What is the significance of the Acute-on-Chronic Liver Failure (ACLF) score in assessing liver disease severity and guiding treatment?

ACLF Score: Clinical Significance and Application

The CLIF-C ACLF score should be used as the primary prognostic tool in patients with acute-on-chronic liver failure, as it provides superior mortality prediction compared to traditional scores (MELD, MELD-Na, Child-Pugh) and should be calculated sequentially at days 3-7 to guide critical decisions about intensive care, liver transplantation, and futility of ongoing treatment. 1

Superior Prognostic Accuracy

The CLIF-C ACLF score demonstrates significantly better discrimination for mortality prediction than conventional scoring systems:

• The C-indices for 28-day and 90-day mortality are 0.76 and 0.73 respectively, significantly outperforming MELD (0.69,0.66), MELD-Na (0.68,0.66), and Child-Pugh (0.67,0.66) scores (p <0.001 for all comparisons). 1

• This superior performance has been validated across multiple international cohorts, establishing it as the gold standard for ACLF prognostication. 1

• The score performs similarly to ICU-specific scores (APACHE, SOFA) but is simpler to calculate and specifically designed for liver failure patients. 1

Score Components and Calculation

The CLIF-C ACLF score integrates three key elements:

• CLIF-C Organ Failure (OF) score: Evaluates six organ systems (liver, kidney, brain, coagulation, circulation, lungs) with specific thresholds for each. 1, 2

• Age: Incorporated as an independent mortality predictor. 1, 3

• White blood cell count: Reflects systemic inflammation burden. 1, 3

The resulting score ranges from 0-100, with higher scores indicating worse prognosis. 1

Dynamic Sequential Assessment: The Critical Advantage

Sequential calculation at days 3-7 after diagnosis provides more accurate prognostication than a single baseline measurement and is essential for clinical decision-making. 1

• Patients with ACLF-3 (three or more organ failures) who show improvement by day 3 have 40% mortality versus 79% in those without improvement. 1

• The trajectory of the score (improving vs. worsening) is an independent predictor of mortality regardless of initial ACLF grade. 1

• This dynamic assessment identifies patients who may benefit from continued aggressive support versus those in whom treatment may be futile. 1

Clinical Applications and Treatment Guidance

Risk Stratification

The score enables categorization into ACLF grades with distinct mortality risks:

• ACLF Grade 1: Single organ failure with lower short-term mortality. 2, 4
• ACLF Grade 2: Two organ failures with intermediate mortality. 2, 4
• ACLF Grade 3: Three or more organ failures with 78% 28-day mortality. 2, 4

Critical Care Decisions

• Identifies patients requiring ICU admission, as ACLF carries at least 15% 28-day mortality. 2

• Guides liver transplantation evaluation: Patients with persistently high or rising scores despite treatment should be expedited for transplant assessment. 1

• Establishes futility thresholds: Specific CLIF-C ACLF score cut-offs for futility of ongoing intensive care have been proposed and require further validation. 1

Precipitant Identification

The comprehensive workup required for score calculation simultaneously identifies treatable precipitants:

• Bacterial infections, severe alcohol-related hepatitis, hepatitis B reactivation, GI hemorrhage with shock, and drug-induced organ injury. 1

Comparison with Alternative ACLF Scores

While multiple ACLF-specific scores exist, each has distinct characteristics:

• NACSELD ACLF score: Easy bedside tool but only captures advanced organ failure, potentially missing earlier ACLF stages. 1

• AARC score: Includes lactate, bilirubin, creatinine, INR, and hepatic encephalopathy; validated primarily in Asian populations. 1

• MELD-Lactate: Simpler model with excellent performance, particularly when lactate is added to CLIF-C ACLF, outperforming either score alone for 28-day, 90-day, and 1-year mortality. 1

Both EASL and AASLD guidelines recommend ACLF-specific scores (CLIF-C, NACSELD, or AARC) over conventional cirrhosis scores (MELD, MELD-Na) for critically ill patients with cirrhosis. 1

Important Caveats and Limitations

Subjectivity Issues

• Hepatic encephalopathy grading has inherent subjectivity. 1
• Timing of vasopressor initiation varies by clinician and institution. 1
• Reason for mechanical ventilation (airway protection vs. respiratory failure) may be unclear, particularly in retrospective assessments. 1

Static vs. Dynamic Nature

Most scores reflect clinical status at measurement time rather than true prognostic trajectory, emphasizing the importance of serial calculations. 1

Geographic Variations

Heterogeneous ACLF definitions across regions complicate score validation and comparison. 4

Practical Implementation Algorithm

1. At admission: Calculate baseline CLIF-C ACLF score using comprehensive workup (blood counts, biochemistry, INR, creatinine, bilirubin, clinical assessment of encephalopathy and circulatory status). 1

2. Days 3-7: Recalculate score to assess trajectory. 1

3. Interpret trajectory:

   • Improving score → Continue aggressive support
   • Stable or worsening score with ACLF-3 → Expedite transplant evaluation or discuss goals of care
   • Persistently high score (>64 proposed in some studies) → Consider futility discussions 1

4. Use in conjunction with precipitant treatment: The score guides prognosis while simultaneously treating reversible factors (infections, bleeding, hepatotoxins). 1