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

Management of Acute Liver Failure

Immediate Actions and ICU Admission

All patients with acute liver failure (ALF) require immediate ICU admission with continuous monitoring of liver, kidney, brain, lung, coagulation, and circulation, and early contact with a liver transplant center should be initiated immediately. 1, 2

• Transfer patients to a liver transplant center as soon as possible, as the "transplantation window" is often narrow and transplant-free survival rates are highest at specialized centers 1, 3
• ALF is defined by coagulopathy (INR ≥1.5) and any degree of encephalopathy in patients without pre-existing liver disease, with illness duration ≤26 weeks 1

Initial Diagnostic Workup

Obtain the following laboratory tests immediately to guide etiology-specific treatment 1, 4:

• Acetaminophen level (even if patient denies ingestion)
• PT/INR, factor V
• Comprehensive metabolic panel including glucose, electrolytes, creatinine
• Arterial blood gas, lactate, ammonia
• Complete blood count, ferritin
• Hepatitis A, B, C serology
• Toxicology screen (amphetamines, cocaine)
• If age <40 years: ceruloplasmin, 24-hour urine copper, slit-lamp examination for Wilson disease 1, 2
• Autoimmune markers (ANA, ASMA, IgG) if suspected 1

Imaging studies 1, 4:

• Doppler ultrasound of liver to exclude chronic disease and verify vessel patency
• Echocardiography if suspected cardiac ischemia, heart failure, or when AST exceeds ALT

Etiology-Specific Treatments

Acetaminophen Toxicity

Administer N-acetylcysteine (NAC) immediately for all suspected acetaminophen cases, even if >48 hours since ingestion. 1, 5

• Loading dose: 150 mg/kg IV over 60 minutes (preferred over 15-minute infusion to reduce hypersensitivity reactions) 1
• Second dose: 50 mg/kg IV over 4 hours 1
• Third dose: 100 mg/kg IV over 16 hours 1
• Alternative oral dosing: 140 mg/kg by mouth/NG tube, then 70 mg/kg every 4 hours for 17 doses 1, 5
• If presentation within 4 hours: give activated charcoal 1 g/kg orally just prior to NAC 1

Critical point: NAC should be administered to ALL patients with ALF regardless of etiology, not just acetaminophen cases, as it improves outcomes across all causes 1, 4

Viral Hepatitis

• Herpes simplex or varicella zoster: Administer acyclovir immediately if suspected and list for transplantation urgently 1, 2
• Hepatitis A and B: Supportive care only; no virus-specific treatment proven effective 2
• For hepatitis B patients requiring chemotherapy/immunosuppression: nucleoside analogs for 6 months after treatment completion 2

Autoimmune Hepatitis

• Consider transjugular liver biopsy for diagnosis confirmation 1, 2
• Prednisone 40-60 mg/day 1, 2
• List for transplantation even while administering corticosteroids 1, 2

Wilson Disease

• Uniformly fatal without transplantation - list immediately 2
• Acutely lower serum copper with plasmapheresis, albumin dialysis (MARS), continuous hemofiltration, or plasma exchange 2
• Do NOT use penicillamine due to hypersensitivity risk 2

Pregnancy-Related (Acute Fatty Liver/HELLP)

• Consult obstetrics immediately and deliver promptly 1, 2
• Recovery typically rapid after delivery with supportive care only 1, 2

Drug-Induced Hepatotoxicity

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

Mushroom Poisoning

• Consider penicillin G and silymarin 2
• List for transplantation immediately as often the only lifesaving option 2

Ischemic Hepatitis ("Shock Liver")

• Cardiovascular support is primary treatment 1
• Transplantation seldom indicated unless significant liver failure persists 1

Budd-Chiari Syndrome

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

Neurological Management

Hepatic Encephalopathy Monitoring

• Monitor mental status frequently; transfer to ICU if consciousness declines 1, 4
• Position head elevated at 30 degrees and minimize stimulation 1
• Intubate for airway protection if Glasgow Coma Scale <8 or grade III-IV encephalopathy 1, 4

Sedation

• Use propofol for sedation due to favorable pharmacokinetics 1, 4
• Avoid benzodiazepines as they worsen encephalopathy 1, 4
• Minimize sedation depth 4

Cerebral Edema Management

• Maintain serum sodium 140-145 mmol/L 1, 4
• Hypertonic saline infusion can significantly decrease intracranial pressure 1
• Control seizures with phenytoin; add diazepam only as needed 1
• Consider lactulose to reduce ammonia levels, though evidence for improved outcomes is limited 1

Ammonia Control

Early initiation of continuous renal replacement therapy (CRRT) to control hyperammonemia is now considered standard of care. 3

Hemodynamic Management

• Maintain mean arterial pressure ≥50-60 mmHg 1, 2, 4
• Aggressive fluid resuscitation first; colloid (albumin) preferred over crystalloid 1
• All solutions should contain dextrose to maintain euglycemia 1
• If fluid replacement fails, use vasopressors: epinephrine, norepinephrine, or dopamine (NOT vasopressin) 1, 2, 4
• Consider pulmonary artery catheterization in hemodynamically unstable patients 2, 4

Respiratory Management

• Provide oxygen therapy and mechanical ventilation if respiratory failure develops 1
• Use protective ventilation strategies per critical care guidelines 1, 4
• Avoid high PEEP (>10 cmH₂O) due to risk of hepatic congestion 1

Renal Management

• Avoid nephrotoxic agents including NSAIDs 1, 4
• If dialysis needed, use continuous renal replacement therapy (CRRT) rather than intermittent hemodialysis 1, 2, 4
• Monitor regional citrate anticoagulation carefully due to potential metabolic effects in ALF 1
• For hepatorenal syndrome: treat with terlipressin and albumin (or norepinephrine if terlipressin unavailable) 1

Coagulation Management

Most ALF patients have rebalanced hemostasis between pro- and anticoagulant factors; bleeding complications occur in only 10% of patients. 1

• Administer vitamin K to all patients 1
• Reserve fresh frozen plasma (FFP) for active bleeding or invasive procedures only 1, 4
• Prophylactic administration of coagulation factors is not supported 1
• Give platelets for counts <10,000/mm³ or before invasive procedures 1
• Consider recombinant activated factor VII for invasive procedures 1

Metabolic Management

• Monitor blood glucose at least every 2 hours 1, 4
• Manage hypoglycemia with continuous glucose infusions 1, 2
• Monitor and supplement phosphate, magnesium, and potassium as needed 1, 2

Nutritional Support

• Initiate enteral feedings early with moderate protein intake (approximately 60 grams per day) 1, 2
• Severe protein restrictions should be avoided 1
• Branched-chain amino acids have not been shown superior to other enteral preparations 1
• If enteral feedings contraindicated, parenteral nutrition is an option despite risks of fungal infection 2

Infection Prevention and Management

• Screen aggressively for infections and treat early, as bacterial infections are common precipitants 1
• Administer empirical broad-spectrum antibiotics to patients with worsening hepatic encephalopathy or signs of SIRS 4
• Provide stress ulcer prophylaxis with H2 blockers or proton pump inhibitors 1, 4
• Sucralfate may be acceptable as second-line treatment 1

Liver Support Systems

Therapeutic plasma exchange may have a role in the sickest ALF patients and should be considered as bridging therapy until transplantation. 3, 6

• Various other liver support systems (MARS, sorbent systems) have been tested without definitive evidence of efficacy 1, 2
• Sorbent systems may show transient improvement of hepatic encephalopathy but no improvement in hepatic function or long-term benefit 2
• Porcine hepatocyte-based bioartificial liver has shown improved short-term survival in some studies but requires further research 2

Liver Transplantation

Urgent hepatic transplantation is indicated when prognostic indicators suggest high likelihood of death, with post-transplant survival rates of 80-90%. 1, 2, 4

King's College Criteria for Transplantation

Acetaminophen-induced ALF 1:

• Arterial pH <7.3 after adequate volume resuscitation, OR
• PT >100 seconds with serum creatinine >3.4 mg/dL in patients with grade III/IV coma

Non-acetaminophen ALF 1:

• PT >100 seconds irrespective of coma grade

Poor Prognostic Indicators Warranting Early Listing 2, 4:

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

Important Caveats

• King's College criteria have limited sensitivity (50-60%) but remain the best prognostic tool 1
• List patients early in the course of ALF, particularly those suitable for transplant 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

Common Pitfalls to Avoid

• Do NOT withhold NAC based on time since ingestion or etiology - give to all ALF patients 1, 4
• Do NOT use systemic corticosteroids for general ALF treatment except in autoimmune hepatitis 1
• Do NOT routinely correct coagulation abnormalities unless active bleeding or invasive procedure planned 1, 4
• Do NOT delay transplant center contact - the window for transplantation is narrow 1
• Do NOT use vasopressin for hemodynamic support 1, 2
• Do NOT use intermittent hemodialysis - CRRT is preferred 1, 2, 4
• Do NOT restrict protein severely - moderate intake (60g/day) is recommended 1, 2
• Consider malignant infiltration of liver in patients with previous cancer history or massive hepatomegaly, as it can mimic ALF 1