What are the signs of liver cell failure?

Signs of Liver Cell Failure

Liver cell failure presents with a constellation of clinical and biochemical abnormalities reflecting profound hepatocyte dysfunction, including coagulopathy (INR ≥1.5), hepatic encephalopathy, jaundice, hypoglycemia, and electrolyte disturbances, with the specific pattern varying based on whether the presentation is acute, acute-on-chronic, or chronic decompensated. 1, 2

Core Clinical Features

Coagulopathy

• Prolonged prothrombin time/INR ≥1.5 is a defining feature, reflecting impaired hepatic synthesis of clotting factors 2, 3
• Unresponsive to parenteral vitamin K administration in severe cases 1
• Thrombocytopenia commonly accompanies coagulopathy 1
• Despite laboratory abnormalities, most patients maintain rebalanced hemostasis between pro- and anticoagulant factors 1

Hepatic Encephalopathy

• Altered mental status ranging from subtle confusion to coma 1, 2
• Required for diagnosis of acute liver failure in adults (though not in children) 4
• Can be confused with hypoglycemia clinically, necessitating frequent glucose monitoring 1
• Worsening encephalopathy may signal sepsis or disease progression 1

Jaundice and Biochemical Abnormalities

• Deep jaundice with elevated bilirubin is characteristic 1
• Elevated aminotransferases (AST/ALT), though levels vary by etiology 1
• Disproportionately low or normal alkaline phosphatase relative to bilirubin, particularly in Wilson's disease (ratio of alkaline phosphatase to bilirubin <2) 1
• In acute presentations, transaminases may be only modestly elevated (typically <2,000 IU/L) despite severe liver dysfunction 1

Metabolic Derangements

• Hypoglycemia is a well-recognized complication requiring blood glucose monitoring at least every 2 hours 1
• Hyponatremia (sodium <130 mmol/L) is common and correlates with intracranial pressure 1
• Depletion of potassium, magnesium, and phosphate 1
• Hyperammonemia contributing to encephalopathy 1

Presentation Patterns by Clinical Context

Acute Liver Failure (Previously Healthy Liver)

• Rapid onset over days to weeks in patients without pre-existing chronic liver disease 2, 5
• Coagulopathy (INR ≥1.5) plus encephalopathy define the syndrome 2, 3
• Hyperacute (<7 days jaundice to encephalopathy): high cerebral edema risk but better survival with medical management 5
• Acute (8-28 days): high cerebral edema risk with poor prognosis without transplantation 5
• Subacute (5-12 weeks): low cerebral edema risk but poor prognosis 5

Wilson's Disease Acute Presentation

• Coombs-negative hemolytic anemia with acute intravascular hemolysis 1
• Rapid progression to renal failure 1
• Relatively modest aminotransferase elevations from onset 1
• Markedly subnormal alkaline phosphatase (typically <40 IU/L) 1
• Female predominance (4:1 ratio) 1
• May present during delivery mimicking HELLP syndrome 1

Acute-on-Chronic Liver Failure (ACLF)

• Organ system failures (liver, kidney, brain, coagulation, circulation, respiration) in patients with cirrhosis 1
• 28-day mortality ≥20% (versus ≤5% in decompensated cirrhosis without ACLF) 1
• Triggered by precipitants including infection with sepsis, severe alcohol-related hepatitis, or clinically inapparent events 1

Decompensated Chronic Liver Disease

• Ascites, variceal hemorrhage, or hepatic encephalopathy in patients with known cirrhosis 1, 6
• Median survival drops to 1.8 years once decompensation occurs 6
• Isolated splenomegaly may indicate clinically inapparent cirrhosis with portal hypertension 1
• Hepatomegaly/splenomegaly, edema, hemorrhagic diathesis 1

Associated Complications

Renal Dysfunction

• Acute kidney injury frequently accompanies acute liver failure 1
• Hepatorenal syndrome in chronic liver disease 1
• Electrolyte disturbances require monitoring and correction 1

Hemolysis

• Coombs-negative hemolytic anemia may be the only initial symptom in Wilson's disease 1
• Marked hemolysis commonly associated with severe liver disease 1
• Release of stored copper from dying hepatocytes aggravates hemolysis 1
• Low hemoglobin with low cholinesterase suggests acute Wilson's disease 1

Infection Susceptibility

• Bacterial infections documented in 60-80% of acute liver failure patients 1
• Fungal infections occur in one-third of patients 1
• Worsening encephalopathy may signal sepsis 1

Cerebral Complications

• Cerebral edema with raised intracranial pressure, particularly in hyperacute and acute presentations 5
• Correlation between hyponatremia and intracranial pressure 1

Critical Diagnostic Pitfalls

Do not assume all jaundice with coagulopathy represents acute liver failure—carefully distinguish between acute liver failure (no pre-existing disease), acute-on-chronic liver failure (cirrhosis with organ failures), and decompensated cirrhosis (complications without organ failure), as prognosis and management differ substantially 1, 6

In young patients with apparent acute hepatitis, always consider Wilson's disease, especially with deep jaundice, hemolysis, low alkaline phosphatase, and modest transaminase elevations 1

Hypoglycemia can mimic hepatic encephalopathy—monitor glucose at least every 2 hours to avoid missing this treatable complication 1

Prophylactic correction of coagulopathy precludes assessment of disease evolution—reserve factor replacement for active bleeding or high-risk procedures 1