What is the management of acute on chronic liver failure?

Management of Acute-on-Chronic Liver Failure

Patients with acute-on-chronic liver failure (ACLF) require immediate ICU-level supportive care focused on organ system support, identification and treatment of precipitants (particularly infections and alcohol-related hepatitis), and urgent evaluation for liver transplantation, as ACLF carries a 28-day mortality of 20% or more. 1

Recognition and Initial Assessment

ACLF is defined as a severe form of acutely decompensated cirrhosis characterized by functional failure of one or more of six major organ systems (liver, kidney, brain, coagulation, circulation, and respiration) with systemic inflammation. 1 This differs fundamentally from acute liver failure, which occurs in patients without pre-existing cirrhosis. 1

Key diagnostic features include:

• Acute decompensation (ascites, encephalopathy, gastrointestinal hemorrhage) in a patient with known cirrhosis 1
• Organ system failure(s) using standardized criteria 1
• 28-day mortality ≥20% (versus ≤5% in decompensated cirrhosis without ACLF) 1

Triage and ICU Admission

All patients with ACLF should be considered for ICU admission given the high mortality and need for organ support. 1 The decision for ICU transfer should be made early when organ failures develop, as delayed recognition worsens outcomes. 1

Identification and Management of Precipitants

Infection Management

Infection is one of the most critical precipitants of ACLF and requires immediate diagnosis and treatment. 1 Given the high incidence and mortality of infection in ACLF, early empiric antibiotic therapy should be initiated while awaiting culture results. 1

• Obtain blood cultures, urine cultures, and diagnostic paracentesis if ascites is present 1
• Start broad-spectrum antibiotics immediately for suspected infection 1
• Avoid nephrotoxic agents when possible 2

Alcohol-Related Hepatitis

Severe alcohol-related hepatitis is a recognized precipitant that should be identified through detailed history. 1 Treatment of the underlying alcohol-related liver injury may be considered as part of precipitant management. 1

Gastrointestinal Bleeding

Active bleeding should be controlled promptly as it can trigger the inflammatory cascade leading to organ failures. 3, 4

Organ System Support

Hemodynamic Support

Maintain mean arterial pressure of 50-60 mm Hg through careful fluid management and vasopressor support. 2

• Use crystalloid fluids as first-line for volume expansion 5
• Monitor volume status carefully; consider pulmonary artery catheterization in hemodynamically unstable patients 2
• If fluid replacement fails to maintain adequate blood pressure, use norepinephrine as the preferred vasopressor 5
• Avoid vasopressin 2

Renal Support

For acute kidney injury requiring dialysis, use continuous renal replacement therapy rather than intermittent hemodialysis. 2

• Avoid nephrotoxic agents 2
• Monitor and supplement electrolytes (phosphate, magnesium, potassium) 2

Hepatic Encephalopathy Management

Monitor mental status frequently and escalate care as encephalopathy progresses. 2

• Position patient with head elevated at 30 degrees 2
• For grades III-IV encephalopathy, perform endotracheal intubation for airway protection 2
• Control seizures with phenytoin; avoid benzodiazepines when possible 2
• Consider lactulose administration to reduce ammonia levels, though evidence for improved outcomes is limited 2
• Maintain serum sodium between 140-145 mmol/L to prevent cerebral edema 5

Coagulation Management

Reserve fresh frozen plasma (FFP) for active bleeding or invasive procedures, not for prophylactic correction of INR. 2

• Administer vitamin K 2
• Give platelets for counts <10,000/mm³ or before invasive procedures 2
• Consider recombinant activated factor VII for invasive procedures 2
• Use thromboelastography to guide evaluation of coagulation pathways and hyperfibrinolysis; prophylactic blood product transfusions are not recommended 6

Respiratory Support

Provide mechanical ventilation as needed for respiratory failure, which is one of the six organ systems that can fail in ACLF. 1

Metabolic Management

Initiate early enteral nutrition with moderate protein intake (approximately 60 grams per day). 2

• Manage hypoglycemia with continuous glucose infusions 2
• If enteral feeding is contraindicated, use parenteral nutrition despite increased risk of fungal infection 2

Infection Prevention

Implement prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors. 2 However, balance this against the potential for increased infection risk with acid suppression. 1

Liver Transplantation

Liver transplantation is increasingly recognized as an effective rescue therapy for ACLF, with post-transplant survival rates of 80-90% even in patients with 3 or more organ failures. 1, 6

Transplant Evaluation

• Contact transplant center early for all patients with ACLF 1
• Even patients with multiple organ failures may achieve excellent post-transplant outcomes 6
• Disease-directed care including transplant evaluation does not preclude palliative care consultation 1

Bridging Therapies

While awaiting transplantation, consider:

• Extracorporeal liver support systems (though evidence of efficacy remains uncertain) 2, 6
• Continuous renal replacement therapy for renal support 2
• Full ICU-level organ support 1

Palliative Care Integration

A palliative care consultation should be considered for all patients with ACLF to define prognosis and determine goals of care. 1

• Palliative care and transplant listing are not mutually exclusive 1
• Engage palliative care early, ideally at ACLF diagnosis or ICU admission 1
• Any care team member can provide primary palliative care including advanced care planning 1

Common Pitfalls

Avoid these critical errors:

• Delaying ICU transfer until multiple organ failures have developed 1
• Failing to identify and treat infections early 1
• Using intermittent hemodialysis instead of continuous renal replacement therapy 2
• Prophylactic correction of coagulopathy with FFP (increases volume overload without proven benefit) 2, 6
• Dismissing patients as "too sick" for transplant evaluation without formal assessment 1, 6
• Delaying palliative care consultation until after delisting decisions are made 1

Investigational Therapies

While not yet standard of care, emerging therapies under investigation include: 6, 7

• Hepatocyte stem cell therapies 6
• Advanced extracorporeal liver support devices 6
• Immunomodulatory therapies targeting the excessive systemic inflammation characteristic of ACLF 3, 7

The pathophysiology of ACLF involves intense systemic inflammation driven by pathogen-associated and damage-associated molecular patterns, leading to organ failures through tissue hypoperfusion, immune-mediated damage, and mitochondrial dysfunction. 3 Future therapies targeting these mechanisms are urgently needed. 1, 7