What are the causes and treatments of liver failure?

Causes of Liver Failure

The main causes of liver failure include acetaminophen toxicity, viral hepatitis, drug-induced liver injury, 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:

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

Causes of Acute Liver Failure

Drug-Induced Liver Injury

• Acetaminophen toxicity: Most common cause of ALF in the United States (22% of cases requiring transplantation) 1
  • Treatment: N-acetylcysteine therapy should be initiated immediately without waiting for serum acetaminophen levels 1
• Other medications: Antimicrobials, antiepileptics, statins (9.4% of cases) 1
• Herbal supplements: Various herbal preparations can cause liver injury 1

Viral Hepatitis

• Hepatitis A and B: Account for approximately 14.6% of ALF cases 1
  • Hepatitis B reactivation can occur during chemotherapy or immunosuppression
  • Prophylactic nucleoside analogs recommended for HBsAg-positive patients undergoing immunosuppressive therapy 1
• Hepatitis E: Significant cause in endemic countries, more severe in pregnant women 1
• Herpes viruses: Rare cause of ALF, more common in immunosuppressed patients and pregnant women
  • Treatment: Acyclovir for suspected or documented cases 1

Autoimmune Hepatitis

• Can present as ALF requiring immunosuppressive therapy

Vascular Causes

• Ischemic injury ("shock liver"): Following cardiac arrest, hypotension, or severe heart failure
  • Treatment: Cardiovascular support is primary 1
• Budd-Chiari syndrome: Hepatic vein thrombosis
  • Diagnosis: Confirmed with imaging (CT, Doppler ultrasound, venography)
  • Treatment: May require liver transplantation if significant liver failure develops 1

Pregnancy-Related

• Acute fatty liver of pregnancy
• HELLP syndrome
  • Treatment: Consultation with obstetrics and expeditious delivery 1

Malignant Infiltration

• Breast cancer, small cell lung cancers, lymphoma, melanoma
• Presents with massive hepatic enlargement
• Diagnosis: Imaging and liver biopsy 1

Metabolic Disorders

• Wilson disease: Copper overload disorder
• Various inborn errors of metabolism

Indeterminate Etiology

• Despite extensive evaluation, cause remains unknown in approximately 25% of cases 1
• Transjugular liver biopsy may help identify etiology 1

Causes of Acute-on-Chronic Liver Failure (ACLF)

Cirrhosis Etiologies

• Alcoholic liver disease: Most common cause
• Viral hepatitis (B and C)
• Non-alcoholic fatty liver disease (NAFLD/NASH): Leading cause of hepatic fibrosis worldwide 2

Precipitating Factors for ACLF

• Bacterial infections
• Alcoholic hepatitis
• Gastrointestinal bleeding
• Hepatitis B virus flare 3

Treatment Approaches

General Management

1. N-acetylcysteine therapy:

   • Recommended for acetaminophen-induced ALF 1
   • Also beneficial in non-acetaminophen ALF to improve transplant-free survival 1

2. Intensive care management:

   • Patients with ALF or ACLF should be admitted to ICU or intermediate care units 1
   • Monitor for and treat complications: cerebral edema, hypoglycemia, coagulopathy

3. Specific treatments based on etiology:

   • Viral hepatitis: Nucleoside analogs for hepatitis B
   • Herpes virus: Acyclovir
   • Autoimmune hepatitis: Corticosteroids
   • Pregnancy-related: Delivery
   • Ischemic: Cardiovascular support

4. Liver transplantation consideration:

   • Early referral to transplant centers is critical 4
   • Particularly important for mushroom poisoning, Wilson disease, and Budd-Chiari syndrome 1

Palliative Care

• For patients with poor prognosis who are not transplant candidates
• Especially when multiple organ failures persist despite adequate treatment 4

Prognostic Indicators

• CLIF-C ACLF score > 70 associated with approximately 90% 90-day mortality 4
• Four or more organ failures at Days 3-7 after ACLF diagnosis associated with 100% 90-day mortality 4

Prevention

• For NAFLD/NASH-related liver disease: Lifestyle modifications (weight loss, exercise, healthy diet) 2
• For hepatitis B reactivation: Prophylactic nucleoside analogs during immunosuppression 1
• Early identification and treatment of precipitating factors in cirrhotic patients

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