Incidence, risk factors and clinical course of thiopurine-induced liver injury in patients with inflammatory bowel disease.
BACKGROUND
The incidence of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease varies in different studies.


OBJECTIVE
To assess the rate of thiopurine-induced liver toxicity in patients with inflammatory bowel disease; to determine the predictive factors and to characterize its clinical course and management.


METHODS
A cohort of 161 patients was prospectively followed for a median of 271 days. Hepatotoxicity was established when alanine transaminase or alkaline phosphatase plasma levels were greater than twice the upper normal limit.


RESULTS
Abnormal liver function was detected in 21 patients (13%; 95% CI: 7-18). Hepatotoxicity occurred in 16 patients (10%; 95% CI: 6-16) after a median of 85 days. In five cases, treatment was withdrawn due to hepatotoxicity. Use of corticosteroids was associated with hepatotoxicity (OR: 4.94; 95% CI: 1.01-23.98) with antitumour necrosis factor concomitant therapy showing a protective role (OR: 0.3; 95% CI: 0.1-3.1). gamma-Glutamyl transferase plasma levels at the onset of hepatotoxicity showed the best predictive value for treatment withdrawal (area under the receiver operating characteristic curve: 0.95).


CONCLUSIONS
The incidence of hepatotoxicity in inflammatory bowel disease patients receiving thiopurines is relevant, mainly in patients co-treated with corticosteroids. gamma-Glutamyl transferase plasma level is a useful biomarker in therapy withdrawal prediction.
Bastida
G
G
Gastroenterology Unit, La Fe Hospital, Valencia, Spain. gbastidap@sepd.org
Nos
P
P
Aguas
M
M
Beltrán
B
B
Rubín
A
A
Dasí
F
F
Ponce
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects; D015415:Biomarkers / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D008107:Liver Diseases / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine