What is the initial management for acute liver disease?

Initial Management of Acute Liver Disease

All patients with acute liver failure (ALF) must be admitted immediately to an intensive care unit with continuous monitoring, and early contact with a liver transplant center should be initiated within hours of recognition. 1, 2

Immediate Diagnostic Workup

Upon recognition of coagulopathy (INR ≥1.5) with any degree of altered mental status in a patient without preexisting cirrhosis, obtain the following laboratory tests immediately 1, 2:

• Coagulation parameters: Prothrombin time/INR to confirm diagnosis and assess severity 1
• Acetaminophen level: Essential even without clear history of ingestion, as this is the most common cause and has specific antidotal therapy 1, 2
• Comprehensive metabolic panel: Sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate, glucose, creatinine, BUN 1, 2
• Liver function tests: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin 1, 2
• Arterial blood gases and lactate: Critical for assessing severity and prognosis 1
• Complete blood count with ferritin: To assess for hemochromatosis and baseline hematologic status 1, 2
• Viral hepatitis serologies: Anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV 1
• Toxicology screen: Urine screen for amphetamines, cocaine, and other substances 1
• Ceruloplasmin and 24-hour urine copper: If patient is under 40 years old without obvious etiology (to evaluate for Wilson disease) 1, 2
• Autoimmune markers: ANA, ASMA, immunoglobulin levels if autoimmune hepatitis suspected 1, 2
• Pregnancy test: In all females of childbearing age 1
• Arterial ammonia: For prognostic assessment 1

Immediate Imaging Studies

• Hepatic Doppler ultrasound: Perform immediately to exclude chronic liver disease, verify vessel patency, and rule out Budd-Chiari syndrome 1, 2
• Echocardiography: Assess cardiac function, especially when ischemic injury is suspected 1, 2

Critical Initial Therapeutic Interventions

N-Acetylcysteine Administration

Administer N-acetylcysteine (NAC) immediately in ALL patients with suspected or confirmed acetaminophen toxicity, regardless of time since ingestion. 1, 2 NAC should also be given when acetaminophen ingestion is possible or when circumstances surrounding admission are inadequate 1, 2. Recent guidelines from the European Association for the Study of the Liver recommend systematic administration of NAC whatever the suspected etiology 1.

Dosing regimens 1, 2:

• Oral/nasogastric: 140 mg/kg loading dose, followed by 70 mg/kg every 4 hours for 17 doses 1, 2
• Intravenous: 150 mg/kg in 5% dextrose over 15 minutes, then 50 mg/kg over 4 hours, followed by 100 mg/kg over 16 hours 1
• If presentation is within 4 hours of acetaminophen ingestion, give activated charcoal (1 g/kg orally) just prior to starting NAC 1, 2

Hemodynamic Stabilization

Maintain mean arterial pressure ≥50-60 mmHg through aggressive fluid resuscitation as first-line intervention. 1, 2

• Fluid choice: Colloid (albumin) is preferred over crystalloid, and all solutions should contain dextrose to maintain euglycemia 2
• Vasopressor support: If fluid replacement fails to maintain adequate MAP, use norepinephrine, epinephrine, or dopamine—but NOT vasopressin 1, 2
• Consider pulmonary artery catheterization in hemodynamically unstable patients 1, 2

Metabolic Management

• Hypoglycemia: Monitor blood glucose at least every 2 hours and manage with continuous glucose infusions 1, 2, 3
• Electrolyte monitoring: Supplement phosphate, magnesium, and potassium as needed 1, 3
• Serum sodium: Maintain levels between 140-145 mmol/L to prevent cerebral edema 1, 2

Etiology-Specific Immediate Treatments

Herpes Simplex Virus or Varicella Zoster

Administer acyclovir immediately if HSV or VZV hepatitis is suspected (e.g., presence of fever with ALF), and place patient on transplant list urgently 1, 2, 3

Autoimmune Hepatitis

• Consider transjugular liver biopsy to establish diagnosis 1, 2, 3
• Initiate prednisone 40-60 mg/day 2, 3
• Place on transplant list even while administering corticosteroids 2, 3

Acute Fatty Liver of Pregnancy/HELLP Syndrome

Consult obstetrical services immediately and perform expeditious delivery, as recovery is typically rapid after delivery with supportive care only 2, 3

Wilson Disease

• Liver transplantation is uniformly required for survival 3
• Initiate albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange to acutely lower serum copper and limit hemolysis 3
• Do NOT use penicillamine due to risk of hypersensitivity 3

Drug-Induced Hepatotoxicity

• Discontinue all but essential medications immediately 3
• Obtain detailed medication history including prescription drugs, over-the-counter medications, herbs, and dietary supplements 3

Mushroom Poisoning

• Consider administration of penicillin G and silymarin 3
• List for transplantation immediately, as this is often the only lifesaving option 3

Encephalopathy Management

• Monitor mental status frequently and document using standardized grading system 1, 2
• Position patient with head elevated at 30 degrees and minimize stimulation 2
• Intubate for airway protection if Glasgow Coma Scale <8 or grade III-IV encephalopathy develops 1, 2
• Sedation: Use propofol due to favorable pharmacokinetics; avoid benzodiazepines as they worsen encephalopathy 1, 2
• Seizure control: Use phenytoin; add diazepam only as needed 2
• Avoid lactulose and rifaximin for ammonia reduction, as evidence for improved outcomes is limited 1

Coagulation Management

• Administer vitamin K to all patients 2, 3
• Reserve fresh frozen plasma (FFP) for active bleeding or invasive procedures only—prophylactic administration is not supported 2
• Most ALF patients have rebalanced hemostasis, and bleeding complications occur in only 10% 2
• Give platelets for counts <10,000/mm³ or before invasive procedures 2
• Consider recombinant activated factor VII for invasive procedures 2

Renal Support

• Avoid nephrotoxic agents including NSAIDs 1, 3
• If dialysis is needed, use continuous renal replacement therapy rather than intermittent hemodialysis 1, 2, 3

Infection Prevention

• Administer stress ulcer prophylaxis with H2 blockers or proton pump inhibitors 1, 2
• Screen aggressively for infections and treat early, as bacterial infections are common precipitants 2
• Consider empirical broad-spectrum antibiotics if worsening encephalopathy or signs of SIRS develop 1

Nutritional Support

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 1, 3
• Avoid severe protein restrictions 3
• If enteral feeding is contraindicated, use parenteral nutrition despite increased risk of fungal infection 3

Transplant Center Contact and Transfer

Contact a liver transplant center immediately upon diagnosis, as the transplantation window is often narrow. 1, 2, 3 Poor prognostic indicators requiring urgent listing include 2, 3:

• Idiosyncratic drug injury
• Non-hepatitis A viral infections
• Autoimmune hepatitis
• Mushroom poisoning
• Wilson disease
• Budd-Chiari syndrome
• Indeterminate cause

Post-transplant survival rates for ALF reach 80-90% even in patients with multiple organ failures 2, 3.

Common Pitfalls to Avoid

• Do NOT delay NAC administration while awaiting acetaminophen levels or detailed history 1, 2
• Do NOT use systemic corticosteroids for general ALF treatment except in confirmed autoimmune hepatitis 2
• Do NOT routinely correct coagulopathy with FFP unless active bleeding or invasive procedure planned 1, 2
• Do NOT use vasopressin for hemodynamic support 1, 2
• Do NOT use benzodiazepines for sedation as they worsen encephalopathy 1, 2
• Do NOT assume chronic liver disease is absent without hepatic Doppler ultrasound, as prognostic criteria do not apply to acute-on-chronic liver disease 1
• Do NOT delay transfer to transplant center while attempting to stabilize—early contact is essential 1, 2