European Journal of Clinical Pharmacology

, Volume 70, Issue 10, pp 1227–1235 | Cite as

Ascertainment of acute liver injury in two European primary care databases

  • A. RuigómezEmail author
  • R. Brauer
  • L. A. García Rodríguez
  • C. Huerta
  • G. Requena
  • M. Gil
  • Francisco de Abajo
  • G. Downey
  • A. Bate
  • M. Feudjo Tepie
  • M. de Groot
  • R. Schlienger
  • R. Reynolds
  • O. Klungel
Pharmacoepidemiology and Prescription



The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI.


The Clinical Practice Research Datalink (CPRD) in UK and the Spanish “Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria” (BIFAP) were used. Both are primary care databases from which we selected individuals of all ages registered between January 2004 and December 2009. We developed two case definitions of idiopathic ALI using computer algorithms: (i) restrictive definition (definite cases) and (ii) broad definition (definite and probable cases). Patients presenting prior liver conditions were excluded. Manual review of potential cases was performed to confirm diagnosis, in a sample in CPRD (21 %) and all potential cases in BIFAP. Incidence rates of ALI by age, sex and calendar year were calculated.


In BIFAP, all cases considered definite after manual review had been detected with the computer algorithm as potential cases, and none came from the non-cases group. The restrictive definition of ALI had a low sensitivity but a very high specificity (95 % in BIFAP) and showed higher rates of agreement between computer search and manual review compared to the broad definition. Higher incidence rates of definite ALI in 2008 were observed in BIFAP (3.01 (95 % confidence interval (CI) 2.13–4.25) per 100,000 person-years than CPRD (1.35 (95 % CI 1.03–1.78)).


This study shows that it is feasible to identify ALI cases if restrictive selection criteria are used and the possibility to review additional information to rule out differential diagnoses. Our results confirm that idiopathic ALI is a very rare disease in the general population. Finally, the construction of a standard definition with predefined criteria facilitates the timely comparison across databases.


Primary care databases Incidence Acute liver injury Computer algorithms Diagnosis definition BIFAP CPRD 



We thank Dr Lucia Cea-Soriano for reviewing previous version of the manuscript. The research leading to these results was conducted as part of the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT; which is a public-private partnership coordinated by the European Medicines Agency. Authors would like to thank the excellent collaboration of physicians in the participating countries, whose contribution in recording their professional practice with high-quality standards makes possible the availability of databases used in this research.


The PROTECT project has received support from the Innovative Medicines Initiative Joint Undertaking ( under Grant Agreement no. 115004, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in-kind contribution. In the context of the IMI Joint Undertaking (IMI JU), the Department of Pharmacoepidemiology, Utrecht University, received a direct financial contribution from Pfizer. The views expressed are those of the authors only.

Authorship statement

Guarantor of article: Ana Ruigómez

Specific author contributions

Ruigomez A, Garcia Rodriguez LA designed the research study and wrote the protocol.

Ruigomez A, Brauer R and Requena G performed the computer research and analyzed the data.

Ruigomez A, Garcia Rodriguez LA, Brauer R and Bate A drafted the manuscript.

Huerta C, Francisco de Abajo, Requena G and Gil M collected and managed the data in BIFAP and reviewed the manuscript.

Brauer R, Downey G and Feudjo Tepie M collected and managed the data in CPRD.

de Groot M, Schlienger R, Reynolds R and Klungel O reviewed the protocol and manuscript.

All authors contributed to the study design discussions, revising the manuscript, and given the approval of final versions.

Supplementary material

228_2014_1721_MOESM1_ESM.pdf (59 kb)
Online resource 1 (PDF 59 kb)
228_2014_1721_MOESM2_ESM.pdf (94 kb)
Online resource 2 (PDF 93 kb)
228_2014_1721_MOESM3_ESM.pdf (65 kb)
Online resource 3 (PDF 64 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • A. Ruigómez
    • 1
    Email author
  • R. Brauer
    • 2
    • 5
  • L. A. García Rodríguez
    • 1
  • C. Huerta
    • 3
  • G. Requena
    • 3
  • M. Gil
    • 3
  • Francisco de Abajo
    • 3
    • 4
  • G. Downey
    • 5
  • A. Bate
    • 6
  • M. Feudjo Tepie
    • 5
  • M. de Groot
    • 7
  • R. Schlienger
    • 8
  • R. Reynolds
    • 9
  • O. Klungel
    • 7
  1. 1.Centro Español de Investigación Farmacoepidemiologica (CEIFE)MadridSpain
  2. 2.Faculty of Epidemiology and Population HealthLondon School of Hygiene and Tropical MedicineLondonUK
  3. 3.Division of Pharmacoepidemiology and Pharmacovigilance, Medicines for Human Use DepartmentAgencia Española de Medicamentos y Productos Sanitarios (AEMPS)MadridSpain
  4. 4.Pharmacology Section, Department of Biomedical Sciences IIUniversity of AlcaláMadridSpain
  5. 5.Amgen NVLondonUK
  6. 6.EpidemiologyPfizer LtdTadworthUK
  7. 7.Division of Pharmacoepidemiology & Clinical Pharmacology, Faculty of ScienceUtrecht UniversityUtrechtThe Netherlands
  8. 8.Novartis Pharma AGBaselSwitzerland
  9. 9.EpidemiologyPfizer Research & DevelopmentNew YorkUSA

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