Case Presentation: A 95 year old woman with a remote history of treated breast cancer and endometrial cancer presented to the hospital with severe abdominal pain and somnolence.
One month prior, the patient was living independently in her usual state of health. She developed dysuria and malaise and visited an outside hospital. Routine laboratory testing showed AST 94 U/L, ALT 40 U/L, alkaline phosphatase 269 U/L, total bilirubin 3.0 mg/dL, and INR 1.4. CT abdomen/pelvis showed many hepatic lesions suspected to be metastases. Tumor markers showed CA-125 1072 U/mL, CEA 38.1 ng/mL, and CA 19-9 293,725 U/mL. Urinalysis was consistent with a urinary tract infection, for which she was treated. In follow-up with her primary care physician, she chose to forgo any further evaluation or treatment for underlying malignancy and, instead, opted to pursue hospice care.

Shortly after, the patient developed mild abdominal pain that worsened quickly, requiring escalating doses of narcotics. She became increasingly confused and somnolent. Given ongoing pain, the patient’s family brought her into the Emergency Department. The patient’s family requested medical evaluation of reversible causes, given the patient’s rapid decline in health. Laboratory testing revealed pH 6.9, bicarbonate 5 mmol/L, lactate 19 mmol/L, and potassium of 8.1 mmol/L. Liver function testing showed AST 2400 U/L, ALT 558 U/L, alkaline phosphatase 445 U/L, total bilirubin 5.3 mg/dL, and INR 2.5. Upon further discussion with the patient’s family, treatment focused on comfort was pursued, and the patient expired shortly after. Autopsy revealed innumerable tumor nodules encompassing a quarter of the total liver volume and extensive necrosis of most of the remaining liver parenchyma. Pathology showed carcinoma of unknown primary, not consistent with endometrial, breast, or neuroendocrine origin.

Discussion: Acute liver failure (ALF) causes sudden hepatic dysfunction, coagulopathy, and encephalopathy, with hyperacute liver failure occurring when the time between the onset of jaundice and the development of encephalopathy is less than 7 days. Though the liver is a common site of metastatic carcinoma, ALF is rarely caused by metastatic carcinoma (<1% of cases); most malignant causes of ALF are due to infiltration from hematologic malignancy. ALF due to metastatic carcinoma may be difficult to diagnose, and ALF can be the presenting sign of malignancy. Laboratory abnormalities are similar to other causes of ALF, and imaging may be nondiagnostic; biopsy is often needed to make the diagnosis.

Mortality is very high (>90%). Most patients deteriorate precipitously and die from ALF rather than underlying malignancy. Malignancy is a contraindication to liver transplantation and liver dysfunction may preclude chemotherapy, though infiltrative hematologic malignancy may respond to treatment. Early recognition and oncology consultation is necessary to begin treatment as expediently as possible. For patients unlikely to respond to treatment, prognosis and goals of care should be discussed.

Conclusions: Hospitalists commonly encounter patients with ALF and patients suffering from complications of metastatic malignancy. Hospitalists should understand that metastatic carcinoma is a rare but nearly universally fatal cause of ALF and should prompt a discussion of prognosis and goals of care.