Gisbert Javier P, Luna Marta, González-Lama Yago, Pousa Inés D, Velasco Marta, Moreno-Otero Ricardo, Maté José
Gastroenterology Unit, Hospital Universitario de la Princesa, Universidad Autónoma, Madrid, Spain.
Inflamm Bowel Dis. 2007 Sep;13(9):1106-14. doi: 10.1002/ibd.20160.
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.
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.
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 These drugs were withdrawn due to hepatotoxicity (LTs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.
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.
本研究旨在评估一大群炎症性肠病（IBD）患者肝功能检查（LTs）异常或肝毒性的发生率，特别是在一项长期随访研究中评估硫唑嘌呤（AZA）/巯嘌呤（MP）引起的肝损伤发生率。
本回顾性研究纳入了所有连续随访至少5年的IBD患者。定期监测包括丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转移酶和胆红素在内的肝功能检查指标。“肝功能检查异常”定义为肝功能检查指标在正常范围上限（N）至2N之间，“肝损伤/肝毒性”定义为肝功能检查指标>2N。
共纳入786例患者，其中138例接受AZA/MP治疗；随访期间，分别有120例患者（15%）和39例患者（5%）出现肝功能检查异常或肝毒性。最常见的原因是AZA/MP治疗和脂肪性肝病。在接受AZA/MP治疗的患者中（随访690患者年），肝功能检查异常和肝毒性的发生率分别为每年7.1%和2.6%。尽管继续使用AZA/MP，大多数患者的肝功能检查指标仍自发恢复正常。3.6%的患者因肝毒性（肝功能检查指标>5N且在剂量降低50%后仍未下降）停用这些药物，所有患者的肝功能检查指标均恢复正常。
在IBD患者中，AZA或MP治疗在相当比例的病例中会导致肝功能检查异常，但真正的肝毒性/肝损伤情况罕见。此外，IBD患者中大多数硫唑嘌呤诱导的肝毒性病例较轻，尽管继续使用AZA/MP，肝功能检查指标异常仍会自发恢复正常，仅约4%的患者需要停药。
