What are the diagnostic criteria for Acute-on-Chronic Liver Failure (ACLF)?

Diagnostic Criteria for Acute-on-Chronic Liver Failure (ACLF)

The diagnosis of ACLF should be made in patients with cirrhosis and acute decompensation when organ failure(s) associated with high short-term mortality develop, based on the CLIF-C Organ Failure scoring system. 1

Definition and Core Concepts

• ACLF is characterized by acute deterioration of liver function in patients with pre-existing chronic liver disease, resulting in hepatic and extrahepatic organ failures with high short-term mortality (28-day mortality ranging from 30-50%) 1, 2
• The syndrome requires an acute insult or precipitating event in the setting of cirrhosis or chronic liver disease, leading to rapid progression to multiorgan failure 1, 3
• Different diagnostic criteria have been established by major international societies, with the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) focusing on organ failures in cirrhotic patients 1, 4

EASL-CLIF Diagnostic Criteria

The EASL-CLIF criteria for ACLF diagnosis and grading are based on the CLIF-Sequential Organ Failure Assessment (CLIF-SOFA) score, which evaluates six organ systems 1:

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

ACLF Grading System

ACLF is classified into the following grades based on organ failures 1:

• 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
• 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

Prognostic Significance

• ACLF Grade 1: 28-day mortality rate of approximately 23%
• ACLF Grade 2: 28-day mortality rate of approximately 32%
• ACLF Grade 3: 28-day mortality rate of approximately 78% 1

Precipitating Factors

• Potential precipitating factors should be investigated, including 1:
  • Hepatic factors: Heavy alcohol intake, viral hepatitis, drug-induced liver injury, autoimmune hepatitis
  • Extrahepatic factors: Infections, hemodynamic derangements following hemorrhage, surgery
• In approximately 40% of cases, no precipitating factor can be identified 1, 5

Pathophysiological Basis

• ACLF develops in the setting of systemic inflammation, with severity correlating with the number of organ failures and mortality 5
• The syndrome involves complex mechanisms including exaggerated inflammatory response and systemic oxidative stress to pathogen- or damage-associated molecular patterns 6, 5

Prognostic Scoring Systems

• The CLIF-C ACLF score incorporates the CLIF-C Organ Failure score, age, and white blood cell count: 10 × [0.033 × CLIF-OFs + 0.04 × Age + 0.63 × Ln(WBC)²] 1
• This score provides better prognostic accuracy than traditional scoring systems like MELD or MELD-Na in ACLF patients 1
• Serial assessment (particularly at days 3-7) provides better prognostic information than a single evaluation at diagnosis 1

Clinical Implications and Management

• Patients with ACLF should ideally be admitted to intensive care or intermediate care units 1
• Early identification and treatment of precipitating factors is crucial, particularly for infections, GI bleeding, drug toxicity, or viral hepatitis reactivation 1, 7
• Treatment is based on organ support and management of associated complications, as there is no specific effective treatment for ACLF 1
• Liver transplantation should be considered in selected patients 1, 5
• Terlipressin should be avoided in patients with ACLF Grade 3 due to significant risk of respiratory failure 8

Important Caveats and Pitfalls

• Different definitions exist globally - the Asian Pacific Association for the Study of the Liver (APASL) criteria focus more on liver failure parameters and include non-cirrhotic chronic liver disease patients 4
• ACLF is a dynamic condition requiring sequential assessment rather than a single time point evaluation 1
• Traditional scoring systems like MELD may underestimate mortality in ACLF as they don't account for all extrahepatic organ failures 1
• Patients with fluid overload may be at increased risk of respiratory failure, requiring careful management of volume status 8