A fatal case of progressive steatohepatitis, possibly chemotherapy- associated steatohepatitis related to gemcitabine

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We report the case of an 80-year-old female suffering from pancreatic cancer who developed severe non-alcoholic steatohepatitis (NASH) resulting in fatal hepatic failure after anti-cancer chemotherapy with gemcitabine. Hepatic encephalopathy appeared 1 year after the chemotherapy, and the patient developed progressive liver failure and eventually died. Radiological examination showed severe fatty liver. Histopathological examination of a liver needle necropsy showed almost panlobular macrovesicular fatty change. Ballooning degeneration and necrosis of hepatocytes accompanying neutrophil infiltration, Mallory bodies, and a few bile plugs were found in zone 3. Marked perivenular and pericellular/perisinusoidal fibrosis and extensive bridging fibrosis were also found. Together, these findings indicated steatohepatitis at a precirrhotic stage. Because the patient had no history of drinking in excess, we made a diagnosis of NASH, in particular, chemotherapy-associated steatohepatitis (CASH). Gemcitabine is a pyrimidine nucleoside antimetabolite with anti-cancer activity. A few reports have mentioned fatal hepatotoxicity caused by gemcitabine, but, to our knowledge, this is the first report of steatohepatitis, possibly associated with gemcitabine. Physicians treating patients with this drug should be aware of the possibility of steatohepatitis. © Springer 2010.