What is the definition of chronic hepatic failure?

Definition of Chronic Hepatic Failure

Chronic hepatic failure is defined as a progressive deterioration of liver function characterized by elevated bilirubin, increased INR, and the development of complications of portal hypertension in patients with underlying chronic liver disease, which can lead to acute-on-chronic liver failure when precipitating events cause rapid deterioration and extrahepatic organ failures. 1, 2

Key Components of Chronic Hepatic Failure

• Underlying chronic liver disease: The foundation of chronic hepatic failure is pre-existing chronic liver disease, which may be initially asymptomatic but progressively impairs liver structure and function 3

• Progressive deterioration: Unlike acute liver failure, chronic hepatic failure involves gradual worsening of liver function over time, with potential for acute deterioration

• Laboratory abnormalities:

  • Elevated bilirubin (jaundice)
  • Increased International Normalized Ratio (INR) indicating coagulopathy
  • Abnormal liver enzymes

• Clinical manifestations:

  • Ascites
  • Hepatic encephalopathy
  • Gastrointestinal bleeding (from varices)
  • Jaundice
  • Hepatorenal syndrome

Progression to Acute-on-Chronic Liver Failure (ACLF)

Chronic hepatic failure can progress to ACLF, which is characterized by:

1. Acute deterioration with rapid worsening of clinical condition
2. Liver failure defined by elevated bilirubin and INR
3. At least one extrahepatic organ failure (neurologic, circulatory, respiratory, or renal) 1

Different Regional Definitions of ACLF

• EASL-CLIF definition: Classifies ACLF into grades 1-3 based on number and type of organ failures; includes patients at intermediate stage of disease 1, 2

• APASL definition: Focuses on early stage disease; includes patients with chronic liver disease without cirrhosis 1, 2

• NACSELD definition: Includes only patients with two or more extrahepatic organ failures (often preterminal stage) 1, 2

Common Precipitants of Acute Deterioration

Chronic hepatic failure can acutely worsen due to:

• Bacterial infections (most common precipitant, 48% of cases) 2
• Severe alcoholic hepatitis 2
• Gastrointestinal bleeding 2
• Viral hepatitis exacerbation (particularly hepatitis B in Asian populations) 2
• Surgery 4
• No identifiable precipitant (in >40% of cases) 4

Prognostic Considerations

• Mortality in chronic hepatic failure increases dramatically when progression to ACLF occurs
• 28-day mortality rate is ≥20% in ACLF, compared to ≤5% in decompensated cirrhosis without ACLF 2
• The number of precipitating factors present simultaneously significantly impacts short-term prognosis 2
• Patients with two or more precipitants have significantly higher 90-day mortality 2

Clinical Stages of Chronic Liver Disease

Chronic hepatic failure typically follows a progression:

1. Compensated cirrhosis: No complications
2. Decompensated cirrhosis: Manifestations of portal hypertension complications
3. Acute-on-chronic liver failure: Rapid deterioration with organ failures 1

Pathophysiological Features

• Systemic inflammation: Characteristic feature of progression to ACLF 4
• Increased susceptibility to infection: Common in advanced chronic hepatic failure 4
• Multi-organ dysfunction: Progressive involvement of extrahepatic organs 5, 6

The definition and understanding of chronic hepatic failure are important for early identification of patients at risk for rapid deterioration and for implementing appropriate therapeutic interventions to improve outcomes.