[Nodular regenerative hyperplasia of the liver associated with azathioprine therapy]

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.