title: Validity of diagnostic codes and laboratory tests of liver dysfunction to identify acute liver failure events.
abstract: OBJECTIVE
  Identification of acute liver failure (ALF) is important for post-marketing surveillance of medications, but the validity of using ICD-9 diagnoses and laboratory data to identify these events within electronic health records is unknown. We examined positive predictive values (PPVs) of hospital ICD-9 diagnoses and laboratory tests of liver dysfunction for identifying ALF within a large, community-based integrated care organization.
  
  
  METHODS
  We identified Kaiser Permanente Northern California health plan members (2004-2010) with a hospital diagnosis suggesting ALF (ICD-9 570, 572.2, 572.4, 572.8, 573.3, 573.8, or V42.7) plus an inpatient international normalized ratio ≥1.5 (off warfarin) and total bilirubin ≥5.0 mg/dL. Hospital records were reviewed by hepatologists to adjudicate ALF events. PPVs for confirmed outcomes were determined for individual ICD-9 diagnoses, diagnoses plus prescriptions for hepatic encephalopathy treatment, and combinations of diagnoses in the setting of coagulopathy and hyperbilirubinemia.
  
  
  RESULTS
  Among 669 members with no pre-existing liver disease, chart review confirmed ALF in 62 (9%). Despite the presence of co-existing coagulopathy and hyperbilirubinemia, individual ICD-9 diagnoses had low PPVs (range, 5-15%); requiring prescriptions for encephalopathy treatment did not increase PPVs of these diagnoses (range, 2-23%). Hospital diagnoses of other liver disorders (ICD-9 573.8) plus hepatic coma (ICD-9 572.2) had high PPV (67%; 95%CI, 9-99%) but only identified two (3%) ALF events.
  
  
  CONCLUSIONS
  Algorithms comprising relevant hospital diagnoses, laboratory evidence of liver dysfunction, and prescriptions for hepatic encephalopathy treatment had low PPVs for confirmed ALF events. Studies of ALF will need to rely on medical records to confirm this outcome.
authors: Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Vincent
authors: V
authors: Lo Re
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Dena M
authors: DM
authors: Carbonari
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Kimberly A
authors: KA
authors: Forde
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: David
authors: D
authors: Goldberg
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: James D
authors: JD
authors: Lewis
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Kevin
authors: K
authors: Haynes
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Kimberly B F
authors: KB
authors: Leidl
authors: Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Rajender K
authors: RK
authors: Reddy
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Jason
authors: J
authors: Roy
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Daohang
authors: D
authors: Sha
authors: Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors: Amy R
authors: AR
authors: Marks
authors: Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors: Jennifer L
authors: JL
authors: Schneider
authors: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Rutgers Biomedical & Health Sciences, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors: Brian L
authors: BL
authors: Strom
authors: Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
authors: Douglas A
authors: DA
authors: Corley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002140:California / Q000453:epidemiology; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000453:epidemiology* / Q000209:etiology; D059019:Clinical Coding; D003430:Cross-Sectional Studies; D006801:Humans; D038801:International Classification of Diseases; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000175:diagnosis* / Q000453:epidemiology*; D008111:Liver Function Tests; D008875:Middle Aged; D017891:Pharmacoepidemiology; D011237:Predictive Value of Tests; D011358:Product Surveillance, Postmarketing
keywords: ICD-9 codes; acute liver failure; hepatotoxicity; liver injury; pharmacoepidemiology; validity