Duvoux C, Kracht M, Lang P, Vernant J P, Zafrani E S, Dhumeaux D
Service d'Hépatologie et de Gastroentérologie, Hôpital Henri-Mondor, Créteil.
Gastroenterol Clin Biol. 1991;15(12):968-73.
Three cases of nodular regenerative hyperplasia of the liver associated with azathioprine therapy are reported. The indication of azathioprine differed in each of the 3 cases including kidney transplantation, graft-versus-host disease following bone marrow transplantation, and suspicion of bowel inflammatory disease, respectively. In all three patients, nodular regenerative hyperplasia was discovered after a prolonged administration of azathioprine (24 to 40 months), with a cumulative dose of 52 to 120 g. Under light microscopy, vascular lesions were associated with nodular regenerative hyperplasia in the 3 cases and consisted of sinusoidal dilatation (2 cases), perisinusoidal fibrosis (2 cases), and peliosis (1 case). In two patients, nodular regenerative hyperplasia was responsible for severe portal hypertension which was treated by portacaval shunt. These findings are strongly suggestive of a role of azathioprine in the occurrence of nodular regenerative hyperplasia. The mechanism of azathioprine-induced nodular regenerative hyperplasia could be related to sinusoidal lesions caused by azathioprine and responsible for liver hypoperfusion, with regenerative hyperplasia in the areas remaining normally perfused. Patients receiving long-term therapy with azathioprine should be followed-up regularly and liver biopsy should be performed when clinical or biochemical liver abnormalities are observed.
报告了3例与硫唑嘌呤治疗相关的肝脏结节性再生性增生病例。3例患者使用硫唑嘌呤的指征各不相同，分别为肾移植、骨髓移植后的移植物抗宿主病以及疑似肠道炎症性疾病。在所有3例患者中，硫唑嘌呤长期使用（24至40个月）后发现结节性再生性增生，累积剂量为52至120克。在光学显微镜下，3例患者的血管病变与结节性再生性增生相关，包括窦性扩张（2例）、窦周纤维化（2例）和肝紫癜（1例）。2例患者中，结节性再生性增生导致严重门静脉高压，通过门腔分流术进行治疗。这些发现强烈提示硫唑嘌呤在结节性再生性增生的发生中起作用。硫唑嘌呤诱导结节性再生性增生的机制可能与硫唑嘌呤引起的窦性病变有关，导致肝脏灌注不足，而在正常灌注区域出现再生性增生。接受硫唑嘌呤长期治疗的患者应定期随访，当观察到临床或生化肝脏异常时应进行肝活检。
