title: Incidence of liver injury among cancer patients receiving chemotherapy in an integrated health system.
abstract: OBJECTIVE
  Using liver laboratory tests (LLTs), Hy's law is a method used to identify drug-induced liver injury (DILI), after excluding other causes. Elevated LLTs in chemotherapy-exposed patients may result from tumor effects or comorbidities. This study evaluated incidence of Hy's law in chemotherapy-treated cancer patients.
  
  
  METHODS
  We identified breast, colorectal, and lung cancer patients diagnosed in 1 January 2000 to 31 December 2007 at a Midwestern health system. Using automated data, potential Hy's law (PHL) cases were defined by patterns of elevated LLTs suggestive of DILI. Among those treated with chemotherapy, we excluded PHL patients with pre-existing conditions that could cause liver injury, producing a cohort meeting Hy's law criteria, according to automated data. Medical record review, conducted among these automated data-derived Hy's law patients, further excluded those with causes of liver injury other than chemotherapy.
  
  
  RESULTS
  Using automated data, among chemotherapy-exposed patients (N = 2788), 91 (3.3%) met PHL criteria using LLTs and 64 (2.3%) met Hy's law after excluding underlying liver injury using the International Classification of Diseases, 9th Revision codes. After a medical record review, 62 of 64 patients qualifying as Hy's law through automated data had other potential causes, leaving two patients (0.07%; 95%CI: 0.01-0.24%) with chemotherapy as a likely alternative cause of liver injury.
  
  
  CONCLUSIONS
  Abnormal LLTs are common in chemotherapy-treated patients. Medical record review showed that the incidence of Hy's law events is rare. These data provide context for evaluating DILI in clinical trials and postmarketing surveillance of anticancer therapies, understanding that automated data alone may substantially overestimate the number of Hy's law cases.
authors: EpiSource LLC, Newton, MA, USA; Boston University School of Public Health, Boston, MA, USA.
authors: Marianne
authors: M
authors: Ulcickas Yood
authors: Michele
authors: M
authors: Bortolini
authors: Deborah
authors: D
authors: Casso
authors: Jean G
authors: JG
authors: Beck
authors: Susan A
authors: SA
authors: Oliveria
authors: Karen E
authors: KE
authors: Wells
authors: Kimberley J
authors: KJ
authors: Woodcroft
authors: Lisa I
authors: LI
authors: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015146:Midwestern United States / Q000453:epidemiology; D009369:Neoplasms / Q000145:classification / Q000188:drug therapy*; D012042:Registries; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents
keywords: DILI; Hy's law; cancer; chemotherapy; drug-induced liver injury; liver injury; pharmacoepidemiology