What is the management of Acute-on-Chronic Liver Failure (ACLF)?

Management of Acute-on-Chronic Liver Failure (ACLF)

ACLF requires prompt recognition, intensive care support, treatment of precipitating factors, and early evaluation for liver transplantation as the definitive management strategy for eligible patients.

Definition and Diagnosis

ACLF is characterized by:

• Acute onset with rapid clinical deterioration
• Liver failure (elevated bilirubin and INR) in patients with chronic liver disease
• Presence of at least one extrahepatic organ failure (neurologic, circulatory, respiratory, or renal)
• High short-term mortality (20-40% at 28 days) 1

Diagnostic Criteria

Several classification systems exist:

• EASL-CLIF criteria: Grades ACLF from 1-3 based on number of organ failures 1
• NACSELD criteria: Focuses on patients with ≥2 extrahepatic organ failures 1
• APASL criteria: Emphasizes acute hepatic insult in chronic liver disease 1

Initial Management

Triage and Monitoring

• Admit to ICU or intermediate care setting for patients with ACLF 1
• Monitor organ function (liver, kidney, brain, lung, coagulation, circulation) frequently 1
• Implement continuous pulse oximetry monitoring 1, 2

Identification and Treatment of Precipitating Factors

• Early identification is critical for management of:

  • Bacterial infections (most common precipitant)
  • Alcoholic hepatitis
  • Gastrointestinal bleeding
  • Viral hepatitis reactivation (especially HBV) 1

• Specific treatments:

  • For HBV reactivation: Initiate nucleoside analogues (tenofovir, entecavir) immediately 1
  • For bacterial infections: Early broad-spectrum antibiotics within 1 hour of shock onset 1

Organ-Specific Support

Circulatory Support

• Volume expansion with crystalloids as first-line treatment 3
• For refractory hypotension: Norepinephrine is the vasopressor of choice 3
• Avoid terlipressin in patients with ACLF Grade 3 due to increased risk of respiratory failure 2

Respiratory Support

• Assess oxygenation before initiating any therapy 2
• Discontinue treatments if SpO2 decreases below 90% 2
• Patients with volume overload are at increased risk of respiratory failure 2
• Consider tracheal intubation when Glasgow score <8 3

Neurological Support (Hepatic Encephalopathy)

• For overt hepatic encephalopathy:
  • Use nonabsorbable disaccharides (lactulose) 1
  • Consider oral rifaximin as adjunctive therapy 1
  • Enteral polyethylene glycol is an alternative to lactulose 1
  • L-ornithine L-aspartate (LOLA) may be beneficial 1
  • Avoid benzodiazepines 3

Renal Support

• For hepatorenal syndrome:
  • Combination of albumin and terlipressin (with caution in ACLF-3) 4
  • Continuous renal replacement therapy for severe acute kidney injury 4

Coagulation Management

• Guided by thromboelastography rather than conventional tests 4
• Administer vitamin K for coagulopathy 3
• Use fresh frozen plasma only for active bleeding or before invasive procedures 3
• Transfuse platelets for counts <10,000/mm³ or before procedures 3

Gastrointestinal Support

• For portal hypertensive bleeding:

  • Octreotide or somatostatin analogs 1
  • Proton pump inhibitors 1
  • Antibiotic prophylaxis 1
  • Consider transjugular intrahepatic portosystemic shunt (TIPS) for recurrent variceal bleeding after failed medical/endoscopic therapy 1

• For ascites:

  • Large volume paracentesis (LVP) with albumin for tense ascites causing hemodynamic, renal, or respiratory compromise 1
  • Avoid LVP in patients with spontaneous bacterial peritonitis (SBP) 1

Advanced Therapeutic Options

Liver Transplantation

• Early referral to transplant centers is critical 1
• Even patients with multiple organ failures may achieve >80% 1-year survival with transplantation 4
• Transplantation is the only definitive treatment for eligible patients 3

Extracorporeal Liver Support

• Current evidence does not support routine use of albumin dialysis (MARS) or fractionated plasma separation and adsorption (Prometheus) 1
• May be considered in selected cases, especially those with MELD >30 1

Prognostication and Futility

• Consider withdrawal of intensive care support in patients who:

  • Are not transplant candidates
  • Have ≥4 organ failures after one week of adequate intensive treatment 1
  • Show 90-100% mortality at 28-90 days 3

• Palliative care consultation should be obtained for all patients with cirrhosis admitted to ICU or diagnosed with ACLF, regardless of transplant listing status 3

Common Pitfalls and Caveats

1. Delayed recognition of ACLF leads to worse outcomes - monitor patients with decompensated cirrhosis closely for signs of organ failure

2. Respiratory complications are common and potentially fatal - maintain continuous pulse oximetry and avoid terlipressin in patients with hypoxia or ACLF Grade 3

3. Infection surveillance is critical - patients with ACLF have increased susceptibility to infections and sepsis

4. Transplant eligibility may be compromised by certain treatments - consider this when managing patients who may be transplant candidates

5. Futile care should be avoided - establish goals of care early and reassess frequently based on clinical response and organ failure progression