INTRODUCTION: Acute hepatic failure is rarely caused by metastatic cancer. We present a case of acute hepatic failure due to infiltrating small cell carcinoma.
CASE PRESENTATION: A 55 year-old female presented with abdominal discomfort and nausea. The patient denied constitutional symptoms, shortness of breath, cough, hemoptysis, or chest pain. Her medical history was significant for Crohn's disease controlled with infliximab and azathioprine, prior small bowel obstructions, and chronic kidney disease. She had smoked daily for forty years and denied alcohol, drugs or other ingestions. She had mild jaundice and cachecia. Her abdomen was mildly distended, tympanitic, but soft and non-tender. Laboratory analysis revealed lactic acidosis, macrocytosis and elevated liver associated enzymes (AST 224, ALT 90, total bilirubin 2.5). Her coagulation parameters were normal. Portable chest x-Ray was unremarkable. Abdominal ultrasound revealed a nodular hepatic border without focal mass. Hepatic and portal venous blood flows were normal. CT-Abdomen showed no focal masses or lymphadenopathy. She subsequently deteriorated with development of hepatic encephalopathy, worsening lactic acidosis, transaminitis, and eventual respiratory failure and hepatorenal syndrome. Of note, her LDH was 8625 and her uric acid was 15. Viral and autoimmune serologies and toxin screens were negative. In anticipation of urgent referral for liver transplantation, liver biopsy was performed to confirm suspected drug induced hepatitis. Instead it revealed diffuse infiltrating small cell carcinoma. Chemotherapy was offered, however, the patients family elected to withdraw care.
DISCUSSION: Acute hepatic failure is diagnosed when severe complications of liver disease develop within four weeks of initial presentation. Most common etiologies are viral hepatitis, drug toxicity, ischemia, or vascular thrombosis. However, some studies suggest up to forty percent of cases are not identified prior to death. Malignancy causing acute hepatic failure is exceedingly rare, but must be considered due to implications on treatment and to avoid inappropriate referral for transplantation. Malignancies reported to cause acute hepatic failure include lymphoma, breast, lung, melanoma, colorectal and pancreatic carcinoma. Small cell carcinoma is more common than non-small cell lung cancers. Infiltrating small cell carcinoma is universally fatal. Onset of jaundice to death averages ten days. The longest reported time of survival with hepatic failure due to small cell carcinoma was six months with chemotherapy. Possible mechanisms include massive cytokine release, damage of bile ducts, compression of sinusoids leading to ischemia, tumor replacement of hepatocytes, and tumor emboli compromising the portal system. Severe elevations in lactate dehydrogenase and uric acid are typical. The ratio of LDH to ALT is significantly elevated when compared to non-malignant hepatic failure. Radiologic evaluation is typically nonspecific. The cerebral edema of fulminate hepatic failure has not been seen in cases of malignancy related hepatic failure. Small cell carcinoma has sub-fulminant liver involvement in 22-29% of cases at time of diagnosis. The usual appearance is macroscopic nodules with possible patchy infiltration. Currently, there are less than twenty reported cases of fulminant hepatic failure due to small cell infiltration. Interestingly, most cases do not show any suspect lesions on chest x-ray. Biopsy usually shows diffuse hepatic parenchymal replacement or sinusoidal infiltration.
CONCLUSIONS: Malignant infiltration of the liver is a rare cause of fulminant hepatic failure but must be considered due to implications for treatment and transplantation. Radiologic studies are nonspecific. Clues include elevated LDH, uric acid, and LDH/ALT ratio. Biopsy must be performed, the earlier the better. While infiltrating small cell carcinoma is universally fatal, survival has been seen with non-Hodgkin’s Lymphoma.
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Reference #2 McGuire, Brendan. Small Cell Carcinoma of the lung manifesting as acute hepatic failure. Mayo clinic Proceedings, 72 133-139, 1997
Reference #3 Rajvanshi, Pankaj. Fulminant heptic failure secondary to neoplastic infiltration of the liver. J. of clinical gasteroenterology 39; 339-341, 2005
DISCLOSURE: The following authors have nothing to disclose: Scott Hagedorn, William Kelly
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