The natural history of histologically proved drug induced liver disease

P G Aithal, C P Day

Centre for Liver Research, The Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK

Correspondence to: Dr Day.

Accepted for publication 17 December 1998

BACKGROUNDThe long term outcome of drug related liver disease is unknown.
AIMSTo study the natural history of histologically proved drug induced hepatotoxicity.
METHODS110 patients with liver biopsies coded either as drug induced liver disease or hepatitis/cholestasis of unknown aetiology were identified from hospital records 1978-1996. Review of case notes and histology identified 44 patients with definite drug induced hepatotoxicity. Forty surviving patients were invited to attend a follow up clinic. History, examination, full liver screen, and isotope and ultrasound liver scans were repeated in all patients. Repeat liver biopsies were offered to patients with abnormal liver tests.
RESULTSPresentation at index biopsy was jaundice in 24 patients, abnormal liver tests in 17, and hepatic failure in three. Antibiotics (n=13) and non-steroidal anti-inflammatory drugs (n=11) were the most common drugs implicated. Initial histology showed acute hepatitis in six, chronic hepatitis in 20, and cholestasis in 18. At 1-19 years (median 5 years) follow up, 13/33 (39%) patients had persistent significant abnormalities in their liver blood tests and/or scans. Three of the five repeat liver biopsies performed showed significant abnormalities. Factors predicting persistence or development of chronic liver disease were fibrosis and continued exposure to the drug.
CONCLUSIONSDrugs should be considered in the differential diagnosis of abnormal liver function and/or histology, as failure to withdraw the offending drug is associated with a high risk of persistent liver damage.
(Gut 1999;44:731-735)

Keywords: drugs;  chronic active hepatitis;  toxic hepatitis;  diclofenac