What is the management of acute fulminant hepatic failure?

Management of Acute Fulminant Hepatic Failure

Patients with acute fulminant hepatic failure require immediate admission to an intensive care unit, early contact with a transplant center, and systematic administration of N-acetylcysteine regardless of suspected etiology. 1

Definition and Diagnosis

Acute liver failure (ALF) is defined as:

• Evidence of coagulation abnormality (typically INR ≥1.5)
• Any degree of mental alteration (encephalopathy)
• No preexisting cirrhosis
• Illness duration of ≤26 weeks 1

Initial Assessment

1. Immediate laboratory evaluation:

   • Prothrombin time/INR and factor V
   • Complete blood count
   • Comprehensive metabolic panel
   • Arterial blood gases with lactate level
   • Arterial ammonia level
   • Serum acetaminophen level
   • Serological markers for hepatitis viruses (IgM VHA, HBsAg, anti-HBc IgM)
   • Toxicology screen in urine (amphetamine, cocaine) 1

2. Imaging and cardiac assessment:

   • Hepatic Doppler ultrasound
   • Echocardiography to assess cardiac function 1

Management Algorithm

Step 1: Initial Stabilization and Monitoring

• Transfer to ICU immediately upon diagnosis 1
• Continuous monitoring of mental status for encephalopathy progression
• Maintain serum sodium between 140-145 mmol/L
• Monitor blood glucose at least every 2 hours
• Perform tracheal intubation and sedation for progressive hepatic encephalopathy (Glasgow <8) 1

Step 2: Specific Interventions

• Administer N-acetylcysteine to all patients regardless of etiology 1
• Initiate empirical broad-spectrum antibiotics for patients with worsening hepatic encephalopathy or signs of SIRS 1
• Consider acyclovir if herpes simplex virus hepatitis is suspected (e.g., if fever present) 1
• Contact transplant center early for evaluation 1

Step 3: Management of Complications

Neurological Complications

• Minimize sedation depth
• Avoid benzodiazepines and psychotropic drugs like metoclopramide 1
• Avoid treatments aimed at lowering ammonia levels (lactulose, rifaximin) 1

Cardiovascular Support

• Assess volume status and cardiac function
• Use crystalloid fluids for initial volume expansion
• Administer norepinephrine for refractory hypotension 1

Respiratory Support

• Implement standard lung-protective ventilation strategies 1

Renal Support

• Initiate renal replacement therapy according to standard indications
• Avoid nephrotoxic drugs, including NSAIDs 1

Coagulation Management

• Avoid routine correction of coagulation abnormalities
• Restrict clotting factor administration to active bleeding or invasive procedures 1

Gastrointestinal Support

• Provide stress ulcer prophylaxis 1

Step 4: Transplantation Evaluation

Expedited liver transplantation should be considered for:

• Herpes virus hepatitis
• Wilson disease
• Fulminant autoimmune hepatitis unresponsive to steroids
• Budd-Chiari syndrome 2

Prognostic Indicators for Poor Outcomes

• CLIF-C ACLF score >70 at admission or Day 3 (associated with ~90% 90-day mortality)
• Four or more organ failures at Days 3-7 after diagnosis (90% 28-day mortality, 100% 90-day mortality) 2

Special Considerations

Palliative Care

• Consider palliative care consultation for all patients with ALF, regardless of transplant listing status 2
• Consider withdrawal of intensive care support in non-transplant candidates with ≥4 organ failures after one week of adequate intensive treatment 2

Common Pitfalls to Avoid

1. Delayed recognition: All patients with moderate to severe acute hepatitis should have immediate PT/INR measurement and mental status evaluation 1
2. Inappropriate sedation: Avoid medications that may worsen encephalopathy 1
3. Delayed transplant referral: Early contact with transplant centers is essential, as patients with multiple organ failures may still achieve >80% 1-year survival with transplantation 2
4. Unnecessary coagulation correction: Restrict clotting factor administration to active bleeding or invasive procedures 1
5. Nephrotoxic medications: Avoid drugs that may worsen renal function 1

With proper intensive care management and timely consideration for liver transplantation, survival rates for acute fulminant hepatic failure have improved considerably in recent decades, now exceeding 60% overall 3.