What are the manifestations of severe liver failure?

Manifestations of Severe Liver Failure

Severe liver failure presents with coagulopathy (INR ≥1.5 or PT <50%), hepatic encephalopathy, and metabolic derangements including hypoglycemia and hyponatremia, often accompanied by multi-organ dysfunction. 1

Core Defining Features

Coagulation Abnormalities

• Prolonged prothrombin time with INR ≥1.5 is the laboratory hallmark that defines acute liver failure when combined with altered mental status 1, 2
• Severe acute liver failure is specifically defined by PT ratio <50% (or Factor V <50%) 1
• Thrombocytopenia commonly accompanies the coagulopathy 2
• Despite laboratory abnormalities, most patients maintain rebalanced hemostasis between pro- and anticoagulant factors 2

Hepatic Encephalopathy

• Any degree of mental alteration—from subtle confusion to coma—is required for the diagnosis 1
• Encephalopathy should be monitored frequently as it progresses hour-by-hour 1
• Grade 3-4 encephalopathy is associated with cerebral edema in 38-81% of patients 1
• Neurological symptoms correlate with survival: 90.1% survival without encephalopathy versus 37.8% with encephalopathy 1

Metabolic Derangements

• Hypoglycemia requires blood glucose monitoring at least every 2 hours 1, 2
• Hyponatremia (sodium <130 mmol/L) is common and correlates with intracranial pressure 2
• Maintain serum sodium between 140-145 mmol/L to prevent cerebral edema 1
• Depletion of potassium, magnesium, and phosphate occurs frequently 1, 2

Clinical Presentation Patterns

Physical Examination Findings

• Jaundice is often but not always present at presentation 1
• Deep jaundice with elevated bilirubin and disproportionately low alkaline phosphatase, particularly in Wilson disease 2
• Right upper quadrant tenderness is variably present 1
• Inability to palpate the liver or percuss significant dullness suggests massive hepatocyte loss 1
• Enlarged liver may indicate viral hepatitis, malignant infiltration, congestive heart failure, or Budd-Chiari syndrome 1

Laboratory Abnormalities

• Markedly elevated aminotransferases (AST/ALT) 1, 2
• Elevated arterial lactate (>3.5 mmol/L at 4 hours or >3.0 mmol/L at 12 hours indicates poor prognosis) 1
• Elevated arterial ammonia (sustained levels 150-200 mmol/L increase risk of intracranial hypertension) 1
• Elevated bilirubin (thresholds 140-200 mmol/L have prognostic significance) 1

Multi-Organ System Failures

Cardiovascular Manifestations

• Hypotension and circulatory collapse requiring vasopressor support 1, 3
• Right or left cardiac dysfunction can develop 1
• Mean arterial pressure <70 mmHg indicates circulatory system failure 4
• Evidence of adrenal dysfunction in 50% of patients 1

Renal Manifestations

• Acute kidney injury frequently accompanies acute liver failure 1, 2
• Rising serum creatinine (≥2 mg/dl) indicates kidney system failure 4
• Hepatorenal syndrome can develop 2, 4
• Creatinine >300 μmol/L combined with other factors indicates poor prognosis 1

Respiratory Manifestations

• Decreasing PaO2/FiO2 ratio (≤300) indicates respiratory system failure 4
• Hypoxemia requiring supplemental oxygen 4
• Mechanical ventilation required in 56-66% of patients 5

Neurological Manifestations

• Cerebral edema with raised intracranial pressure occurs particularly in hyperacute and acute presentations 2
• Correlation between hyponatremia and intracranial pressure 2
• Progression occurs hour-by-hour, requiring intensive monitoring 1

Infectious Complications

• Bacterial infections documented in 60-80% of acute liver failure patients 2
• Fungal infections occur in one-third of patients 2
• Spontaneous bacterial peritonitis is a critical precipitating event 4
• Empirical broad-spectrum antibiotics indicated for worsening encephalopathy or signs of SIRS 1

Hematologic Manifestations

• Coombs-negative hemolytic anemia may be the only initial symptom in Wilson disease 2
• Marked hemolysis commonly associated with severe liver disease 2

Gastrointestinal Manifestations

• Variceal hemorrhage can occur as acute precipitating event 4
• Ascites may develop, though its presence suggests underlying chronic liver disease 1

Systemic Inflammatory Response

• Elevated white blood cell count 4
• Elevated C-reactive protein levels 4

Critical Pitfalls to Avoid

• Do not confuse hepatic encephalopathy with hypoglycemia clinically—both present with altered mental status, necessitating frequent glucose monitoring 2
• Do not overlook subtle alterations in mentation—any degree of mental change with INR ≥1.5 establishes the diagnosis 1
• Do not delay transfer to ICU—changes in consciousness occur hour-by-hour 1
• Do not fail to recognize early signs of infection, which precipitate rapid deterioration 4
• Do not assume jaundice is always present—it is often but not invariably seen 1