What are the stages of liver failure classification?

Stages of Liver Failure Classification

The classification of liver failure includes acute liver failure, acute-on-chronic liver failure, and end-stage liver disease, each with specific diagnostic criteria and grading systems that determine prognosis and guide management decisions. 1

Acute Liver Failure (ALF)

• ALF is defined as liver failure occurring within one month of the onset of jaundice in patients without pre-existing liver disease 2
• Based on the time interval between jaundice and encephalopathy, ALF can be further classified as:
  • Hyperacute liver failure: Encephalopathy within 7 days of jaundice onset (better prognosis despite high incidence of cerebral edema) 3
  • Acute liver failure: Encephalopathy between 8-28 days after jaundice onset (high incidence of cerebral edema, poor prognosis without transplantation) 3
  • Subacute liver failure: Encephalopathy between 5-12 weeks after jaundice onset (low incidence of cerebral edema but poor prognosis) 3

Acute-on-Chronic Liver Failure (ACLF)

• ACLF is defined as an acute decompensation of cirrhosis associated with one or more organ failures and high short-term mortality 1
• The diagnosis and severity classification is made using the CLIF-SOFA score, which evaluates organ failures 1
• ACLF is graded based on the number of organ failures:
  • ACLF Grade 1: Single organ failure 4
  • ACLF Grade 2: Two organ failures 4
  • ACLF Grade 3: Three or more organ failures 4
• ACLF is associated with a 28-day mortality rate of at least 15%, with 90-day mortality reaching approximately 58% 1

CLIF-SOFA Score Components

The CLIF-SOFA score evaluates the severity of organ failure across six systems 4:

1. Liver function: Based on bilirubin levels

   • <20 mmol/L (0 points)

   • 20-34 mmol/L (1 point)

   • 34-102 mmol/L (2 points)

   • 102-204 mmol/L (3 points)

   • 204 mmol/L (4 points) 4

2. Coagulation: Based on INR values

   • <1.1 (0 points)
   • 1.1-<1.25 (1 point)
   • 1.25-<1.5 (2 points)
   • 1.5-<2.5 (3 points)
   • ≥2.5 (4 points) 4

3. Cerebral function: Based on hepatic encephalopathy grade 4

4. Renal function: Based on creatinine levels 4

5. Circulatory function: Based on mean arterial pressure or vasopressor requirements 4

6. Respiratory function: Based on PaO2/FiO2 or SpO2/FiO2 ratio 4

Prognostic Criteria

King's College Criteria

1. For paracetamol-induced ALF:

   • pH arterial <7.3 or lactate arterial >3.5 mmol/L after fluid resuscitation, OR
   • Three criteria: prothrombin time >100 seconds, creatinine >3.4 mg/dL, and encephalopathy grade III-IV 4

2. For non-paracetamol ALF:

   • Prothrombin time >100 seconds, OR
   • Three or more of: age <10 or >40 years, non-A/non-B hepatitis or drug reaction, jaundice >7 days before encephalopathy, prothrombin time >50 seconds, bilirubin >17 mg/dL 4

Other Prognostic Indicators

• Age >40 years, serum bilirubin >15 mg/dL, prothrombin time >25 seconds, and cerebral edema are associated with poor outcomes 2
• Patients with ACLF grade 2-3 have significantly worse prognosis and should be considered for liver transplantation 4
• Patients with ALF who survive hospital discharge without transplant have a poor prognosis with 1-year survival less than 25% 4

Clinical Implications

• Early identification and transfer to a liver transplant center is crucial for management 4
• Patients with rising bilirubin and ACLF should be admitted to intensive care units for close monitoring 4
• Identification and treatment of precipitating factors (infections, GI bleeding, drug toxicity, viral hepatitis) is essential 4
• Organ support should be provided based on the specific organ failures present 4
• Liver transplantation evaluation should be initiated early for appropriate candidates 4

Pitfalls in Classification

• Multiple definitions of ACLF exist depending on geographical location, leading to confusion in diagnosis and management 1
• The Asian Pacific Association for the Study of the Liver (APASL), European Association for the Study of Chronic Liver Failure (EASL-CLIF), and North American Consortium for the Study of End-Stage Liver Disease (NACSELD) criteria may characterize different stages of the same condition 1
• Isolated laboratory abnormalities should be interpreted in the context of clinical presentation and other parameters 4
• Bilirubin may be falsely elevated in patients with hemolysis, which should be excluded when evaluating liver failure 4

By understanding these classification systems and their prognostic implications, clinicians can better identify patients at highest risk and implement appropriate management strategies, including early consideration for liver transplantation when indicated.