Autoimmune Hepatitis - Overlap Syndrome (AH) occurring during imatinib therapy in a gastro-intestinal stromal tumor (GIST) patient

Abstract

9064 Background. AH is a chronic hepatitis of unknown etiology characterized by hyperglobulinemia, circulating autoantibodies (AA) and at least piecemeal necrosis on liver histology. GISTs are rare tumors in which the occurence of paraneoplastic disease have never been reported (National Library of Medicine). We describe the development of a chronic hepatitis in an Imatinib responsive GIST patient. Methods. A 65-year-old caucasian male presented with a GIST peritoneal spread. No signs of liver involvement were evident at CT and MRI. Liver function (aminotransferases, bilirubin, alkaline phosphatase and glutamyltranspeptidase) was normal. The patient was started on Imatinib 400 mg daily. A partial response was achieved after two months of treatment. At that time a progressive increase of aminotransferases (AST and ALT) without any other clinical sign of liver toxicity or GIST progression was detected. Liver infections, drug abuse and metabolic diseases were excluded. Autoantibodies were present therefore a liver biopsy was performed. Results. ANA and AMA-2 positivity was respectively weak and strong. Histology showed: interface hepatitis with piecemeal necrosis with lobular involvement, bridging necrosis and lymphocyte infiltrate. Prednisone (1mg/kg) prompted a progressive ALT reduction from 1056 U/L to normal value. Imatinib was concurrently restarted without any problem, leading to further GIST lesion reduction. Conclusions. A moderate increase of ALT is a well recognized and reversible Imatinib toxicity. In the occurence of increasing ALT value, regardless of Imatinib interruption, clinicians should be aware of AH. AH is responsive to steroid therapy and does not require to stop Imatinib for full recovery. No significant financial relationships to disclose.