Critical care hepatology: A narrative review of current concepts and management

Table 3 Prognostic models and futility assessment in acute-on-chronic liver failure

Score	Components	Outcome predicted	Use/threshold	Type
Established prognostic and futility scores in the critical illness setting
CLIF-C ACLF[102,103]	CLIF-C OF + age + WBC	28- and 90-day mortality in ACLF patients	Score ≥ 64 → 28-day mortality ~80%; used to assess LT candidacy futility	Prognostic + futility
CLIF-C OF[10,102]	Liver (bilirubin), kidney (creatinine), brain (HE grade), coagulation (INR), circulation (MAP), lungs (PaO2/FiO2)	OF burden and short-term mortality	Defines ACLF grade (1-3) per EASL-CLIF criteria; grade 3 = ~75% 28-day mortality	Prognostic
MELD/MELD-Na[104,105]	Creatinine, bilirubin, INR (+ sodium for MELD-Na)	90-day mortality; waitlist priority	MELD > 35 in ACLF associated with futile outcomes without LT	Prognostic + futility
NASCELD-ACLF[15,106]	Number of extrahepatic OFs (kidney, brain, circulation, lungs)	30-day in-hospital mortality in cirrhotic inpatients	≥ 2 OFs = ACLF; 30-day mortality ~50%; ≥ 3 OFs approaches futility (~75%)	Prognostic + futility
APACHE II/III	Age, vitals, GCS, AaDO2, pH, electrolytes, creatinine, Hct, WBC	ICU mortality (general critical care score applied to ACLF)	APACHE II > 20 in liver patients correlates with high ICU mortality; used adjunctively	Prognostic
APACHE IV[107]	Acute physiology variables, age, chronic health status, admission diagnosis	ICU and hospital mortality in critically ill patients, including cirrhosis cohorts	Used as a general ICU severity score; in a cohort of 64 critically ill patients with cirrhosis, median APACHE IV scores were significantly higher among ICU non-survivors (117 vs 79.5) and demonstrated good discrimination for ICU mortality (AUC = 0.87)	Prognostic
SOFA[10,108]	PaO2/FiO2, platelets, bilirubin, MAP/vasopressors, GCS, creatinine	Daily organ dysfunction course in ICU	Rising SOFA score (≥ 2-point increase) denotes clinical deterioration; high scores used in futility discussions	Prognostic + futility
Child-Pugh[108]	Bilirubin, albumin, PT, ascites, encephalopathy	Cirrhosis severity and surgical risk	Child C (10-15) in ACLF context predicts poor short-term prognosis; limited discrimination vs MELD	Prognostic
AARC-ACLF	Bilirubin, lactate, creatinine, PT-INR, HE grade	28-day mortality (Asia-Pacific cohorts)	AARC score 5-6 = 28-day mortality ~47%; ≥ 9 = ~100% (futility threshold used in India/APASL populations)	Prognostic + futility
LT-specific futility and post-transplant mortality scores
TAM score[86]	4 pre-LT binary criteria (1 point each): Age ≥ 53 years, arterial lactate ≥ 4 mmol/L, mechanical ventilation with PaO2/FiO2 ≤ 200 mmHg, WBC ≤ 10 G/L	1-year post-LT mortality in ACLF grade 3 patients (multicenter European cohort, n = 152)	TAM > 2 → 1-year post-LT survival 83% (futility); TAM ≤ 2 → survival 83%. Assessed immediately before LT. Validated in independent multicenter cohort	Futility/LT
CLIF-C ACLF > 64[103]	CLIF-C OF score + age + WBC (same formula as CLIF-C ACLF; threshold specific to LT futility context)	Post-LT mortality and ICU futility in ACLF-3; validated at Royal Free Hospital (n = 202)	Score > 64 at 48 hours ICU → high 28-day mortality (~80%); used as a threshold for LT futility discussions alongside TAM; EASL CPG 2023 cites ≥ 70 for ICU withdrawal in non-LT candidates	Futility/LT
≥ 3 OFs[22]	ACLF grade 3 as defined by CLIF-C OF criteria: Hepatic, renal, brain, coagulation, circulatory, and/or respiratory failure (any ≥ 3 simultaneously)	28-day mortality; probability of benefit from LT	ACLF-3 → 28-day mortality ~75%-79% without LT; > 3 OFs (i.e., 4-6) associated with increasing futility risk; EASL CPG cites ≥ 4 OFs + CLIF-C ACLF > 70 for ICU withdrawal	Futility/LT
Futility consensus framework[83]	Consensus framework by 35 international experts (Delphi method): Severe frailty, persistent fever or < 72 hours appropriate antimicrobials for ongoing sepsis, uncontrolled septic shock, and other contraindications; not a single numeric score but a structured decision framework	Definition of futile LT and criteria to delay or deny LT in critically ill cirrhotic/ACLF patients	Severe frailty OR active uncontrolled sepsis (< 72 hours antibiotics) = defer LT. Framework uses 1-year and 5-year post-LT survival benchmarks to define futility (< 50% at 5 year); meant to complement numeric scores with clinical judgment	Futility/LT
CFS ≥ 7[83,87]	9-point ordinal scale assessing activity, energy, function, and dependence: 1 (very fit) → 9 (terminally ill). Scores ≥ 7 = severely frail/completely dependent	Post-LT mortality; identifies patients too frail to survive transplantation regardless of hepatic disease severity	CFS ≥ 7 → independent predictor of post-LT mortality; endorsed by Weiss 2021 consensus as a criterion to defer or deny LT. Stabilization before LT (Huebener et al[87], 2018) with organ recovery associates with better post-LT survival	Futility/LT
SALT-M score > 2023[85]	Age, BMI, diabetes (pre-LT comorbidity); respiratory failure (PaO2/FiO2 < 200 or mechanical ventilation); circulatory failure (vasopressors); infection history; RRT use; WBC at LT - derived in 521 United States + 120 French ACLF-2/3 patients (MODEL Consortium)	1-year post-LT mortality in ACLF grade 2 or 3; c-statistic 0.72 (derivation) and 0.80 (external validation)	SALT-M > 30 → substantially elevated 1-year post-LT mortality risk (futility threshold cited in subsequent literature); outperforms MELD-Na, CLIF-C ACLF and BAR score for post-LT mortality prediction. Also estimates post-LT ICU length of stay (ACLF-LT-LoS sub-score)	Futility/LT
HALT (Zhuang)	Recipient age, number of organ failures, lactate, DCD graft, cold ischemia time	1-year post-LT mortality in HBV ACLF	Estimated mortality 66%-86% in highest-risk graft-recipient combination; proposed to identify futile transplantation	Futility/LT

This table summarizes established prognostic models and futility criteria used in critically ill patients with acute and chronic liver disease, including both general intensive care unit scores and liver-specific tools. It highlights their key components, predicted outcomes, and clinically relevant thresholds to support risk stratification, transplant decision-making, and identification of patients unlikely to benefit from continued intensive care or liver transplantation. CLIF-C ACLF: Chronic Liver Failure Consortium acute-on-chronic liver failure score; CLIF-C OF: Chronic Liver Failure Consortium organ failure score; WBC: White blood cell count; ACLF: Acute-on-chronic liver failure; LT: Liver transplantation; HE: Hepatic encephalopathy; INR: International normalized ratio; MAP: Mean arterial pressure; OF: Organ failure; EASL-CLIF: European Association for the Study of the Liver-Chronic Liver Failure; MELD: Model for end-stage liver disease; MELD-Na: Model for end-stage liver disease including sodium; NASCELD: North American Consortium for the Study of End-Stage Liver Disease; APACHE: Acute Physiology and Chronic Health Evaluation; GCS: Glasgow Coma Scale; Hct: Hematocrit; ICU: Intensive care unit; AUC: Area under the curve; SOFA: Sequential Organ Failure Assessment; PaO₂/FiO₂: Ratio of arterial oxygen partial pressure to fraction of inspired oxygen; PT: Prothrombin time; AARC: Asian Pacific Association for the Study of the Liver Acute-on-Chronic Liver Failure Research Consortium; APASL: Asian Pacific Association for the Study of the Liver; TAM: Transplantation for acute-on-chronic liver failure-3 model; CPG: Clinical practice guidelines; EASL: European Association for the Study of the Liver; CFS: Clinical Frailty Scale; SALT-M: Survival After Liver Transplantation in acute-on-chronic liver failure model; BMI: Body mass index; BAR: Balance of Risk score; RRT: Renal replacement therapy; LoS: Length of stay; DCD: Donation after circulatory death; HBV: Hepatitis B virus.