What are the EASL (European Association for the Study of the Liver) and APASL (Asian Pacific Association for the Study of the Liver) guidelines for managing Acute-on-Chronic Liver Failure (ACLF)?

EASL and APASL Guidelines for Acute-on-Chronic Liver Failure

Key Definitional Differences Between EASL and APASL

The EASL-CLIF definition applies to patients with cirrhosis (including those with previous decompensation) and defines ACLF based on organ failure assessment, while the APASL definition is restricted to patients with acute liver dysfunction triggered by acute intrahepatic precipitants and includes both cirrhotic patients without prior decompensation and those with non-cirrhotic chronic liver disease. 1

EASL-CLIF Definition Characteristics:

• Applies only to patients with established cirrhosis 1, 2
• Accepts both intrahepatic and extrahepatic precipitants (bacterial infection, gastrointestinal bleeding, surgery) 1
• Includes patients with previous decompensation episodes 2, 3
• Based on the CLIF-SOFA score evaluating six organ systems 4
• Identifies patients in intermediate and late disease stages 3

APASL Definition Characteristics:

• Restricted to acute intrahepatic precipitants only 1
• Does NOT consider bacterial infection, gastrointestinal bleeding, or surgery as precipitating events 1
• Applies to cirrhotic patients WITHOUT prior decompensation 1, 2
• Also includes patients with non-cirrhotic chronic liver disease 1, 2, 3
• Recognizes patients in earlier disease stages 3

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EASL Clinical Practice Guidelines (2023)

Recognition and Diagnosis

ACLF is characterized by functional failure of one or more of six major organ systems (liver, kidney, brain, coagulation, circulation, respiration) with 28-day mortality ≥20%. 1

Organ Failure Criteria (CLIF-SOFA):

• Liver failure: Bilirubin ≥12 mg/dL 4
• Kidney failure: Creatinine ≥2 mg/dL 4
• Cerebral failure: Hepatic encephalopathy grade III-IV 4
• Coagulation failure: INR ≥2.5 or platelet count ≤20,000/mm³ 4
• Circulatory failure: Use of vasopressors 4
• Respiratory failure: PaO₂/FiO₂ ≤200 or SpO₂/FiO₂ ≤214 4

ACLF Grading System:

• ACLF-1: Single kidney failure OR single non-kidney organ failure with creatinine 1.5-1.9 mg/dL and/or hepatic encephalopathy grade 1-2 4
• ACLF-2: Two organ failures 4
• ACLF-3: Three or more organ failures (28-day mortality ~78%) 4

Triage and ICU Admission

Patients with ACLF should be admitted to ICU within the first 6 hours after diagnosis. 1

Indications for ICU Admission:

• Variceal bleeding requiring intervention 1
• Grade III-IV hepatic encephalopathy requiring airway protection 1
• Septic shock 1

Contraindications to ICU Admission:

• Comorbidities with very poor prognosis 1
• Severe pulmonary (GOLD 3-4), cardiac (NYHA III-IV), or neurological disease with ACLF-3 1
• Advanced neoplasm with life expectancy <6 months 1
• Severe frailty with Karnofsky performance status ≤40 1

Management Principles

Early identification and treatment of precipitating factors is crucial, with aggressive multidisciplinary organ support to bridge patients to potential liver transplantation or recovery. 1, 4

Treatment of Precipitants:

• Proven microbial infection with sepsis 1
• Severe alcohol-related hepatitis 1
• Drug toxicity 4
• Viral hepatitis reactivation 4
• Gastrointestinal bleeding 1

Prognostic Assessment:

• Risk of death should be evaluated 3-7 days after starting full organ support, not at admission 1
• CLIF-C ACLF score incorporates organ failure score, age, and white blood cell count 4
• Provides better prognostic accuracy than MELD or MELD-Na 4

Futility Criteria

The presence of 4 or more organ failures or CLIF-C ACLF score >70 points at 3-7 days after ICU admission should lead to re-evaluation of maintaining organ support in the absence of liver transplant options. 1

• Patients with ACLF-3 and CLIF-C ACLF score ≥70 at 48 hours have 100% 28-day mortality 1
• Patients with four or more organ failures at Days 3-7 have 90-100% mortality 1

Specific Management Considerations

Autoimmune Hepatitis-ACLF:

• Histological assessment warranted to verify active inflammation 1
• Transjugular liver biopsy recommended with severe coagulopathy 1
• Corticosteroid therapy effective in patients without baseline sepsis (75% vs 48% 90-day survival) 1
• 66% of patients ineligible for corticosteroids due to active sepsis or contraindications 1

Respiratory Support:

• Lung protective ventilation with tidal volume 6 mL/kg predicted body weight 1
• Low plateau pressure <30 cm H₂O 1
• Low PEEP strategy (<10 cm H₂O) for mild ARDS to minimize impaired venous return 1
• High PEEP may be required for moderate-severe ARDS (PaO₂/FiO₂ <200) 1

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Clinical Implications of Definitional Differences

Practical Impact on Patient Management:

The choice between EASL and APASL definitions affects which patients are diagnosed with ACLF and subsequently receive intensive care and transplant evaluation. 1, 2, 3

EASL Definition Captures:

• Broader patient population including those with extrahepatic precipitants 1
• Patients with previous decompensation episodes 2
• More advanced disease stages 3

APASL Definition Captures:

• Earlier disease stages 3
• Patients without established cirrhosis 2, 3
• Only intrahepatic precipitant-driven cases 1

Common Pitfalls:

• Do not apply APASL criteria to patients with bacterial infection as the precipitant - this is excluded from their definition 1
• Document presence or absence of cirrhosis - affects transplant evaluation and prognosis 2
• Non-cirrhotic ACLF may have different organ failure patterns - recognize this when using APASL criteria 2
• Avoid delaying ICU admission - EASL recommends admission within 6 hours of diagnosis 1

Prognostic Scoring Systems:

The CLIF-C ACLF score (EASL-based) provides superior prognostic accuracy compared to traditional scores and should guide management decisions. 4

• MELD-Lactate model outperforms MELD, MELD-Na, or lactate alone 4
• AARC score (used with APASL definition) includes lactate, bilirubin, creatinine, INR, and hepatic encephalopathy 4
• Serial assessment more valuable than single time-point evaluation 1

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Palliative Care Integration

All patients with cirrhosis admitted to ICU or diagnosed with ACLF should receive palliative care consultation to define prognosis, determine goals of care, and document advance directives, irrespective of transplant listing status. 1

Key Palliative Care Metrics:

• Surrogate decision-maker identified within 48 hours of admission 1
• Goals of care discussion before hemodialysis or mechanical ventilation >48 hours 1
• Palliative care or hospice offered to non-transplant candidates with treatment-refractory complications 1