aliskiren therapy (150 mg/day). Liver enzyme testing showed dramatically elevated aspartate transaminase (AST) and alanine transaminase (ALT) concentrations, with substantial rises also noted in γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) levels. The calculated ALT:ALP value indicated hepatocellular injury. On discontinuation of aliskiren use, rapid biological improvement occurred, including normalization of serum AST and a sharp decline in serum ALT within one week and the return of GGT and ALP levels to baseline a few weeks later; the patient's AST and ALT concentrations remained normal during 18 months of subsequent monitoring. Using the algorithm of Naranjo et al. and a DILI-specific causality assessment instrument, it was determined that aliskiren use was the probable cause of the patient's liver injury. While this is believed to be the first report of aliskiren-associated DILI in the professional literature, a review of information from several European and North American pharmacovigilance databases (through October 2012) identified 117 reports of suspected aliskiren hepatotoxicity, including 6 reports of liver failure and 12 reports of deaths.
  
  
  CONCLUSIONS
  Asymptomatic acute hepatic cytolysis was observed in a 61-year-old woman approximately one month after initiation of aliskerin for treatment of hypertension. Improvement in AST and ALT concentrations was observed shortly after the drug was discontinued.
authors.affiliation: Sabrina Crepin, Pharm.D., M.P.H., is Hospital Pharmacist, Department of Pharmacology-Toxicology, Pharmacovigilance; Bertrand Godet, M.D., is Neurologist, Department of Neurology; and Paul Carrier, M.D., is Hepatologist, Department of Hepatogastroenterology, Limoges University Hospital, Limoges, France. Claire Villeneuve, M.S.I., is Clinical Research Associate; Louis Merle, Ph.D., M.D., is Pharmacologist; and Marie-Laure Laroche, Ph.D., M.D., is Pharmacologist, Department of Pharmacology-Toxicology, Pharmacovigilance, Limoges University Hospital.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Crepin
authors.forename: Bertrand
authors.initials: B
authors.lastname: Godet
authors.forename: Paul
authors.initials: P
authors.lastname: Carrier
authors.forename: Claire
authors.initials: C
authors.lastname: Villeneuve
authors.forename: Louis
authors.initials: L
authors.lastname: Merle
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Laroche
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000577:Amides / Q000009:adverse effects*; D000959:Antihypertensive Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000503:physiopathology; D016208:Databases, Factual; D005260:Female; D005650:Fumarates / Q000009:adverse effects*; D006801:Humans; D008111:Liver Function Tests; D008875:Middle Aged; D060735:Pharmacovigilance
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; C446481:aliskiren; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase