For patients with acute fulminant liver failure, imaging and histopathologic studies are indicated to reveal the underlying etiology, and metastatic small cell carcinoma should be included in the clinical differential diagnosis when appropriate.
Acute fulminant hepatic failure (FHF) is an uncommon but highly fatal condition that results from the massive destruction of liver tissue. Viral hepatitis and drug-induced liver damage predominate in North America and Europe, but the underlying precipitating factors differ around the world. 1 In children, indeterminate causes account for more than 50% of cases. 2 Other conditions associated with FHF are Budd-Chiari syndrome, vascular hypoperfusion, mushroom poisoning, Wilson disease, autoimmune hepatitis, and fatty liver of pregnancy. 3
Neoplastic lesions of the liver, mostly metastatic carcinomas, present with ductular obstruction with occasional mild elevations in aminotransferases. Rarely do space-occupying lesions lead to acute liver failure (ALF) with massive hepatocyte necrosis.
The authors report a case of rapidly progressing ALF due to metastatic small cell carcinoma to the liver. Small cell lung carcinoma (SCLC) is an aggressive tumor that often presents at an advanced stage. Although liver metastasis is common in this disease, development of FHF is extremely uncommon.
Case Presentation
A 90-year-old African American man presented to the emergency department (ED) of the Brooklyn Campus of the VA New York Harbor Health Care System (VANYHHS), with a persistent cough, worsening of shortness of breath, increasing right upper quadrant abdominal pain, and chronic constipation. He noted that he had smoked 1 pack per day for 40 years but quit 30 years ago. He had a medical history of chronic obstructive pulmonary disease (COPD), hypertension, prostate cancer treated 20 years earlier with external beam radiation therapy and with intramuscular leuprolide every 6 months for the previous 6.5 years, and gout. He was taking no hepatotoxic prescription medications and never used over-the-counter analgesics or abused alcohol. Five days before admission, he was treated for COPD exacerbation in the ED.
Blood chemistry at the time revealed significantly elevated liver function enzymes, including aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase (AST), and total bilirubin compared with baseline levels taken 3 months earlier (Table). Primary care follow-up was recommended. Physical examination on the day of admission was remarkable for normal blood pressure (137/74), emaciated appearance, and a large liver with right upper quadrant tenderness.
Repeat blood chemistries showed a further rise in liver function tests. Acetaminophen level was < 1.0 μg/mL (therapeutic range 10-20 μg/mL). Hepatitis A, B, and C serologic testing was negative. Serum creatinine was elevated at 1.7 mg/dL and steadily increased to 3.2 mg/dL at the end of the hospital course. A chest X-ray and a noncontrast computed tomography (CT) scan of the chest showed left upper lobe ill-defined infiltrates/opacities. Noncontrast abdominal and pelvic CT revealed hepatomegaly and ascites. Hepatic ultrasound showed that the liver was enlarged, diffusely heterogeneous, and nodular in appearance. The patient was admitted for evaluation.
On day 2 of admission, the patient reported “numbness of digits.” Serum glucose was measured and found to be low (36 mg/dL) (reference range: 70-110 mg/dL). He was subsequently managed for refractory hypoglycemia, which was presumed to be a result of liver disease. On day 3, he was transferred to the intensive care unit for close monitoring and management. On day 4, the patient was still experiencing episodes of hypoglycemia despite glucagon and dextrose administration. He developed altered mental status and metabolic acidosis and was intubated. Repeat laboratory tests showed a significant increase in AST and ALT with an AST:ALT ratio of about 4. Serum ammonia levels also were increased at 198.6 μg/dL (reference range: 17-80 μg/dL). The platelet count decreased to as low as 86 x 103/μL (reference range:150-450 x 103/μL). The prothrombin time (PT) increased continuously to as high as 21.4 sec (reference range: 9.6-12.4 sec) as did the activated partial thromboplastin time (aPTT) to 65.1 sec (reference range: 28-36.3 sec). Afterward, the patient developed multiple organ failure, including hemodynamic instability requiring fluid resuscitation. On day 5, the patient died.