title: Outcome of acute idiosyncratic drug-induced liver injury: Long-term follow-up in a hepatotoxicity registry.
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.
authors.affiliation: 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. andrade@uma.es
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Andrade
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Lucena
authors.forename: Neil
authors.initials: N
authors.lastname: Kaplowitz
authors.forename: Beatriz
authors.initials: B
authors.lastname: García-Muņoz
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Borraz
authors.forename: Ketevan
authors.initials: K
authors.lastname: Pachkoria
authors.forename: Miren
authors.initials: M
authors.lastname: García-Cortés
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Fernández
authors.forename: Gloria
authors.initials: G
authors.lastname: Pelaez
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: José A
authors.initials: JA
authors.lastname: Durán
authors.forename: Joan
authors.initials: J
authors.lastname: Costa
authors.forename: Ramón
authors.initials: R
authors.lastname: Planas
authors.forename: Anabel
authors.initials: A
authors.lastname: Barriocanal
authors.forename: Carlos
authors.initials: C
authors.lastname: Guarner
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gomez
authors.forename: Teresa
authors.initials: T
authors.lastname: Muņoz-Yagüe
authors.forename: Javier
authors.initials: J
authors.lastname: Salmerón
authors.forename: Ramón
authors.initials: R
authors.lastname: Hidalgo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects; D000069059:Atorvastatin; D001381:Azepines / Q000009:adverse effects; D002216:Captopril / Q000009:adverse effects; D002317:Cardiovascular Agents / Q000009:adverse effects; D002491:Central Nervous System Agents / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury; D002908:Chronic Disease; D018450:Disease Progression; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000009:adverse effects; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008107:Liver Diseases / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects; D012042:Registries; D013030:Spain / Q000453:epidemiology
chemical_list: D001381:Azepines; D002317:Cardiovascular Agents; D002491:Central Nervous System Agents; D006538:Heptanoic Acids; D011758:Pyrroles; C006129:bentazepam; D019980:Amoxicillin-Potassium Clavulanate Combination; D002216:Captopril; D000069059:Atorvastatin