What are the diagnostic criteria and treatment options for acute liver disease?

Diagnostic Criteria and Treatment Options for Acute Liver Failure

Acute liver failure (ALF) is defined by the presence of coagulopathy and any degree of altered mental status in a patient without pre-existing liver disease, with illness duration ≤26 weeks. 1

Diagnostic Criteria

Definition and Classification

• ALF is characterized by rapid loss of functional hepatocytes in patients with no evidence of pre-existing liver disease 2
• The diagnostic criteria include:
  • Coagulopathy (INR ≥1.5)
  • Any degree of hepatic encephalopathy
  • Illness duration ≤26 weeks
  • No pre-existing liver disease 1, 3

Initial Laboratory Evaluation

• Complete blood count and ferritin levels should be obtained at baseline 4
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, total and direct bilirubin) 4, 1
• Coagulation studies (prothrombin time/INR) 1
• Renal function tests (creatinine, BUN, eGFR) 4
• Arterial blood gases and lactate 1
• Acetaminophen level and toxicology screen 1
• Viral hepatitis serologies 1

Imaging and Additional Testing

• Abdominal ultrasound is recommended as the first-line imaging test 5
• Transjugular liver biopsy may be helpful when etiology remains unclear after routine evaluation 4
• Neurological evaluation is often useful between attacks for assessment of positive neurological findings 4

Etiology-Specific Treatment Options

Acetaminophen-Induced ALF

• N-acetylcysteine (NAC) should be administered immediately at a loading dose of 140 mg/kg orally or via nasogastric tube followed by 70 mg/kg every 4 hours for 17 doses 1, 6
• NAC treatment should be initiated even if >48 hours since ingestion 1

Viral Hepatitis

• For hepatitis A and B-related ALF, supportive care is recommended as no virus-specific treatment has proven effective 1
• For patients with suspected herpes virus or varicella zoster as the cause of ALF, immediate acyclovir treatment is recommended 1

Wilson Disease

• Wilson disease-related ALF is considered uniformly fatal without transplantation 1
• Treatment to acutely lower serum copper and limit hemolysis should include albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange 1
• Penicillamine is not recommended in ALF due to risk of hypersensitivity 1

Autoimmune Hepatitis

• Liver biopsy should be considered to establish a diagnosis 1
• Treatment with corticosteroids (prednisone, 40-60 mg/day) is recommended 1
• Patients should be placed on the transplant list even while corticosteroids are being administered 1

Drug-Induced Hepatotoxicity

• Discontinue all but essential medications 1
• Obtain a detailed medication history including prescription drugs, non-prescription medications, herbs, and dietary supplements 1

Mushroom Poisoning

• Consider administration of penicillin G and silymarin 1
• Patients should be listed for transplantation, as this procedure is often the only lifesaving option 1

Supportive Care Management

Hemodynamic Support

• Careful attention must be paid to fluid resuscitation and maintenance of adequate intravascular volume 1
• If fluid replacement fails to maintain mean arterial pressure of 50-60 mm Hg, use systemic vasopressor support with agents such as epinephrine, norepinephrine, or dopamine (but not vasopressin) 1

Metabolic Management

• Manage hypoglycemia with continuous glucose infusions 1
• Monitor and supplement phosphate, magnesium, and potassium levels as needed 1
• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 1

Central Nervous System Management

• For grades III-IV encephalopathy, intubation is recommended for airway protection 1
• Control of seizures with phenytoin is advised, while avoiding benzodiazepines when possible 1

Coagulation Management

• Administration of vitamin K is recommended 1
• Fresh frozen plasma (FFP) should be reserved for invasive procedures or active bleeding 1
• Platelets should be given for counts <10,000/mm³ or before invasive procedures 1

Renal Support

• If dialysis support is needed for acute renal failure, use continuous modes rather than intermittent modes 1
• Nephrotoxic agents should be avoided 1

Liver Transplantation

• Urgent hepatic transplantation is indicated in ALF where prognostic indicators suggest a high likelihood of death 1
• Post-transplant survival rates for ALF have been reported as high as 80% to 90% 1
• Poor prognostic indicators include idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, and indeterminate cause 1

Common Pitfalls and Caveats

• Changes in aminotransferase levels correlate poorly with prognosis in ALF patients 1
• Malignant infiltration of the liver can mimic ALF and should be considered in patients with previous cancer history or massive hepatomegaly 4
• Systemic corticosteroids are ineffective for general ALF treatment, except in autoimmune hepatitis 1
• Sorbent systems may show transient improvement of hepatic encephalopathy but no improvement in hepatic function or long-term benefit 1