An Unusual Cause of Acute Liver Failure

Abstract

Diffuse hepatic infiltration by metastases has been recognized as a rare cause of acute liver failure (ALF). ALF due to metastatic transitional cell carcinoma is extremely rare. We report the first case of ALF due to diffuse hepatic infiltration of metastatic transitional cell carcinoma in the US. A 59-year-old man with a history of transitional cell carcinoma of the right ureter (G2, T2, N0, Mx) who underwent complete surgical resection in 07/2004. He failed to follow up with the urology clinic post surgery. One month prior to admission, the patient started to have pruritus all over his body. One week prior to admission, the patient started to have jaundice. He also complained of a vague fullness in the right upper quadrant. Physical examination was significant only for jaundice, multiple excoriations on the skin, and mildly tender hepatomegaly. The laboratory studies were significant for protein 7.6, albumin 2.7, total bilirubin 15, direct bilirubin 12.7, ALT 117, AST 141, alkaline phosphate 1505, and INR 1.3. All the following studies were negative: HAV, HBV, HCV, HIV, ANA, AMA, ASMA, AKLMA, anti-dsDNA. An ultrasound showed hepatomegaly at 18 cm with “diffuse fatty infiltration,” and no intrahepatic or extrahepatic biliary dilatation. A liver biopsy showed multiple clusters of malignant cells in the parenchyma and blood vessels; immunohistochemical stains (CD34 +, D2–40 -, CK7 +, thrombomodulin +, CK20 -) were consistent with metastatic transitional cell carcinoma. The patient rapidly developed encephalopathy and coagulopathy. He deteriorated to multi-organ failure and expired 2 weeks after admission. Metastases to the liver occur mainly as discrete single or multiple lesions. However, in ALF, liver infiltration by tumor cells typically has a diffuse pattern that is often not detected by imaging studies. The release of cytokines from neoplastic cells has been postulated to cause interlobular bile duct destruction and portal fibrosis. The consequence is obstruction of sinusoidal microcirculation and ultimately hepatocyte ischemia and death. The prognosis is extremely grave. Most patients die of multiorgan failure within six to ten days. The presence of malignant disease is an absolute contraindication for liver transplantation. Diffuse liver infiltration from a urothelial cancer is extremely rare. There are only 5 cases from Europe in the medical literature. This appears to be the first reported case of ALF due to diffuse hepatic infiltration of metastatic transitional cell carcinoma in the US.