What is the complete management of acute fulminant hepatic failure?

Complete Management of Acute Fulminant Hepatic Failure

Immediate ICU admission with continuous multi-organ monitoring and early transplant center contact are mandatory, as survival depends on rapid prognostic assessment, etiology-specific interventions (particularly N-acetylcysteine for acetaminophen), aggressive supportive care targeting cerebral edema and hemodynamic stability, and timely liver transplantation when King's College criteria predict mortality. 1

Immediate Actions and ICU Admission

• Admit all patients to an intensive care unit immediately when acute liver failure is diagnosed (INR ≥1.5 plus any degree of encephalopathy), as clinical deterioration occurs hour-by-hour 1
• Contact a liver transplant center within the first hours of diagnosis, as the "transplantation window" is narrow and early listing improves outcomes 1, 2
• Establish continuous monitoring of hepatic, renal, neurologic, pulmonary, coagulation, and hemodynamic parameters to detect organ failure early 1, 2

Etiology-Specific Treatments (First Priority)

Acetaminophen Toxicity

• Administer N-acetylcysteine immediately: 140 mg/kg orally or via nasogastric tube, followed by 70 mg/kg every 4 hours for 17 doses 1
• Continue N-acetylcysteine even if >48 hours have elapsed since ingestion 1
• Give activated charcoal (1 g/kg orally) only if presentation is within 4 hours of ingestion, administered just prior to NAC 1

Viral Hepatitis

• Hepatitis A and B require supportive care only, as no virus-specific treatment has proven effective 1
• For herpes simplex virus or varicella zoster: immediately list for transplantation and treat with acyclovir 1
• Administer nucleoside analogs to hepatitis B patients requiring chemotherapy or immunosuppression, continuing for 6 months after treatment completion 1

Wilson Disease

• Wilson disease-related acute liver failure is uniformly fatal without transplantation 1
• Initiate albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange immediately to lower serum copper and limit hemolysis 1
• Do not use penicillamine due to hypersensitivity risk 1

Autoimmune Hepatitis

• Obtain transjugular liver biopsy to confirm diagnosis (safer in coagulopathic patients) 1
• Treat with prednisone 40-60 mg/day 1
• List for transplantation even while administering corticosteroids, as medical therapy alone is often insufficient 1

Pregnancy-Related (HELLP/Acute Fatty Liver of Pregnancy)

• Expeditious delivery with obstetrical consultation is the definitive treatment 1
• Recovery is typically rapid after delivery with supportive care only 1

Ischemic ("Shock Liver")

• Cardiovascular support with aggressive hemodynamic management is the treatment of choice 3
• Transplantation is seldom indicated for purely ischemic injury 3

Mushroom Poisoning

• Administer penicillin G and silymarin 1
• List for transplantation immediately, as this is often the only lifesaving option 1

Drug-Induced Hepatotoxicity

• Discontinue all non-essential medications immediately 1
• Obtain detailed medication history including prescription drugs, over-the-counter medications, herbs, and dietary supplements 1

Hemodynamic Management

• Maintain mean arterial pressure ≥50-60 mmHg through aggressive fluid resuscitation first 1, 3
• Prefer colloid (albumin) over crystalloid (saline) for fluid resuscitation; all solutions should contain dextrose to maintain euglycemia 1
• Consider pulmonary artery catheterization in hemodynamically unstable patients to guide therapy 1
• If fluid replacement fails to maintain MAP, use epinephrine, norepinephrine, or dopamine (but NOT vasopressin) 1, 3
• Dopamine is associated with increased systemic oxygen delivery in acute liver failure 1

Neurological Management

Encephalopathy Monitoring and Positioning

• Monitor mental status frequently and transfer to ICU if level of consciousness declines 1
• Position patient with head elevated at 30 degrees and minimize stimulation 1

Airway Protection

• Intubate for grades III-IV encephalopathy to protect the airway 1

Sedation

• Use propofol for sedation due to favorable pharmacokinetics 1
• Avoid benzodiazepines as they worsen encephalopathy 1

Seizure Control

• Control seizures with phenytoin, adding diazepam only as needed 1

Cerebral Edema Prevention

• Maintain serum sodium at 140-145 mmol/L; infusion of hypertonic saline can significantly decrease intracranial pressure 1
• Consider lactulose to reduce ammonia levels, though evidence for improved outcomes is limited 1

Coagulation Management

• Do NOT correct INR prophylactically with fresh frozen plasma or coagulation factors unless there is active bleeding or an invasive procedure is planned 1
• Most acute liver failure patients have rebalanced hemostasis between pro- and anticoagulant factors; bleeding complications occur in only 10% 1
• Administer vitamin K to all patients 1
• Give platelets for counts <10,000/mm³ or before invasive procedures 1
• Consider recombinant activated factor VII for invasive procedures 1

Renal Management

• Avoid all nephrotoxic agents including NSAIDs 1
• If dialysis is needed, use continuous renal replacement therapy rather than intermittent hemodialysis 1, 2
• Monitor regional citrate anticoagulation carefully due to potential metabolic effects in acute liver failure 1
• For hepatorenal syndrome, treat with terlipressin and albumin (or norepinephrine if terlipressin unavailable) 1

Metabolic Management

• Monitor blood glucose at least every 2 hours and manage hypoglycemia with continuous glucose infusions 1
• Monitor and supplement phosphate, magnesium, and potassium levels as needed 1
• Maintain serum sodium at 140-145 mmol/L 1

Nutritional Support

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 1
• Avoid severe protein restrictions 1
• Branched-chain amino acids have not been shown superior to other enteral preparations 1
• If enteral feedings are contraindicated, use parenteral nutrition despite risks of fungal infection 1

Respiratory Management

• Provide oxygen therapy and mechanical ventilation if respiratory failure develops 1
• Use protective ventilation settings per critical care guidelines 1
• Avoid high PEEP (>10 cmH₂O) due to risk of hepatic congestion 1

Infection Prevention and Management

• Screen aggressively for infections and treat early, as bacterial infections are common precipitants 1
• Administer prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors 1
• H2 blockers (ranitidine) have proven effectiveness; proton pump inhibitors may provide superior protection 1
• Sucralfate is acceptable as second-line treatment 1

Prognostic Assessment and Transplant Listing

King's College Criteria (Best Validated Tool)

For Acetaminophen-Induced Acute Liver Failure:

• Poor prognosis if arterial pH <7.3 after resuscitation **OR** all three of: INR >6.5, creatinine >300 µmol/L, and grade 3-4 encephalopathy 1

For Non-Acetaminophen Acute Liver Failure:

• Poor prognosis if INR >6.5 OR any three of: age <10 or >40 years, non-A/non-B hepatitis, drug-induced injury, jaundice >7 days before encephalopathy, INR >3.5, bilirubin >300 µmol/L 1

Additional Poor Prognostic Indicators

• Serum ammonia >100-150 µmol/L predicts increased risk of intracranial hypertension 1
• Factor V activity <20% (Clichy-Villejuif criteria) indicates poor outcome 1
• Requirement for vasopressor support is an independent predictor of mortality 1
• Grade 3-4 encephalopathy is associated with only ~33% short-term survival without transplantation 1
• Poor prognostic etiologies include idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, and indeterminate cause 1

Transplant Decision-Making

• List urgently for transplantation when prognostic indicators suggest high likelihood of death 1
• Post-transplant survival rates reach 80-90% even in patients with multiple organ failures 1, 2
• Early transplant provides 78% one-year survival compared to <10% in those not transplanted 2
• Rapid decision-making by a multidisciplinary team is necessary because the transplantation window is narrow 2
• Prognosis assessment is more accurate when performed with SOFA score a few days after ICU admission rather than on admission 2

Artificial Liver Support Systems

• MARS and Prometheus systems do not demonstrate survival benefit at 28 and 90 days in randomized controlled trials 2, 4
• Post-hoc analysis shows significant improvement in hepatic encephalopathy and hepatorenal syndrome with MARS 2
• Observational studies suggest artificial liver support may improve short-term survival (14-day and 28-day) in patients with multiple organ failure, potentially serving as a bridge to transplantation 2, 4
• Refer patients to expert centers early after decompensation if considering artificial liver support 2, 4

Critical Pitfalls to Avoid

• Do not delay transplant center contact—early referral is essential 1
• Do not routinely correct INR with plasma products in the absence of bleeding, as this obscures prognostic assessment 1
• Do not use vasopressin for hemodynamic support 1
• Do not restrict protein severely in nutritional support 1
• Do not use intermittent hemodialysis when continuous renal replacement therapy is available 1
• Do not delay empirical antibiotics while awaiting culture results 3
• Acetaminophen toxicity may occur without clear ingestion history—always measure serum acetaminophen level 1
• Consider Wilson disease in all patients ≤40 years without obvious cause 1
• Pregnancy-related acute liver failure requires obstetric delivery, not immediate transplantation 1