What is the treatment approach for a patient with Acute Liver Failure (ALF)?

Treatment of Acute Liver Failure

All patients with acute liver failure require immediate ICU admission with continuous monitoring and early contact with a liver transplant center, as the transplantation window is often narrow and emergency liver transplantation may be life-saving. 1, 2

Immediate Critical Actions

ICU Admission and Monitoring

• Admit all ALF patients to an intensive care unit immediately with continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation 2, 3
• Contact a liver transplant center early in the evaluation process, as 5-10% of ALF cases require emergency transplantation 2, 3
• Transfer patients with Grade 3-4 hepatic encephalopathy to ICU immediately for airway protection 1, 3

Initial Diagnostic Workup

• Obtain immediately: acetaminophen level, prothrombin time/INR, comprehensive metabolic panel, arterial blood gases, lactate, complete blood count, toxicology screen, viral hepatitis serologies (IgM VHA, HBsAg, anti-HBc IgM) 1, 2
• For patients under age 40: add ceruloplasmin, 24-hour urine copper, and slit-lamp examination to evaluate for Wilson disease 2
• Perform hepatic Doppler ultrasound and echocardiography to assess vascular patency and cardiac function 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, 2
• Continue NAC even if >48 hours since acetaminophen ingestion 2
• Give activated charcoal (1 g/kg orally) if presentation within 4 hours of ingestion, administered just prior to NAC 2

Viral Hepatitis

• For suspected herpes simplex virus or varicella zoster: immediately place on transplant list and treat with acyclovir 1, 2
• Hepatitis A and B-related ALF: provide supportive care only, as no virus-specific treatment has proven effective 2

Autoimmune Hepatitis

• Obtain liver biopsy via transjugular approach to confirm diagnosis 1, 2
• Treat with prednisone 40-60 mg/day 2
• Place on transplant list even while administering corticosteroids 2
• Note: Systemic corticosteroids are ineffective for general ALF treatment except in autoimmune hepatitis 2, 3

Wilson Disease

• Wilson disease-related ALF is uniformly fatal without transplantation 2
• Initiate albumin dialysis, continuous hemofiltration, plasmapheresis, or plasma exchange to acutely lower serum copper and limit hemolysis 2
• Do NOT use penicillamine in ALF due to risk of hypersensitivity 2

Acute Fatty Liver of Pregnancy/HELLP Syndrome

• Consult obstetrical services immediately and perform expeditious delivery 1, 2
• Recovery is typically rapid after delivery with supportive care only 2

Ischemic Hepatitis ("Shock Liver")

• Cardiovascular support is the treatment of choice 1, 2
• Transplantation is seldom indicated 2

Budd-Chiari Syndrome

• Transplantation is indicated if significant liver failure is present 1, 2
• Exclude underlying malignancy before transplantation 1, 2

Drug-Induced Hepatotoxicity

• Discontinue all but essential medications immediately 2
• Obtain detailed medication history including prescription drugs, non-prescription medications, herbs, and dietary supplements 2

Mushroom Poisoning

• Consider administration of penicillin G and silymarin 2
• List for transplantation, as this is often the only lifesaving option 2

Supportive Care Management

Hemodynamic Support

• Maintain mean arterial pressure ≥50-60 mm Hg through aggressive fluid resuscitation first 2, 3
• Fluid resuscitation with colloid (albumin) is preferred over crystalloid 2
• All solutions should contain dextrose to maintain euglycemia 2
• If fluid replacement fails: use epinephrine, norepinephrine, or dopamine (NOT vasopressin) 1, 2
• Consider pulmonary artery catheterization in hemodynamically unstable patients 1

Hepatic Encephalopathy Management

• Monitor mental status frequently using West Haven criteria and Glasgow Coma Scale 1, 3
• Position patient with head elevated at 30 degrees and minimize stimulation 2
• For Grade 3-4 encephalopathy (Glasgow <8): intubate for airway protection 1, 2, 3
• Initiate aggressive lactulose: 25 mL every 1-2 hours until achieving 2-3 soft bowel movements, then titrate to maintain this frequency 3
• Consider adding rifaximin (400 mg three times daily or 550 mg twice daily) as adjunctive therapy 3
• L-ornithine-L-aspartate (LOLA) 30 g/day IV can be considered for refractory hyperammonemia 3
• Control seizures with phenytoin; avoid benzodiazepines when possible 2
• Use propofol for sedation due to favorable pharmacokinetics; avoid dexmedetomidine due to exclusive hepatic metabolism 1, 2

Intracranial Pressure Management

• Do NOT use empiric treatments to reduce ICP 1
• Maintain serum sodium at 140-145 mmol/L 1, 2
• Infusion of hypertonic saline can significantly decrease intracranial pressure if needed 2
• Transcranial Doppler ultrasound is useful for monitoring; ICP devices have been associated with hemorrhagic complications (7-20% of cases) 1
• Avoid high PEEP (>10 cmH₂O) due to risk of hepatic congestion 1, 2

Coagulation Management

• Administer vitamin K to all ALF patients 2
• Reserve fresh frozen plasma and coagulation factors for active bleeding or invasive procedures only 1, 2
• Most ALF patients have rebalanced hemostasis; bleeding complications occur in only 10% of patients 1, 2
• Give platelets for counts <10,000/mm³ or before invasive procedures 2
• Recombinant activated factor VII may be considered for invasive procedures 2

Renal Support

• Avoid nephrotoxic agents including non-steroidal anti-inflammatory drugs 1, 2
• If dialysis is needed: use continuous renal replacement therapy rather than intermittent hemodialysis 1, 2
• Early commencement of CRRT to control hyperammonemia is now considered an important standard of care 4
• Monitor regional citrate anticoagulation due to potential metabolic effects in ALF 1

Metabolic Management

• Monitor blood glucose at least every 2 hours 1, 2
• Manage hypoglycemia with continuous glucose infusions 2
• Monitor and aggressively correct electrolytes: magnesium, phosphate, and potassium require repeated supplementation 2, 3
• Liberal supplementation is recommended in first two weeks, particularly with acute kidney injury present 3

Nutritional Support

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 2
• Start via nasogastric/nasojejunal tube if patient cannot maintain adequate oral intake 3
• Severe protein restrictions should be avoided 2
• Standard enteral formulas are appropriate; no evidence supports disease-specific formulations 3
• If enteral feedings are contraindicated, parenteral nutrition is an option despite risks of fungal infection 2

Infection Prevention and Management

• Start empirical broad-spectrum antibiotics immediately if signs of sepsis and/or worsening encephalopathy 2, 5, 3
• Bacterial infections occur in 60-80% of ALF patients 5, 3
• Recommended regimen: Third-generation cephalosporin (ceftriaxone or cefotaxime) OR piperacillin-tazobactam 5, 3
• Screen aggressively for infections and treat early 2
• Provide prophylaxis for stress ulceration with H2 blockers or proton pump inhibitors 1, 2

Respiratory Support

• Provide oxygen therapy and mechanical ventilation if respiratory failure develops 2
• Use standard lung protective ventilator strategy per critical care guidelines 1, 2

Liver Transplantation

Indications and Timing

• Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death 2
• List patients early in the course of ALF, particularly those suitable for transplant 2
• Post-transplant survival rates reach 80-90% even in patients with multiple organ failures 2

Prognostic Tools

• Use MELD score rather than King's College Criteria as a prognostic scoring system 1
• A MELD score of 30.5 (fixed cut-off level) should be used for prognosis; higher scores predict need for liver transplantation 1
• King's College criteria remain useful but have limited sensitivity (50-60%) 2

Poor Prognostic Indicators

• Idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, and indeterminate cause 2

Extracorporeal Support Systems

Current Evidence

• Extracorporeal artificial liver support systems should only be used within the context of a clinical trial 1
• Various liver support systems have been tested with no certain evidence of efficacy 2
• Plasma exchange may have a role in the sickest ALF patients 4
• Sorbent systems may show transient improvement of hepatic encephalopathy but no improvement in hepatic function or long-term benefit 2

Common Pitfalls to Avoid

• Do NOT delay lactulose waiting for ammonia results; treat based on clinical presentation 3
• Do NOT use rifaximin alone to lower ammonia in ALF; it is not recommended as monotherapy 1, 3
• Do NOT routinely correct coagulation; restrict clotting factors administration unless active bleeding 1
• Do NOT use benzodiazepines or psychotropic drugs (such as metoclopramide) as they worsen encephalopathy 1
• Do NOT use treatments (lactulose, rifaximin) to lower ammonia levels without clinical indication 1
• Avoid over-aggressive lactulose causing dehydration, hypernatremia, or aspiration 3
• Monitor for ileus: If present, hold oral lactulose and use rectal route 3

Indeterminate Etiology

• If etiology remains elusive after extensive initial evaluation, liver biopsy via transjugular approach may be appropriate to identify specific etiology that might influence treatment strategy 1, 2
• Consider underlying malignancy in patients with previous cancer history or massive hepatomegaly; obtain imaging and liver biopsy to confirm or exclude diagnosis 1