Definition of Liver Failure
Liver failure is defined as the impairment of one or more synthetic and/or excretory functions of the liver, which can manifest as prolonged prothrombin time, elevated serum lactate, decreased serum albumin, hypoglycemia, and/or hepatic encephalopathy. 1
Types of Liver Failure
Acute Liver Failure (ALF)
- Characterized by rapidly progressive liver dysfunction with a fall in prothrombin time (PT) ratio levels in patients without preexisting liver disease and developing in less than 26 weeks 1
- Severe ALF is defined by a PT ratio less than 50% (INR > 1.7) 1
- Serious ALF is defined by a PT ratio less than 50% combined with encephalopathy 1
- ALF is a rare condition with fewer than 10 cases per million persons per year in developed countries 1
Acute-on-Chronic Liver Failure (ACLF)
- Defined as a clinical syndrome of sudden hepatic decompensation in patients with chronic liver disease, associated with the failure of one or more extrahepatic organs 1
- According to EASL-CLIF Consortium definition, ACLF requires:
- Acute onset with rapid deterioration in clinical condition
- Presence of liver failure (elevated bilirubin and INR)
- At least one extrahepatic (neurologic, circulatory, respiratory, or renal) organ failure 1
Chronic Liver Failure
- End-stage form of chronic liver disease, typically cirrhosis 2
- Characterized by gradual replacement of healthy liver tissue by annular fibrosis, destroying liver architecture and blocking intrahepatic portal blood flow 1
Diagnostic Criteria
For Acute Liver Failure
- 50-50 criteria: PT index < 50% (INR > 1.7) and serum bilirubin > 50 μmol/L (2.9 mg/dl) on postoperative day 5 1
- International Study Group of Liver Surgery (ISGLS) grading system:
- Grade A: Postoperative deterioration not requiring change in clinical management
- Grade B: Change from regular postoperative clinical pattern requiring clinical intervention
- Grade C: Requiring invasive treatment 1
- King's College criteria:
- For paracetamol-induced ALF: pH < 7.3 or lactate > 3.5 mmol/L after fluid resuscitation, or three criteria: PT > 100 seconds, creatinine > 3.4 mg/dL, and encephalopathy grade III-IV 3
- For non-paracetamol ALF: PT > 100 seconds or three or more of: age < 10 or > 40 years, certain etiologies, jaundice > 7 days before encephalopathy, PT > 50 seconds, and bilirubin > 17 mg/dL 3
For ACLF
- CLIF-SOFA score evaluates:
- Liver function (bilirubin levels)
- Coagulation (INR)
- Cerebral function (encephalopathy grade)
- Renal function
- Circulatory function
- Respiratory function 3
Etiology
Causes of Acute Liver Failure
- Acetaminophen overdose (most common cause in Western countries) 4
- Drug-induced hepatotoxicity (antimicrobials, antiepileptics, statins) 4
- Viral hepatitis (A, B, E) 4
- Toxin exposure (mushroom poisoning, recreational drugs) 4
- Vascular causes (ischemic hepatitis, Budd-Chiari syndrome) 4
- Autoimmune hepatitis 3
Causes of Chronic Liver Disease Leading to ACLF
- Alcohol use disorder (approximately 45% of cirrhosis cases) 4
- Viral hepatitis B and C (hepatitis C accounts for 41% of cases) 4
- Metabolic dysfunction-associated fatty liver disease (MAFLD) 2, 4
- Genetic disorders (alpha-1 antitrypsin deficiency, hemochromatosis) 4
Clinical Manifestations
- Prolonged prothrombin time/elevated INR 1
- Elevated serum lactate 1
- Decreased serum albumin (hypoalbuminemia) 1
- Hypoglycemia 1
- Hepatic encephalopathy 1
- Jaundice (elevated bilirubin) 1, 3
- In ACLF: additional organ system failures (renal, circulatory, respiratory, cerebral) 1
Prognosis
- ALF mortality varies by etiology:
- When 50-50 criteria are met, there is a 59% risk of mortality compared to 1.2% when not met (sensitivity 70%, specificity 98%) 1
- ACLF has a 28-day mortality rate of 20% or more (vs. 5% or less among patients with acutely decompensated cirrhosis without ACLF) 1
Management Considerations
- Early contact with a transplant unit for ALF patients 4
- Systematic administration of N-acetylcysteine for ALF regardless of etiology 1, 4
- Empirical broad-spectrum antibiotics for signs of sepsis or worsening encephalopathy in ALF patients 4
- Continuous renal replacement therapy to control hyperammonaemia in severe cases 6
- Therapeutic plasma exchange may have a role in the sickest ALF patients 6, 7
- Liver transplantation when spontaneous recovery appears unlikely 4, 6