Nodular regenerative hyperplasia of the liver graft after liver transplantation

Nodular regenerative hyperplasia has not previously been reported in patients who have undergone orthotopic liver transplantation. In this report we describe the clinical, biochemical and histologic findings in nine liver transplant recipients in whom nodular regenerative hyperplasia developed between 6 and 144 mo (median, 64 mo) after transplantation. Six of the patients manifested features of portal hypertension (variceal bleeding, ascites, severe intractable peripheral edema), whereas three patients were asymptomatic at the time of diagnosis. All patients had elevated serum alkaline phosphatase (median, 269 IU; range, 159 to 1182 IU) and gamma-glutamyl transferase levels (median, 247 IU; range 104 to 1513 IU). Other liver function tests remained normal. In five patients, earlier biopsies had identified histological features of venous outflow block, consistent with azathioprine hepatotoxicity. All nine patients had been taking azathioprine up to the time of presentation. After withdrawal of azathioprine, liver function tests improved appreciably in five patients and histologic improvement was documented in four of these who underwent follow-up liver biopsies. In the remaining four patients progressive graft failure ensued and all subsequently underwent repeat liver retransplantation. At a certain stage, nodular regenerative hyperplasia, in the context of a liver graft, becomes an irreversible lesion, emphasizing the need for early identification and withdrawal of the agent.