Veno-occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis.
We report the case of a 66-year-old male with ulcerative colitis diagnosed in 1987, who had been treated with azathioprine (AZA) for the past two years (average dose about 1.6 mg/kg/day). In May 1999 he presented with painless jaundice, fatigue and recent weight loss. Cholestatic enzymes were elevated, alpha-fetoprotein was normal and hepatitis B/C serology negative. After diagnosis of veno-occlusive disease (VOD) and hepatocellular carcinoma (HCC) via biopsy, tumour resection was performed. The histology was typical for a well-differentiated HCC with trabecular and pseudoglandular structures. Neighbouring liver tissue was atrophic, with nodular regenerative hyperplasia (NRH), peliosis-like sinusoidal ectasias and intra-sinusoidal accumulation of blood, associated with peri-sinusoidal fibrosis. Although none of the well-established risk factors for HCC such as cirrhosis, hepatitis B/C, metabolic liver disease or toxins were present, this patient developed HCC. This and previous reports suggest that NRH and/or VOD associated with AZA represent a risk factor for HCC. AZA should therefore not only be stopped in patients with NRH/VOD but patients should also be screened for HCC.
Russmann
S
S
Department of Clinical Pharmacology, Inselspital, University of Berne, Switzerland. stefan.russmann@ikp.unibe.ch
Zimmermann
A
A
Krähenbühl
S
S
Kern
B
B
Reichen
J
J
D000368:Aged; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000473:pathology; D003093:Colitis, Ulcerative / Q000188:drug therapy; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male
D007166:Immunosuppressive Agents; D001379:Azathioprine