In a patient with known cirrhosis who has developed acute‑on‑chronic liver failure with multi‑organ failure, should we refer for urgent liver transplantation and what are the eligibility criteria?

Urgent Liver Transplantation Referral for ACLF with Multi-Organ Failure

Yes, refer immediately for urgent liver transplantation evaluation—liver transplantation is the definitive treatment for ACLF with multi-organ failure, and early referral is critical because the "transplantation window" is often narrow in these patients. 1

Immediate Referral Criteria

All patients with ACLF Grade 2-3 require immediate transplant center referral without delay. 2 The grading system determines urgency:

• ACLF Grade 1: Single kidney failure OR single cerebral failure with creatinine 132-170 mmol/L OR single organ failure (liver/coagulation/circulation/respiration) with creatinine 132-170 mmol/L and/or hepatic encephalopathy 1
• ACLF Grade 2: Two organ failures 1
• ACLF Grade 3: Three or more organ failures 1

Patients with cirrhosis who survive ICU discharge have <25% one-year survival without transplantation and should be referred systematically to a liver transplant unit. 1

Eligibility Assessment Framework

Favorable Transplant Candidacy Indicators

Improvement or stabilization of organ failures within 3-7 days, especially pulmonary and circulatory, is a prerequisite for acceptable transplant outcomes. 1 Reassess ACLF grade at 3-7 days to predict outcome—improving organ function indicates potential for recovery and transplant candidacy. 2

Key favorable factors include:

• Stabilization or improvement in CLIF-C ACLF score over 48-72 hours 1
• Improvement in MELD score with treatment 1
• Fewer than 4 organ failures 1
• CLIF-C ACLF score <70 points 1
• Absence of severe cardiopulmonary disease 1
• Respiratory failure with PaO2/FiO2 ratio that has not progressed to prohibitive levels 1

Contraindications and Poor Prognostic Indicators

Absolute contraindications requiring palliative care discussion:

• ≥4 organ failures at Days 3-7 after ACLF-3 diagnosis (90-100% mortality at 28-90 days) 1
• CLIF-C ACLF score >70 points at admission or Day 3 (~90% 90-day mortality) 1
• CLIF-C ACLF score ≥70 at 48 hours after ICU admission (100% 28-day mortality) 1
• CLIF-C ACLF score >64 in patients with ACLF-3 (100% mortality) 1

Relative contraindications requiring case-by-case evaluation:

• Major cardiopulmonary disease 1
• Severe progressive hypoxemia 1
• Active untreated bacterial infection (potentially reversible) 1
• Active alcohol use (potentially reversible) 1
• Severe comorbidities 1

Critical Management Pitfalls to Avoid

Common errors that worsen transplant candidacy:

• Delaying transplant center referral—late referral may make transplantation impossible due to rapid ACLF evolution 1
• Delaying antibiotics when infection is suspected—empirical broad-spectrum antibiotics are mandatory and should not be delayed while awaiting cultures 2
• Giving prophylactic blood products—this obscures disease progression monitoring 2
• Excessive crystalloid administration—avoid volume overload while maintaining hemodynamics 2
• Failing to identify and treat precipitating factors (infection, GI bleeding, viral reactivation, alcohol-related hepatitis, drug-induced liver injury) 1, 2

Bridge Therapy Considerations

While awaiting transplant evaluation and listing:

• Artificial liver support systems (MARS, Prometheus) may provide short-term survival improvement (14-28 days) in ACLF with multiple organ failure, potentially allowing access to transplantation 1
• These systems show significant improvement in hepatic encephalopathy and hepatorenal syndrome but do not improve overall survival 1, 3
• Renal replacement therapy is recommended for patients with hepatorenal syndrome-AKI who have failed pharmacotherapy and are listed or being considered for transplantation 1

Post-Transplant Outcomes

In carefully selected patients, 1-year survival after transplant for ACLF is 78% compared to <10% without transplant. 2 However, outcomes are heterogeneous:

• Some studies show similar survival between ACLF and non-ACLF transplant recipients 1
• Meta-analyses show lower post-transplant survival in ACLF (1-year: 86.0% vs 91.9%; 5-year: 66.9% vs 80.7%) with increased resource utilization 1
• Higher rates of complications, longer ICU/hospital stays, and increased infection risk post-transplant 1

Futility Assessment

Prognosis should be determined after 3-7 days of full organ support before declaring futility. 1 In patients with no transplant option, withdrawal of organ support and palliative care should be considered when ≥4 organ failures or CLIF-C ACLF score >70 persists after 3-7 days of full support. 1