title: Antithyroid drug-related   hepatotoxicity in    hyperthyroidism patients:   a population-based   cohort study.
abstract: OBJECTIVE
  The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population-based manner.
  
  
  METHODS
  We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non-infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively.
  
  
  RESULTS
  The study cohort comprised 71 379 ATD initiators, with a median follow-up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person-years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person-years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89-fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08-fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22).
  
  
  CONCLUSIONS
  MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose-dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.
authors.forename: Meng-Ting
authors.initials: MT
authors.lastname: Wang
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Lee
authors.forename: Tien-Yu
authors.initials: TY
authors.lastname: Huang
authors.forename: Che-Li
authors.initials: CL
authors.lastname: Chu
authors.forename: Chang-Hsun
authors.initials: CH
authors.lastname: Hsieh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D013956:Antithyroid Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002231:Carbimazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D015331:Cohort Studies; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy*; D015994:Incidence; D008297:Male; D008713:Methimazole / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D016016:Proportional Hazards Models; D011441:Propylthiouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013624:Taiwan; D055815:Young Adult
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D011441:Propylthiouracil; D002231:Carbimazole