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 grou Z p of inflammatory bowel disease (1131)) 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 1131) patients followed for at least 5 years were included in this retrospective study. LTs including alanine transaminase, aspartate transaminase, alkaline phosphatase, y-glutamyl transferase, and bilirubin were periodically monitored. "Abnormality-of-l-Ts" was defined as LTs between N (upper limit of the normal range) and 2 N, and "liver injury/hepatotoxicity" as LTs >2 N. Z:) 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 followup) 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 These drugs were withdrawn due to hepatotoxicity (LTs 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 1131) 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 1131) patients are mild, and the abnormalities in LTs spontaneously return to normal values despite AZA/MP being maintained, therapy withdrawal being necessary in only approximate to 4% of the patients.