What is the best approach to assess and manage an adult patient with a history of chronic liver disease, such as cirrhosis or hepatitis, presenting with acute deterioration in liver function and potential Acute-on-Chronic Liver Failure (ACLF)?

ACLF Scoring and Assessment

Diagnostic Criteria and Grading System

The diagnosis and grading of ACLF should be based on the CLIF-C Organ Failure (CLIF-OF) score, which evaluates six organ systems and defines organ failures with specific thresholds that predict high short-term mortality. 1

Organ Failure Definitions

The CLIF-OF score defines organ failures using the following criteria 1, 2:

• Liver failure: Bilirubin ≥12 mg/dL
• Kidney failure: Creatinine ≥2 mg/dL
• Cerebral failure: Hepatic encephalopathy grade III-IV (West Haven criteria)
• Coagulation failure: INR ≥2.5 or platelet count ≤20,000/mm³
• Circulatory failure: Mean arterial pressure <70 mmHg or use of vasopressors (dopamine >5 μg/kg/min, epinephrine >0.1 μg/kg/min, or any dose of norepinephrine)
• Respiratory failure: PaO₂/FiO₂ ≤200 or SpO₂/FiO₂ ≤214

ACLF Grading Classification

ACLF is classified into distinct grades based on the number and type of organ failures 1, 2:

• No ACLF: No organ failure, OR single non-kidney organ failure with creatinine <1.5 mg/dL and no hepatic encephalopathy
• ACLF Grade 1a: Single kidney failure only
• ACLF Grade 1b: Single non-kidney organ failure with creatinine 1.5-1.9 mg/dL and/or hepatic encephalopathy grade 1-2
• ACLF Grade 2: Two organ failures
• ACLF Grade 3: Three or more organ failures

The 28-day mortality increases dramatically with grade: ACLF-1 has approximately 23% mortality, ACLF-2 has approximately 32% mortality, and ACLF-3 has approximately 74-78% mortality 2, 3.

Prognostic Scoring Systems

CLIF-C ACLF Score (Primary Recommendation)

The CLIF-C ACLF score provides superior prognostic accuracy compared to MELD or MELD-Na and should be used for risk stratification in ACLF patients. 1, 2

The CLIF-C ACLF score is calculated as 1:

10 × [0.033 × CLIF-OF score + 0.04 × Age (years) + 0.63 × Ln(WBC count)]

This score incorporates organ failures, age, and white blood cell count, capturing both the severity of organ dysfunction and systemic inflammation 1, 2. It can be calculated serially at admission and up to Day 7 to assess disease trajectory 1.

Alternative Scoring Systems

While the CLIF-C ACLF score is preferred, other validated systems include 1, 2:

• NACSELD ACLF score: Includes advanced extrahepatic organ failure, age, MELD, WBC count, and serum albumin measured at hospital admission
• AARC score: Includes serum bilirubin, creatinine, lactate, INR, and hepatic encephalopathy evaluated at hospital/ICU admission

All ACLF-specific scores demonstrate better diagnostic performance than MELD, MELD-Na, or ICU-specific scores (APACHE II, SOFA) for predicting mortality in ACLF. 1

Clinical Assessment Algorithm

Step 1: Identify Acute Decompensation

Look for acute development or worsening of 1:

• Ascites
• Overt hepatic encephalopathy
• Gastrointestinal hemorrhage
• Non-obstructive jaundice
• Bacterial infections

Step 2: Assess Organ Function

Systematically evaluate all six organ systems using the CLIF-OF criteria detailed above 1, 2. Obtain:

• Bilirubin, INR, platelet count
• Creatinine
• Hepatic encephalopathy grade (West Haven criteria)
• Mean arterial pressure and vasopressor requirements
• Arterial blood gas with PaO₂/FiO₂ ratio or SpO₂/FiO₂ ratio

Step 3: Grade ACLF Severity

Apply the grading system based on number and type of organ failures 1, 2.

Step 4: Calculate CLIF-C ACLF Score

Use the formula above with age, WBC count, and CLIF-OF score 1.

Step 5: Identify Precipitating Factors

Investigate both hepatic and extrahepatic precipitants 1:

• Hepatic: Heavy alcohol intake, viral hepatitis, drug-induced liver injury, autoimmune hepatitis
• Extrahepatic: Infections, hemorrhage, surgery, hemodynamic derangements

Note that in 40% of patients, no precipitant is identified 1, 4.

Critical Management Decisions Based on Scoring

ICU Admission Criteria

Patients with ACLF should ideally be admitted to intensive care or intermediate care units, with decisions based on ACLF grade, age, and comorbidities. 1

Patients with ACLF Grade 2-3 require ICU-level monitoring and organ support 2, 5.

Transplant Evaluation Timing

Patients suitable for liver transplantation should be referred to a transplant center early in the course of ACLF, as late referral may make transplantation impossible due to rapid disease evolution. 1

However, for patients with MELD ≥35 or very high CLIF-C ACLF scores, the risks of treatment-related complications (particularly respiratory failure) that could make them ineligible for transplant must be weighed carefully 6.

Futility Assessment

In patients with four or more organ failures after one week of adequate intensive treatment who are not transplant candidates, withdrawal of intensive care support can be considered due to futility. 7

A CLIF-C ACLF score >70 at 48-72 hours post-ICU admission indicates patients unlikely to benefit from ongoing intensive support 5.

Common Pitfalls and Caveats

Avoid Confusing ACLF with Acute Liver Failure

Do not diagnose ACLF in patients without preexisting chronic liver disease or cirrhosis—these patients have acute liver failure (ALF), which is a distinct entity with different management and prognosis. 8

MELD Underestimates Mortality in ACLF

MELD and MELD-Na scores may significantly underestimate mortality in ACLF because they capture intrinsic liver disease but do not account for extrahepatic organ failures. 1, 2 Always use ACLF-specific scores for prognostication.

Monitor for Respiratory Failure

Patients with ACLF Grade 3 or volume overload are at significantly increased risk of serious or fatal respiratory failure 6. Obtain baseline oxygen saturation before initiating any vasoactive therapy and monitor continuously with pulse oximetry 6.

Serial Reassessment is Essential

ACLF is a dynamic condition requiring frequent reassessment of organ function, as patients can rapidly progress or improve. 1, 7 Recalculate the CLIF-C ACLF score at Days 3-7 to assess trajectory 1.

Pre-ACLF Recognition

Patients with "pre-ACLF" (decompensated cirrhosis with elevated CRP and WBC, higher MELD scores, and more frequent complications) are at higher risk of developing ACLF and require closer monitoring, though no specific biomarkers accurately predict ACLF development 1, 2.