2506 A Fatal Case of Gemcitabine-Induced Acute Liver Failure

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INTRODUCTION: Gemcitabine is a common chemotherapeutic agent with broad anti-tumor activity. Gemcitabine induced acute liver failure (ALF) is exceedingly rare, resulting in severe steatohepatosis and high mortality. We report the ninth case of Gemcitabine induced ALF. CASE DESCRIPTION/METHODS: A 65 year-old female on her second cycle of palliative Gemcitabine for metastatic breast cancer presented with five days of weakness, nausea and vomiting after chemotherapy. She was afebrile but hypotensive. She was not visibly jaundiced, sclerae anicteric, and without palpable hepatomegaly. Her initial labs were significant for elevated direct bilirubin, ALP and transaminitis suggestive of a cholestatic pattern (Figure 1). Notably, she had no hepatic dysfunction one month prior to presentation. Ultrasound revealed fatty infiltration of the liver without evidence of obstruction or acute cholecystitis. She developed worsening steatohepatitis with direct bilirubin predominance (Figure 2). CT abdomen revealed fatty replacement of the liver without obstruction or metastasis. Her course was complicated by severe thrombocytopenia, anemia, and renal failure. She deteriorated despite supportive care, becoming increasingly jaundiced and encephalopathic, expiring on hospital day 5. Table 1. DISCUSSION: Chemotherapy agent Gemcitabine is a deoxycitadine analog that incorporates into DNA resulting in apoptosis. Generally well-tolerated, common side effects include myelosuppression and transient elevations in LFTs. However, gemcitabine is implicated as the causative agent of a rare, severe and highly fatal cholestatic ALF. Gemcitabine induced ALF appears idiosyncratic, without clear correlation between dose or duration of treatment. In Gemcitabine induced ALF, imaging shows fatty infiltration of hepatic parenchyma and biopsy reveals hepatocyte ballooning and marked cholestasis. These cases are often rapidly fatal, complicated by thrombocytopenia, coagulopathy and renal failure. Our literature review revealed two cases of patient survival; in one case, Gemcitabine was promptly recognized as the offending agent and high dose steroid therapy was initiated. This may represent a treatment strategy where thus far no others exist. As drug induced hepatotoxicity is the most common cause of ALF in the USA, clinicians should be aware of this hepatotoxic potential, especially given the high mortality rate of Gemcitabine induced ALF.