Outcome of acute idiosyncratic drug-induced liver injury:... : Hepatology (original) (raw)

Liver Failure and Liver Disease: Liver Disease

Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry

Andrade, Raúl J.1,*; Lucena, Isabel M.2; Kaplowitz, Neil3; García-Muņoz, Beatriz1; Borraz, Yolanda4; Pachkoria, Ketevan4; García-Cortés, Miren1; Fernández, Carmen M.5; Pelaez, Gloria6; Rodrigo, Luis6; Durán, José A.6; Costa, Joan7; Planas, Ramón8; Barriocanal, Anabel7; Guarner, Carlos9; Romero-Gomez, Manuel10; Muņoz-Yagüe, Teresa11; Salmerón, Javier12; Hidalgo, Ramón13

1_Unidad de Hepatología, Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Co-ordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain_

2_Servicio de Farmacología Clínica, Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos, Co-ordinating Centre, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain_

3_Research Center for Liver Disease, Keck School of Medicine, University of Southern California, Los Angeles, CA_

4_Departamento de Farmacología, Facultad de Medicina, Campus Universitario de Teatinos s/n, Málaga, Spain_

5_Servicio de Farmacología Clínica, Hospital Torrecárdenas, Almeria, Spain_

6_Servicio Aparato Digestivo, Hospital Torrecárdenas, Almeria, Spain_

7_Servicio de Farmacología Clínica, Hospital Germans Trias i Pujol, Barcelona, Spain_

8_Servicio Aparato Digestivo, Hospital Germans Trias i Pujol, Barcelona, Spain_

9_Servicio Aparato Digestivo, Hospital Sant Pau, Barcelona, Spain_

10_Servicio Aparato Digestivo, Hospital Valme, Sevilla, Spain_

11_Servicio Aparato Digestivo, Hospital 12 de Octubre, Madrid, Spain; Javier Salmerón_

12_Servicio Aparato Digestivo, Hospital Clínico S Cecilio, Granada, Spain_

13_Centro de Cálculo, Universidad de Málaga, Málaga, Spain_

*Unidad de Hepatología, Departamento de Medicina, Facultad de Medicina, Boulevard Louis Pasteur, 32 Campus de Teatinos s/n, 29071 Málaga, Spain

Email:[email protected]

Received 18 May 2006; Accepted 22 September 2006

Published online in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: Agencia Espaņola del Medicamento; Grant sponsor: Fondo Investigaciones Sanitarias; Grant Number: FIS #04-1688.

The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the manuscript for publication.

Potential conflict of interest: Nothing to report.

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Abstract

A chronic adverse reaction may occur in some instances of drug-induced liver injury (DILI), even despite drug cessation. In our study, we obtained records from a Spanish registry and evaluated cases of DILI with biochemical evidence of long-term damage. Chronic outcome was defined as a persistent biochemical abnormality of hepatocellular pattern of damage more than 3 months after drug withdrawal or more than 6 months after cholestatic/mixed damage. Data on 28 patients with a chronic clinical evolution (mean follow-up 20 months) between November 1995 and October 2005 were retrieved (18 female; overall mean age 55 yr) and accounted for 5.7% of total idiosyncratic DILI cases (n = 493) submitted to the registry. The main drug classes were cardiovascular and central nervous system (28.5% and 25%, respectively), which, in contrast, represented only 9.8% and 13%, respectively, of all DILI cases. The most frequent causative drugs were amoxicillin–clavulanate (4 of 69 cases), bentazepam (3 of 7 cases), atorvastatin (2 of 7 cases), and captopril (2 of 5 cases). Patients with cholestatic/mixed injury (18 of 194 cases [9%]) were more prone to chronicity than patients with hepatocellular injury (10 of 240 cases; P < .031). In the case of chronic hepatocellular injury, 3 patients progressed to cirrhosis and 2 to chronic hepatitis. In the cholestatic/mixed group, liver biopsy indicated cirrhosis in 1 patient and ductal lesions in 3 patients. In conclusion , cholestatic/mixed type of damage is more prone to become chronic while, in the hepatocellular pattern, the severity is greater. Cardiovascular and central nervous system drugs are the main groups leading to chronic liver damage.