What is decompensated liver failure?

Decompensated Liver Failure: Definition, Pathophysiology, and Clinical Implications

Decompensated liver failure is defined as the progression of chronic liver disease to a state characterized by the development of overt clinical complications including ascites, gastrointestinal bleeding, hepatic encephalopathy, and jaundice, marking the transition from compensated to decompensated cirrhosis with significantly increased mortality risk. 1

Definition and Classification

Decompensated liver failure represents a critical stage in the natural history of cirrhosis, characterized by:

• The emergence of clinical complications that were previously absent in the compensated phase
• Significant deterioration in liver function and portal hypertension
• Marked reduction in survival (median survival decreases from >12 years in compensated cirrhosis to approximately 2 years after decompensation) 1, 2

The progression of liver disease typically follows three distinct stages:

1. Compensated cirrhosis: Asymptomatic phase with preserved liver function
2. Decompensated cirrhosis: Development of overt clinical complications
3. Further decompensation/ACLF: Characterized by additional decompensating events, recurrent complications, or development of acute-on-chronic liver failure 1

Pathophysiological Mechanisms

The pathophysiology of decompensated liver failure involves several interconnected mechanisms:

1. Portal Hypertension and Circulatory Dysfunction

• Progressive increase in portal pressure leads to splanchnic vasodilation
• Development of hyperdynamic circulation with decreased effective arterial blood volume
• Activation of vasoconstrictor systems causing sodium and water retention 1

2. Systemic Inflammation

• Bacterial translocation from the gut due to intestinal dysbiosis and increased intestinal permeability
• Release of pathogen-associated molecular patterns (PAMPs) into circulation
• Production of danger-associated molecular patterns (DAMPs) from the diseased liver
• Activation of immune cells leading to pro-inflammatory cytokine release 1, 3

3. Multi-Organ Dysfunction

• Circulatory dysfunction contributes to renal sodium retention and ascites
• Impaired cardiac response (cirrhotic cardiomyopathy) worsens effective hypovolemia
• Progressive development of hepatorenal syndrome, hepatopulmonary syndrome, and other organ failures 1

Clinical Manifestations

The hallmark clinical manifestations of decompensated liver failure include:

• Ascites: Accumulation of fluid in the peritoneal cavity due to portal hypertension and sodium retention
• Variceal bleeding: Hemorrhage from esophageal or gastric varices due to portal hypertension
• Hepatic encephalopathy: Neuropsychiatric abnormalities due to impaired liver detoxification
• Jaundice: Yellow discoloration of skin/sclera due to hyperbilirubinemia
• Hepatorenal syndrome: Progressive renal dysfunction in advanced liver disease 1, 2

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

Decompensated liver failure may progress to ACLF, which is characterized by:

• Acute onset with rapid deterioration in clinical condition
• Presence of liver failure (elevated bilirubin and INR)
• Development of one or more extrahepatic organ failures (neurologic, circulatory, respiratory, or renal)
• High short-term mortality (28-day mortality of 30-50%) 1, 2

The American Association for the Study of Liver Diseases (AASLD) defines ACLF as requiring all three elements:

1. Acute onset with rapid deterioration
2. Liver failure with elevated bilirubin and INR
3. At least one extrahepatic organ failure 1

Common Precipitants of Decompensation

Several factors can precipitate decompensation in patients with chronic liver disease:

• Bacterial infections (particularly spontaneous bacterial peritonitis)
• Alcoholic hepatitis (in alcohol-related liver disease)
• Gastrointestinal bleeding with hemodynamic instability
• Viral hepatitis reactivation or superinfection
• Drug-induced liver injury 2

Management Approaches

The management of decompensated liver failure involves two main approaches:

1. Treating the underlying etiology:

   • Abstinence from alcohol in alcoholic liver disease
   • Antiviral therapy in viral hepatitis
   • Removal of hepatotoxic medications

2. Managing specific complications:

   • Ascites: Sodium restriction, diuretics, large-volume paracentesis with albumin
   • Variceal bleeding: Vasoactive drugs, endoscopic therapy
   • Hepatic encephalopathy: Lactulose, rifaximin
   • Spontaneous bacterial peritonitis: Antibiotics and albumin
   • Hepatorenal syndrome: Vasoconstrictors (terlipressin, norepinephrine) with albumin 1

Prognosis and Outcomes

The development of decompensation significantly worsens prognosis:

• Median survival decreases from >12 years in compensated cirrhosis to approximately 2 years after decompensation
• Progression to ACLF further increases mortality risk (28-day mortality of 30-50%)
• The number and type of organ failures in ACLF determine prognosis
• Liver transplantation may be the only definitive treatment for selected patients 1

Clinical Pitfalls and Caveats

• Decompensation can occur through two distinct pathways: non-acute (gradual) or acute (rapid deterioration) 4
• The clinical presentation of infection in cirrhosis can be subtle, with fever often absent
• Traditional markers of infection may be altered by underlying liver disease
• Multiple simultaneous precipitating factors significantly worsen prognosis 2
• Terlipressin (used for hepatorenal syndrome) is contraindicated in patients with hypoxemia and ongoing coronary, peripheral, or mesenteric ischemia 1

Understanding decompensated liver failure as a distinct clinical entity with specific pathophysiological mechanisms is crucial for appropriate management and improving outcomes in these critically ill patients.