Background: Severe clinical hepatitis after imatinib treatment has been reported anecdotally. Hepatic tissue of patients with liver matastasis is often fragile and difficult to handle during liver resection from gastrointestinal stromal tumor (GIST).
Objective: Observe hepatic tissue of these patients and examine the detailed histopathology underlying the change in the texture of non-tumorous hepatic parenchyma of these patients.
Materials and methods:We reviewed six GIST patients with liver metastases who underwent hepatic resection at King Chulalongkorn Memorial Hospital between July 2004 and November 2005. Four patients did not have imatinib and two patients received imatinib for four and eight months before liver resection. Preoperative hepatic biochemistry profiles of all patients were unremarkable. We examined histopathology of non-tumorous hepatic parenchyma of these patients using H-E staining, and additional histochemistry for vascular endothelial growth factor and epidermal growth factor receptor using immunohistochemistry staining.
Results: In all patients, common histopathological changes were swelling of hepatocytes, diffuse parenchymal congestion, dilatation of central vein, and infiltration of portal tract by mononuclear cells. However, there was significant zone 3 hepatocytolysis only in patients who received imatinib treatment. Additionally, moderate degree of hepatic steatosis correlated well with the duration of imatinib exposure. Immunohistochemical study could not demonstrate any difference between these two groups.
Conclusion: In two cases of subclinical hepatotoxicity from exposure to imatinib, histopathologic findings were consistent with drug induced liver injury. Imatinib induced liver injury may be more common than obvious clinical hepatitis.
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1. Demetri GD von Mehren M Blanke CD Van den Abbeele AD Eisenberg B Roberts PJ et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002; 347:472-80.
2. Schwetz BA. New Treatment for Chronic Myelogenous Leukemia. JAMA. 2001; 286:35.
3. Cohen MH Williams G Johnson JR Duan J Gobburu J Rahman A et al. Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res. 2002; 8: 935-42.
4. Ayoub WS Geller SA Tran T Martin P Vierling JM Poordad FF. Imatinib (Gleevec®) induced hepatotoxicity. J Clin Gastroenterol 2005; 39:75-7.
5. Kikuchi S Muroi K Takahashi S Kawano-Yamamoto C Takatoku M Miyazato A et al. Severe hepatitis and complete molecular response caused by imatinib mesylate : possible association of its serum concentration with clinical outcomes. Leuk Lymphoma. 2004; 45:2349-51.
6. Lin NU Sarantopoulos S Stone JR Galinsky I Stone RM Deangelo DJ et al. Fatal hepatic necrosis following imatinib mesylate therapy. Blood. 2003; 102: 3455-6.
7. Ohyashiki K Kuriyama Y Nakajima A Tauchi T Ito Y Miyazawa H et al. Imatinib mesylate-induced hepatotoxicity in chronic myeloid leukemia demonstrated focal necrosis resembling acute viral hepatitis Leukemia. 2002; 16:2160-1.
8. James C Trouette H Marit G Cony-Makhoul P Mahon FX. Histological features of acute hepatitis after imatinib mesylate treatment. Leukemia. 2003; 7:978-9.
9. Pas TDe Danesi R Catania C Curigliano G Braud FDe. Imatinib administration in two patients with liver metastases from GIST and severe jaundice. Br J Cancer. 2003; 89:1403-4.
10. Bauer S Hagen V Pielken HJ Bojko P Seeber S Schutte J. Imatinib mesylate therapy in patients with gastrointestinal stromal tumors and impaired liver function. Anti-Cancer Drugs. 2002; 13:847-9.