The natural history of histologically proved drug induced liver disease
P G Aithal 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
BACKGROUND Keywords:
drugs;
chronic active hepatitis;
toxic hepatitis;
diclofenac
The long term outcome of
drug related liver disease is unknown.
AIMS
To study the natural history
of histologically proved drug induced hepatotoxicity.
METHODS
110 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.
RESULTS
Presentation 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.
CONCLUSIONS
Drugs 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)
© 1999 by Gut
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