Liver injury in inflammatory bowel disease: long-term follow-up study of 786 patients.
BACKGROUND
The aim of the study was to evaluate the incidence of abnormality of liver tests (LTs) or hepatotoxicity in a large group of inflammatory bowel disease (IBD) patients and, specifically, to assess the incidence of azathioprine (AZA)/mercaptopurine (MP)-induced liver injury in a long-term follow-up study.


METHODS
All consecutive IBD patients followed for at least 5 years were included in this retrospective study. LTs including alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin were periodically monitored. "Abnormality-of-LTs" was defined as LTs between N (upper limit of the normal range) and 2 N, and "liver injury/hepatotoxicity" as LTs>2 N.


RESULTS
A total of 786 patients were included, and 138 received AZA/MP; 120 patients (15%) and 39 (5%) presented abnormality of LTs or hepatotoxicity, respectively, during follow-up. The most frequent explanations were AZA/MP treatment and fatty liver disease. Among AZA/MP-treated patients (690 patient-years follow-up) the incidence of abnormal LTs and hepatotoxicity was, respectively, 7.1% and 2.6% per patient-year. Most patients spontaneously normalized LTs despite maintaining AZA/MP. These drugs were withdrawn due to hepatotoxicity (LTs>5 N and lack of decrease despite 50% dose reduction) in 3.6% of the patients and all of them normalized LTs.


CONCLUSIONS
In IBD patients, AZA or MP treatment induces abnormality of LTs in a relatively high proportion of the cases, but the development of true hepatotoxicity/liver injury is exceptional. Moreover, most of the cases of thiopurine-induced hepatotoxicity in IBD patients are mild, and the abnormalities in LTs spontaneously return to normal values despite AZA/MP being maintained, therapy withdrawal being necessary in only approximately 4% of the patients.
Gisbert
Javier P
JP
Gastroenterology Unit, Hospital Universitario de la Princesa, Universidad Autónoma, Madrid, Spain. gisbert@meditex.es
Luna
Marta
M
González-Lama
Yago
Y
Pousa
Inés D
ID
Velasco
Marta
M
Moreno-Otero
Ricardo
R
Maté
José
J
D000328:Adult; D000465:Algorithms; D001379:Azathioprine / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D003093:Colitis, Ulcerative / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use / Q000633:toxicity; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D008099:Liver / Q000293:injuries*; D008297:Male; D015122:Mercaptopurine / Q000633:toxicity; D008875:Middle Aged; D013997:Time Factors
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine