What is the management approach for a patient with acute liver failure?

Acute Liver Failure Management

Immediate Actions and ICU Admission

All patients with acute liver failure (ALF) must be admitted to an intensive care unit with continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation, and immediate contact with a liver transplant center should be initiated as the "transplantation window" is often narrow. 1

• ALF is defined by coagulopathy (INR ≥1.5) and any degree of altered mental status in patients without preexisting cirrhosis, with illness duration ≤26 weeks 1
• Hospital admission is mandatory when prothrombin time is prolonged by 4-6 seconds or more (INR ≥1.5) with any evidence of altered sensorium 1

Initial Laboratory Evaluation

Obtain immediately upon presentation:

• Prothrombin time/INR, comprehensive metabolic panel, arterial blood gases, lactate 1
• Complete blood count, acetaminophen level, toxicology screen 1
• Viral hepatitis serologies (HAV IgM, HBsAg, anti-HBc IgM, anti-HCV, HCV RNA) 1
• If age <40 years: ceruloplasmin, 24-hour urine copper, slit-lamp examination for Wilson disease 1
• Autoimmune markers (ANA, ASMA, IgG) if suspected 1

Etiology-Specific Treatments

Acetaminophen Toxicity

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

Autoimmune Hepatitis

• Obtain transjugular liver biopsy to confirm diagnosis 1
• Treat with prednisone 40-60 mg/day 1
• List for transplantation immediately even while administering corticosteroids 1

Herpes Simplex Virus/Varicella Zoster

• Immediately place on transplant list and treat with acyclovir 1

Wilson Disease

• Uniformly fatal without transplantation 1
• Initiate albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange to acutely lower serum copper and limit hemolysis 1
• Do NOT use penicillamine due to hypersensitivity risk 1

Acute Fatty Liver of Pregnancy/HELLP Syndrome

• Consult obstetrical services and perform expeditious delivery 1
• Recovery is typically rapid after delivery with supportive care only 1

Mushroom Poisoning

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

Drug-Induced Hepatotoxicity

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

Ischemic Hepatitis ("Shock Liver")

• Cardiovascular support is the treatment of choice 1
• Transplantation seldom indicated 1

Budd-Chiari Syndrome

• Transplantation indicated if significant liver failure present 1
• Exclude underlying malignancy before transplantation 1

Viral Hepatitis A and B

• Treat with supportive care only as no virus-specific treatment has been proven effective 1

Hemodynamic Management

• Maintain mean arterial pressure ≥50-60 mm Hg through aggressive fluid resuscitation first 1
• Use colloid (albumin) preferentially over crystalloid (saline), with all solutions containing dextrose to maintain euglycemia 1
• If fluid replacement fails to maintain MAP, use vasopressors: epinephrine, norepinephrine, or dopamine (NOT vasopressin) 1
• Consider pulmonary artery catheterization in hemodynamically unstable patients 2

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 for airway protection 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 Management

• Maintain serum sodium at 140-145 mmol/L 1
• Infusion of hypertonic saline can significantly decrease intracranial pressure 1

Ammonia Reduction

• Consider lactulose to reduce ammonia levels, though evidence for improved outcomes is limited 1

Coagulation Management

• Administer vitamin K to all patients 1
• Reserve fresh frozen plasma (FFP) for invasive procedures or active bleeding only 1
• Most ALF patients have rebalanced hemostasis between pro- and anticoagulant factors, and bleeding complications occur in only 10% of patients 1
• Give platelets for counts <10,000/mm³ or before invasive procedures 1
• Consider recombinant activated factor VII for invasive procedures 1

Renal Support

• Avoid nephrotoxic agents 1
• If dialysis is needed, use continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis 1
• Monitor regional citrate anticoagulation carefully due to potential metabolic effects in ALF 1

Metabolic Management

• Monitor blood glucose at least every 2 hours 1
• Manage hypoglycemia with continuous glucose infusions 1
• Monitor and supplement phosphate, magnesium, and potassium levels as needed 1

Nutritional Support

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 1
• Severe protein restrictions should be avoided 1
• Branched-chain amino acids have not been shown superior to other enteral preparations 1
• If enteral feedings are contraindicated, parenteral nutrition is an option despite risks of fungal infection 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 such as ranitidine have proven effectiveness, and proton pump inhibitors may provide superior protection 1

Liver Transplantation

Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death, with post-transplant survival rates reaching 80-90% even in patients with multiple organ failures. 1

Poor Prognostic Indicators

• Idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, and indeterminate cause 1

Prognostic Tools

• King's College criteria remain the best prognostic tool, though sensitivity is limited (50-60%) 1

Timing

• List patients early in the course of ALF, particularly those suitable for transplant 1
• Contact transplant center early as 10% of listed patients die on the waiting list despite UNOS status 1 priority 1

Liver Support Systems

• Various liver support systems have been tested with no certain evidence of efficacy 1
• Sorbent systems may show transient improvement of hepatic encephalopathy but no improvement in hepatic function or long-term benefit 1
• Recent studies show improved short-term survival for some patients treated with porcine hepatocyte-based bioartificial liver, but further research is needed 1
• Plasmapheresis may stabilize patients and delay, though not eliminate, the need for transplantation 1

Common Pitfalls

• Do NOT use systemic corticosteroids for general ALF treatment (except in autoimmune hepatitis) 1
• Do NOT use vasopressin as a vasopressor 1
• Do NOT restrict protein severely despite encephalopathy 1
• Do NOT give prophylactic FFP or coagulation factors without active bleeding or planned procedures 1
• Consider malignant infiltration in patients with previous cancer history or massive hepatomegaly 1
• If etiology remains unclear after extensive evaluation, transjugular liver biopsy may identify specific etiology that influences treatment 1