Nodular regenerative hyperplasia has not previously been reported in p
atients who have undergone orthotopic liver transplantation. In this r
eport we describe the clinical, biochemical and histologic findings in
nine liver transplant recipients in whom nodular regenerative hyperpl
asia developed between 6 and 144 mo (median, 64 mo) after transplantat
ion. Six of the patients manifested features of portal hypertension (v
ariceal bleeding, ascites, severe intractable peripheral edema), where
as three patients were asymptomatic at the time of diagnosis. All pati
ents had elevated serum alkaline phosphatase (median, 269 IU; range, 1
59 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 o
f venous outflow block, consistent with azathioprine hepatotoxicity. A
h nine patients had been taking azathioprine up to the time of present
ation. After withdrawal of azathioprine, liver function tests improved
appreciably in five patients and histologic improvement was documente
d in four of these who underwent follow-up liver biopsies. In the rema
ining four patients progressive graft failure ensued and all subsequen
tly underwent repeat liver retransplantation. At a certain stage, nodu
lar regenerative hyperplasia, in the context of a liver graft, becomes
an irreversible lesion, emphasizing the need for early identification
and withdrawal of the agent.