What is the management of liver failure?

Management of Liver Failure

Immediate Critical Care and ICU Admission

All patients with acute liver failure (ALF) must be admitted to an intensive care unit immediately with continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation, and early contact with a liver transplant center should be initiated without delay. 1

• Transfer to ICU is mandatory when prothrombin time is prolonged by 4-6 seconds or more (INR ≥1.5) and there is any evidence of altered sensorium 1
• The "transplantation window" is often narrow, requiring immediate transplant center contact early in the evaluation process 1
• Post-transplant survival rates reach 80-90% even in patients with multiple organ failures 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 acetaminophen ingestion 1
• Activated charcoal (1 g/kg orally) if presentation within 4 hours of ingestion, given just prior to NAC 1

Autoimmune Hepatitis

• Consider transjugular liver biopsy to establish diagnosis 1
• Treat with corticosteroids (prednisone 40-60 mg/day) 1
• Place patients on transplant list even while administering corticosteroids 1

Viral Hepatitis

• Hepatitis A and B-related ALF: supportive care only, as no virus-specific treatment has proven effective 1
• Herpes virus or varicella zoster: immediately place on transplant list and treat with acyclovir 1

Wilson Disease

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

Acute Fatty Liver of Pregnancy/HELLP Syndrome

• Consultation with obstetrical services and expeditious delivery are required 1
• Recovery is typically rapid after delivery with supportive care only 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

Mushroom Poisoning

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

Ischemic Hepatitis ("Shock Liver")

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

Hemodynamic Management

• Maintain mean arterial pressure ≥50-60 mm Hg through aggressive fluid resuscitation first 1
• Fluid resuscitation with colloid (albumin) is preferred over crystalloid (saline); all solutions should contain dextrose to maintain euglycemia 2, 1
• Consider pulmonary artery catheterization in hemodynamically unstable patients 1
• If fluid replacement fails to maintain adequate MAP, use vasopressors: epinephrine, norepinephrine, or dopamine (NOT vasopressin) 1
• Dopamine is associated with increased systemic oxygen delivery in ALF 1

Central Nervous System and Encephalopathy Management

• Monitor mental status frequently; transfer to ICU if level of consciousness declines 1
• Position patient with head elevated at 30 degrees and minimize stimulation 1
• For grades III-IV encephalopathy, intubation is recommended for airway protection 1
• Control seizures with phenytoin; avoid benzodiazepines when possible 1
• Use propofol for sedation due to favorable pharmacokinetics; avoid dexmedetomidine due to exclusive hepatic metabolism 1
• Maintain serum sodium at 140-145 mmol/L; infusion of hypertonic saline can significantly decrease intracranial pressure 1
• Lactulose may be considered to reduce ammonia levels, though evidence for improved outcomes is limited 1, 3

Coagulation Management

• Administer vitamin K to all patients with ALF 1
• Reserve fresh frozen plasma (FFP) for invasive procedures or active bleeding only; prophylactic administration is not supported 1
• Most ALF patients have rebalanced hemostasis between pro- and anticoagulant factors; bleeding complications occur in only 10% of patients 1
• Give platelets for counts <10,000/mm³ or before invasive procedures 1
• Recombinant activated factor VII may be considered for invasive procedures 1

Gastrointestinal Bleeding Prophylaxis

Patients with ALF in the ICU should receive prophylaxis with H2 blocking agents or proton pump inhibitors (or sucralfate as a second-line agent) for acid-related gastrointestinal bleeding associated with stress. 2

• H2 blockers (such as ranitidine) have proven effectiveness in preventing GI bleeding 2
• PPIs are almost certainly effective and may provide superior protection, though this remains to be proven 2
• Sucralfate may be acceptable as second-line treatment 2

Renal Support

• Avoid nephrotoxic agents 1
• If dialysis support is needed for acute renal failure, use continuous modes (continuous renal replacement therapy) rather than intermittent hemodialysis 2, 1
• Regional citrate anticoagulation should be monitored due to potential metabolic effects in ALF 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; liberal supplementation recommended in first two weeks 1, 4
• 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
• 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

Bacterial infections occur in 60-80% of acute liver failure patients, making aggressive infection screening and early treatment essential. 1, 5

• Start empirical broad-spectrum antibiotics immediately if signs of sepsis and/or worsening encephalopathy 5
• Recommended regimen: third-generation cephalosporin (ceftriaxone or cefotaxime) OR piperacillin-tazobactam 4, 5
• Screen aggressively for infections and treat early, as bacterial infections are common precipitants 1
• Prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors is recommended 1

Respiratory Support

• 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

Liver Transplantation

Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death. 1

• List patients early in the course of ALF, particularly those suitable for transplant 1
• Post-transplant survival rates reach 80-90% 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
• King's College criteria remain the best prognostic tool, though sensitivity is limited (50-60%) 1
• For ACLF-3 with organ failures ≥4 or CLIF-C ACLFs >64 at days 3-7, discontinue intensive support if transplant is contraindicated or unavailable due to futility 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 with ALF treated with porcine hepatocyte-based bioartificial liver, but further research is needed 1
• Plasmapheresis may stabilize patients and serve as bridging therapy until liver transplantation, particularly in Wilson disease to protect kidneys from copper-mediated tubular damage 1

Common Pitfalls to Avoid

• Do not delay ICU admission or transplant center contact 1
• Avoid prophylactic administration of coagulation factors; reserve for active bleeding or procedures 1
• Do not use systemic corticosteroids for general ALF treatment except in autoimmune hepatitis 1
• Avoid benzodiazepines as they worsen encephalopathy 1
• Do not use vasopressin for hemodynamic support 1
• Avoid high PEEP ventilation settings 1
• Changes in aminotransferase levels correlate poorly with prognosis; do not rely on these for prognostication 1