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Hepatocellular Carcinoma


Figure 2: Model for the Pathogenesis of Hepatocellular Carcinoma in Crohn’s Disease Patients


Crohn’s disease


and two of 10 CD patients treated with azathioprine and infliximab developed HCC (see Table 1).6,10


The accumulation of further cases will be


necessary to clarify the association between infliximab therapy and the development of HCC.


Clinical Significance of Surveying Liver Tumor in Crohn’s Disease Patients


Azathioprine therapy


?


Inflixamab therapy


Focal hepatocyte glycogenosis


It should be stressed that the prognosis for HCC in CD patients without chronic liver disease is poor. Since the majority of cases of HCC in CD patients are thought to be associated with azathioprine therapy, CD patients with prolonged azathioprine therapy should be surveyed for HCC. In addition, CD patients treated with infliximab should be surveyed for HCC as well as hepatosplenic T-cell lymphoma. Since most of the HCC cases showed elevated serum AFP or PIVKA II, evaluation of serum tumor markers and clinical imaging modalities can be useful.


Hepatocellular carcinoma


Conclusion Infliximab Therapy


Infliximab, a monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha), was reported recently to be associated with hepatosplenic T-cell lymphoma in CD patients.18


Infliximab is used widely in CD patients,


1. Juillerat P, Mottet C, Pittet V, et al., Extraintestinal manifestations of Crohn’s disease, Digestion, 2007;76:141–8.


2. Lee FL, Murray SM, Prior J, Shreeve DR, Primary liver cell cancer occurring in association with Crohn’s disease treated with prednisolone and azathioprine, Hepatogastroenterology, 1983;30:188.


3. Cattan S, Wendum D, Chazouilleres O, et al., Hepatocellular carcinoma and focal hepatic glycogenosis after prolonged azathioprine therapy, Hum Pathol, 2000;31:874–6.


4. Borum M, Unusual development of hepatocellular carcinoma in a patient with Crohn’s disease, Dig Dis Sci, 2001;46:2199–200.


5. Oya H, Sato Y, Yamamoto S, et al., Living related donor liver transplantation for primary sclerosing cholangitis with hepatocellular carcinoma and Crohn’s disease: A case report, Transplant Proc, 2004;36:2297–8.


6. Chen SC, Cummings OW, Hartley MP, et al., Hepatocellular carcinoma occurring in a patient with Crohn’s disease treated with both azathioprine and infliximab, Dig Dis Sci, 2006;51:952–5.


7. Demarchi B, Bresso F, Novero D, et al., Hepatocellular carcinoma complicating primary sclerosing cholangitis in


The occurrence of HCC in CD patients without chronic liver disease is exceptional. Although the precise mechanism driving the development of HCC in CD patients is controversial, azathioprine therapy and FHG (and possibly infliximab therapy) are likely to be involved (see Figure 2). Because the prognosis of HCC in CD patients is poor, we stress the importance of surveying CD patients with prolonged azathioprine therapy for liver tumors using a combination of serum tumor markers and clinical imaging modalities. n


Crohn’s disease. A case report, Minerva Gastroenterol Dietol, 2007;53:279–83.


8. Samarasena J, Borgaonkar M, Development of hepatocellular carcinoma in a patient with Crohn’s disease treated with azathioprine, Dig Dis Sci, 2007;52:2748–50.


9. Miura H, Kawaguchi T, Takazoe M, et al., Hepatocellular carcinoma and Crohn’s disease: A case report and review, Inter Med, 2009;48:815–9.


10. Murakami A, Tanaka Y, Ueda M, et al., Hepatocellular carcinoma occurring in a young Crohn’s disease patient, Pathol Int, 2009;59:492–6.


11. Ishida M, Naka S, Shiomi H, et al., Hepatocellular carcinoma occurring in a Crohn’s disease patient, World J Gastroenterol, 2010;16:3215–8.


12. Kandiel A, Fraser AG, Korelitz BI, et al., Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine, Gut, 2005;54:1121–5.


13. Ingvar A, Smedby KE, Lindelöf B, et al., Immunosuppressive treatment after solid organ transplantation and risk of post-transplant cutaneous squamous cell carcinoma,


Nephrol Dial Transplant, 2010;25:2764–71.


14. Gruber S, Dehner LP, Simmons RL, De novo hepatocellular carcinoma without chronic liver disease but with 17 years of azathioprine immunosuppression, Transplantation, 1987;43:597–600.


15. Russmann S, Zimmermann A, Krähenbühl S, et al., Veno- occlusive disease, nodular regenerative hyperplasia and hepatocellular carcinoma after azathioprine treatment in a patient with ulcerative colitis, Eur J Gastroenterol Hepatol, 2001;13:287–90.


16. Arber N, Zajicek G, Nordenberg J, Sidi Y, Azathioprine treatment increases hepatocyte turnover, Gastoenterology, 1991;101:1083–6.


17. Terasaki S, Kaneko S, Kobayashi K, et al., Histological features predicting malignant transformation of nonmalignant hepatocellular nodules: a prospective study, Gastroenterology, 1998;115:1216–22.


18. Rosh JR, Gross T, Mamula P, et al., Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn’s disease: a cautionary tale?, Inflamm Bowel Dis, 2007;13:1024–30.


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US GASTROENTEROLOGY & HEPATOLOGY REVIEW


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