title: Relationship between characteristics of medications and drug-induced liver disease phenotype and outcome.
abstract: OBJECTIVE
  It is not known whether specific characteristics of medication are associated with type of drug-induced liver injury (DILI) or outcome. We examined the relationships among select characteristics of medications and DILI phenotype and outcome.
  
  
  METHODS
  We analyzed 383 cases of DILI caused by a single orally administered prescription agent from the DILI Network Prospective Study with causalities of definite, highly likely, or probable. Relationship of daily dosage (≥50 mg vs ≤49 mg), preponderance of hepatic metabolism (≥50% vs <50%), or Biopharmaceutics Drug Disposition Classification System (BDDCS) class (1-4, based on solubility and metabolism of the drug) were compared with clinical characteristics and outcomes.
  
  
  RESULTS
  Compared with cases of DILI in the ≤49 mg/day group, those associated with daily dosages ≥50 mg had shorter latency (median, 38 days vs 56 days; P = .03) and a different biochemical pattern of liver injury (P = .04); no differences in recovery, severity, or outcome were observed. Patients with DILI caused by medications with or without preponderant hepatic metabolism did not differ in clinical characteristics or outcomes. Compared with other classes of BDDCS, DILI caused by BDDCS class 1 medications had significantly longer latency (P < .001) and greater proportion of hepatocellular injury (P = .001). However, peak liver biochemical values and patients' time to recovery, disease severity, and outcomes did not differ among the 4 BDDCS classes.
  
  
  CONCLUSIONS
  Characteristics of medications (dosage, hepatic metabolism, and solubility) are associated with features of DILI such as latency and pattern of liver injury, but not with recovery, severity, or outcome.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Raj
authors.initials: R
authors.lastname: Vuppalanchi
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Raghavender
authors.initials: R
authors.lastname: Gotur
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Marwan
authors.initials: M
authors.lastname: Ghabril
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Kosinski
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Jiezhun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jose
authors.initials: J
authors.lastname: Serrano
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: nchalasa@iu.edu.
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
mesh_terms: D000328:Adult; D000368:Aged; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000401:mortality / Q000473:pathology*; D004358:Drug Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
keywords: ALT; DILIN; Liver Toxicity; Overdose; Side Effect