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Pharmacoepidemiol Drug Saf. 2019 Jul;28(7):965-975. doi: 10.1002/pds.4803. Epub 2019 Jun 6.

Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: A study in three European data sources.

Author information

Epidemiology, RTI Health Solutions, Barcelona, Spain.
Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
Institut Català de la Salut, Barcelona, Spain.
EpiChron Research Group. Aragon Health Sciences Institute (IACS), IIS Aragón, REDISSEC ISCIII, Zaragoza, Spain.
Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, Barcelona, Spain.
Pharmacoepidemiology Department, Les Laboratoires Servier, Paris, France.
The Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA.



Validating cases of acute liver injury (ALI) in health care data sources is challenging. Previous validation studies reported low positive predictive values (PPVs).


Case validation was undertaken in a study conducted from 2009 to 2014 assessing the risk of ALI in antidepressants users in databases in Spain (EpiChron and SIDIAP) and the Danish National Health Registers. Three ALI definitions were evaluated: primary (specific hospital discharge codes), secondary (specific and nonspecific hospital discharge codes), and tertiary (specific and nonspecific hospital and outpatient codes). The validation included review of patient profiles (EpiChron and SIDIAP) and of clinical data from medical records (EpiChron and Denmark). ALI cases were confirmed when liver enzyme values met a definition by an international working group.


Overall PPVs (95% CIs) for the study ALI definitions were, for the primary ALI definition, 84% (60%-97%) (EpiChron), 60% (26%-88%) (SIDIAP), and 74% (60%-85%) (Denmark); for the secondary ALI definition, 65% (45%-81%) (EpiChron), 40% (19%-64%) (SIDIAP), and 70% (64%-77%) (Denmark); and for the tertiary ALI definition, 25% (18%-34%) (EpiChron), 8% (7%-9%) (SIDIAP), and 47% (42%-52%) (Denmark). The overall PPVs were higher for specific than for nonspecific codes and for hospital discharge than for outpatient codes. The nonspecific code "unspecified jaundice" had high PPVs in Denmark.


PPVs obtained apply to patients using antidepressants without preexisting liver disease or ALI risk factors. To maximize validity, studies on ALI should prioritize hospital specific discharge codes and should include hospital codes for unspecified jaundice. Case validation is required when ALI outpatient cases are considered.


acute liver injury; antidepressants; pharmacoepidemiology; validation

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