title: Case series of liver failure associated with rosiglitazone and pioglitazone.
abstract: OBJECTIVE
  The thiazolidinedione drugs rosiglitazone and pioglitazone are not widely known to be hepatotoxic. We evaluated the FDA Adverse Event Reporting System (AERS) to determine the number of reported cases of liver failure associated with rosiglitazone and pioglitazone between 1997 and 2006, and described their clinical characteristics.
  
  
  METHODS
  Adverse event reports spontaneously submitted to the FDA AERS from 1997 to 2006 were examined. Liver failure associated with rosiglitazone or pioglitazone was defined as liver injury accompanied by hepatic encephalopathy, liver transplantation, placement on a liver transplant list, or death in which all other likely etiologies were excluded. Using prescribing data, the number of reported cases of liver failure per million patient-years of exposure was calculated for each drug.
  
  
  RESULTS
  Twenty-one cases met our case definition. Clinical characteristics, outcomes, and pathologic data were similar between cases of liver failure associated with rosiglitazone and with pioglitazone. The median duration of therapy was 9 weeks and 85% of cases were acute, defined as symptom onset to liver failure in less than 26 weeks. The case-fatality rate was 81% (17/21), and only 14% (3/21) spontaneously recovered. Accounting for underreporting, the number needed to harm (NNH) for each case of liver failure was 44 000 patient-years of exposure for rosiglitazone and 52 000 patient-years of exposure for pioglitazone.
  
  
  CONCLUSIONS
  This is the largest case series of liver failure associated with rosiglitazone or pioglitazone reported to date, strengthening the evidence that these drugs can cause severe hepatotoxicity.
authors.affiliation: Public Citizen, Health Research Group, 1600 20th Street NW, Washington, DC 20009, USA. jfloyd@citizen.org
authors.forename: James S
authors.initials: JS
authors.lastname: Floyd
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barbehenn
authors.forename: Peter
authors.initials: P
authors.lastname: Lurie
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Wolfe
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017093:Liver Failure / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone