Abstract
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.
Similar content being viewed by others
References
Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–8.
Farrell GC. Drugs and steatohepatitis. Semin Liver Dis. 2002;22:185–94.
Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–74.
Ludwig J, McGill DB, Lindor KD. Review: nonalcoholic steatohepatitis. J Gastroenterol Hepatol. 1997;12:398–403.
Brunt EM. Pathology of nonalcoholic steatohepatitis. Hepatol Res. 2005;33:68–71.
Babany G, Uzzan F, Larrey D, Degott C, Bourgeois P, Rene E, et al. Alcoholic-like liver lesions induced by nifedipine. J Hepatol. 1989;9:252–5.
Itoh S, Igarashi M, Tsukada Y, Ichinoe A. Nonalcoholic fatty liver with alcoholic hyalin after long-term glucocorticoid therapy. Acta Hepatogastroenterol (Stuttg). 1977;24:415–8.
Langman G, Hall PM, Todd G. Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury. J Gastroenterol Hepatol. 2001;16:1395–401.
Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.
Aapro MS, Martin C, Hatty S. Gemcitabine—a safety review. Anticancer Drugs. 1998;9:191–201.
Cortes-Funes H, Martin C, Abratt R, Lund B. Safety profile of gemcitabine, a novel anticancer agent, in non-small cell lung cancer. Anticancer Drugs. 1997;8:582–7.
Dobbie M, Hofer S, Oberholzer M, Herrmann R. Veno-occlusive disease of the liver induced by gemcitabine. Ann Oncol. 1998;9:681.
Robinson K, Lambiase L, Li J, Monteiro C, Schiff M. Fatal cholestatic liver failure associated with gemcitabine therapy. Dig Dis Sci. 2003;48:1804–8.
Coeman DC, Verbeken EK, Nackaerts KL, Demedts MG, Vansteenkiste JF. A fatal case of cholestatic liver failure probably related to gemcitabine. Ann Oncol. 2000;11:1503.
Kagohashi K, Funayama Y, Satoh H, Sekizawa K. Fatal hepatic failure due to gemcitabine and vinorelbine. Ann Oncol. 2003;14:960.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ren, X.S., Harada, K., Yoshikawa, S. et al. A fatal case of progressive steatohepatitis, possibly chemotherapy-associated steatohepatitis related to gemcitabine. Clin J Gastroenterol 3, 191–194 (2010). https://doi.org/10.1007/s12328-010-0159-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12328-010-0159-8