What is the management approach for a patient with acute liver failure due to malignant infiltration?

Management of Acute Liver Failure from Malignant Infiltration

Acute liver failure from malignant infiltration is managed with cancer-directed chemotherapy when feasible, not liver transplantation, as transplantation is contraindicated in these patients. 1

Diagnostic Confirmation

Establish the diagnosis rapidly through imaging and liver biopsy, as this is critical to prevent inappropriate transplant listing and guide cancer-specific treatment. 1

• Suspect malignant infiltration in patients with: massive hepatomegaly, prior cancer history, abdominal pain (present in 74% of cases), or ascites 1, 2
• Obtain hepatic imaging (CT, MRI, or ultrasound) to evaluate for liver masses, though only 44% of patients show discrete masses on imaging 1, 2
• Perform liver biopsy (preferably transjugular approach given coagulopathy) to confirm diagnosis and identify the specific malignancy 1
• Common malignancies causing this presentation include: lymphoma/leukemia (33%), breast cancer (30%), small cell lung cancer, colon cancer (7%), melanoma, gastric cancer, and pancreatic cancer 1, 2

A critical pitfall: Imaging studies can be nondiagnostic in up to 40% of cases, as diffuse sinusoidal infiltration may not produce discrete masses—biopsy is mandatory to avoid missing the diagnosis. 3, 2

Cancer-Directed Treatment

Initiate chemotherapy appropriate for the underlying malignancy immediately upon diagnosis, as this represents the only potential life-saving intervention. 1

• Lymphoma and leukemia may respond to chemotherapy with potential for recovery of hepatic function 4, 5
• Solid tumors (breast, lung, colon, melanoma) have uniformly poor prognosis with mortality approaching 90-100% within 3 weeks despite treatment 3, 2
• 90% of patients with lymphoma/leukemia have no prior cancer history at presentation, compared to only 25% with breast cancer—maintain high index of suspicion even without known malignancy 2

Notable exception: Rare case reports document successful treatment of lymphoma-related ALF with complete recovery after chemotherapy, though this remains exceptional rather than typical. 4, 5

Supportive Intensive Care

Provide aggressive ICU-level supportive care while pursuing cancer diagnosis and treatment, though prognosis remains grave. 1

Hemodynamic Management

• Maintain mean arterial pressure ≥50-60 mm Hg through fluid resuscitation with crystalloids as first choice 1
• Administer norepinephrine for refractory hypotension unresponsive to fluids 1

Metabolic Support

• Monitor blood glucose at least every 2 hours and manage hypoglycemia with continuous glucose infusions 1
• Correct electrolyte abnormalities including phosphate, magnesium, and potassium 1
• Initiate enteral nutrition early with moderate protein intake (approximately 60 grams per day) 1

Renal Support

• Use continuous renal replacement therapy rather than intermittent hemodialysis if dialysis is needed, as 44% develop concurrent renal impairment 1, 3

Neurological Management

• Monitor encephalopathy frequently and maintain serum sodium 140-145 mmol/L 1, 6
• Intubate for airway protection if encephalopathy progresses to grade III-IV 1, 6
• Avoid benzodiazepines as they worsen encephalopathy; use propofol for sedation if needed 1, 7

Coagulation Management

• Reserve fresh frozen plasma for active bleeding or invasive procedures only, not prophylactic correction 7
• Administer vitamin K though response is typically limited 7

Transplantation Contraindication

Liver transplantation is absolutely contraindicated in malignant infiltration causing ALF—proper diagnosis prevents futile transplant listing. 1

• Exclude underlying malignancy before considering transplantation in any ALF case, particularly with Budd-Chiari syndrome where malignancy-associated hypercoagulability may be causative 1
• Transjugular liver biopsy should be performed when etiology remains unclear after initial evaluation to identify malignant infiltration and prevent inappropriate transplant consideration 1

Prognosis

The prognosis is uniformly poor with 89% mortality within 3 weeks of presentation, regardless of treatment. 2

• Median survival from admission is 7 days (range 4-14 days) 3
• Interval from jaundice to encephalopathy is typically rapid at 7-12 days (median 10 days) 3
• No improvement in outcomes has occurred over the past two decades despite advances in chemotherapy for metastatic disease 3
• Lymphoma/leukemia cases have slightly better prognosis than solid tumors, with rare reports of complete recovery after chemotherapy 4, 5

Key clinical pearl: The rapid progression (jaundice to death within 2-3 weeks), massive hepatomegaly, and marked elevation of AST (often >700 IU/L) with relatively lower ALT elevation should trigger immediate consideration of malignant infiltration. 3, 2