What are the causes and management of liver failure?

Causes and Management of Liver Failure

The main causes of liver failure include acetaminophen toxicity (most common at 22%), viral hepatitis (14.6%), drug-induced liver injury (9.4%), alcoholic hepatitis, autoimmune hepatitis, ischemic injury, and Budd-Chiari syndrome, with treatment varying by etiology but often requiring N-acetylcysteine therapy and consideration for liver transplantation in severe cases. 1

Classification of Liver Failure

Liver failure can be classified into two main categories:

1. Acute Liver Failure (ALF): Develops in patients without pre-existing liver disease
2. Acute-on-Chronic Liver Failure (ACLF): Acute decompensation in patients with cirrhosis

Detailed Causes of Liver Failure

Drug-Induced Liver Failure

• Acetaminophen toxicity: Most common cause of ALF in the US
  • Requires immediate N-acetylcysteine therapy without waiting for serum levels 2
  • Recommendation: "In patients with acetaminophen-induced acute liver failure, we recommend the initiation of N-acetylcysteine therapy without waiting for, and regardless of, the results of serum acetaminophen determinations" 2
• Other medications: Antimicrobials, antiepileptics, statins (9.4% of cases) 2
• Herbal supplements: Various herbal products and dietary supplements 1

Viral Hepatitis

• Hepatitis A and B: Account for approximately 14.6% of ALF cases 2
• Hepatitis B reactivation: Risk during chemotherapy or immunosuppression
  • Recommendation: "Nucleoside analogs should be given prior to and continued for 6 months after completion of chemotherapy in patients with Hepatitis B surface antigen positivity" 2
• Hepatitis E: Significant cause in endemic countries, particularly dangerous in pregnant women 2
• Herpes viruses: Rare cause, more common in immunosuppressed patients and pregnant women
  • Recommendation: "Patients with known or suspected herpes virus or varicella zoster as the cause of acute liver failure must be immediately placed on the liver transplant list" 2

Autoimmune Hepatitis

• Recommendation: "Patients with acute liver failure due to autoimmune hepatitis should be treated with corticosteroids (prednisone, 40-60 mg/day)" 2
• Patients should be listed for transplantation even while receiving corticosteroids 2

Vascular Causes

• Ischemic injury ("shock liver"): Due to cardiac arrest, hypotension, or severe heart failure
  • Recommendation: "In ALF patients with evidence of ischemic injury cardiovascular support is the treatment of choice" 2
• Budd-Chiari syndrome: Hepatic vein thrombosis
  • Recommendation: "Hepatic vein thrombosis with hepatic failure is an indication for liver transplantation, provided underlying malignancy is excluded" 2

Pregnancy-Related

• Acute fatty liver of pregnancy/HELLP syndrome
  • Recommendation: "For acute fatty liver of pregnancy or the HELLP syndrome, consultation with obstetrical services and expeditious delivery are recommended" 2

Other Causes

• Wilson disease: Copper overload disorder, uniformly fatal without transplantation 2
• Malignant infiltration: Breast cancer, small cell lung cancers, lymphoma, melanoma 2
• Indeterminate etiology: Up to 25% of cases remain undiagnosed despite extensive investigation 2

Management Approach to Liver Failure

General Management

1. Etiology-specific treatment:

   • Acetaminophen toxicity: N-acetylcysteine therapy 2
   • Viral hepatitis: Supportive care, consider antivirals for specific types 2
   • Herpes virus: Acyclovir 2
   • Autoimmune hepatitis: Corticosteroids 2

2. Supportive care:

   • Avoid sedatives such as benzodiazepines and psychotropic drugs 2
   • Avoid nephrotoxic drugs, including NSAIDs 2
   • Do not routinely correct coagulation unless active bleeding 2
   • Do not use treatments (lactulose, rifaximin) to lower ammonia levels 2

3. Infection prevention and management:

   • Empirical broad-spectrum antibiotics for patients with worsening hepatic encephalopathy or signs of SIRS 2
   • Bacterial infections documented in 60-80% of ALF patients 2

4. Monitoring and correction of metabolic abnormalities:

   • Monitor glucose levels every 2 hours (hypoglycemia is common) 2
   • Target sodium levels between 140-145 mmol/L 2
   • Correct electrolyte disturbances, particularly phosphate 2

Liver Transplantation Considerations

• Early referral for transplant evaluation is crucial
• Conditions with poor transplant-free survival (<25%):
  • Hepatitis B
  • Drug-induced liver injury (non-acetaminophen)
  • Autoimmune hepatitis
  • Wilson disease
  • Budd-Chiari syndrome 2

Prognosis

• Transplant-free survival of patients with ALF related to acetaminophen, hepatitis A, hypoxic hepatitis, or pregnancy is approximately 50% 2
• ACLF grade based on organ failure better predicts outcomes than standard prognostic methods like MELD or Child-Pugh scores 2
• CLIF-C ACLF score > 70 is associated with approximately 90% 90-day mortality 1

Common Pitfalls and Caveats

• Failure to recognize acetaminophen toxicity early and delay in N-acetylcysteine administration
• Missing herpes virus hepatitis, which requires specific antiviral therapy
• Overlooking pregnancy-related causes in women of childbearing age
• Delayed referral for liver transplantation evaluation
• Inadequate monitoring for cerebral edema in ALF patients
• Inappropriate use of sedatives or lactulose in ALF patients 2, 1

By understanding the diverse causes of liver failure and implementing appropriate management strategies, clinicians can improve outcomes for these critically ill patients.