What are the guidelines for management of acute liver failure?

Management of Acute Liver Failure

Immediate Diagnostic Evaluation

All patients with suspected acute liver failure require immediate laboratory assessment including serum acetaminophen levels (regardless of history), hepatitis A and B serologies, urinary toxin screen, and coagulation parameters to identify treatable causes and guide prognosis. 1

• Obtain detailed medication history including all prescription drugs, over-the-counter medications, herbal supplements, and dietary products taken within the past year, with specific attention to timing, dosage, and duration of use 2
• Perform hepatic Doppler ultrasound to exclude chronic liver disease, verify vessel patency, and rule out Budd-Chiari syndrome 1, 3
• Conduct echocardiography when ischemic hepatocellular injury is suspected (cardiac failure, arrhythmias, or AST exceeding ALT) to assess cardiac function 1, 3
• Monitor arterial blood gases, lactate levels, and arterial ammonia to assess disease severity and guide management 1, 3
• Consider transjugular liver biopsy only when autoimmune hepatitis is strongly suspected, as routine liver biopsy is not recommended due to bleeding risk and limited impact on management 2, 1

Additional Testing Based on Clinical Context

• Test for varicella zoster virus (VZV) in immunocompromised patients or those with compatible clinical features, though routine testing in immunocompetent patients is not recommended 2
• Test for hepatitis E virus (HEV) in pregnant women presenting with ALF, as this population has significantly elevated mortality (56% range 33-71%) 2, 1
• Perform autoantibody testing for autoimmune hepatitis, as 93% of AIH patients have positive autoantibodies and corticosteroid treatment may improve outcomes 2, 1

Etiology-Specific Management

Acetaminophen Toxicity

N-acetylcysteine must be administered immediately in all patients with acetaminophen-associated ALF regardless of time since ingestion. 2, 4

• Administer loading dose of 150 mg/kg IV over 1 hour, followed by maintenance dosing: 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours (total 300 mg/kg over 21 hours) 4
• Use the Rumack-Matthew nomogram for patients with known time of ingestion occurring more than 4 hours prior; if acetaminophen level is at or above the "possible toxicity line," continue full NAC course 4
• For indeterminate cases or unknown ingestion time, administer NAC empirically as indeterminate ALF may represent unrecognized acetaminophen toxicity 2, 3
• Consider extended NAC therapy beyond 21 hours if acetaminophen levels remain detectable, ALT/AST continue rising, or INR remains elevated after completing the standard protocol 4

Non-Acetaminophen Causes

• Administer acyclovir immediately (10 mg/kg IV every 8 hours) for suspected or documented herpes simplex virus or varicella zoster hepatitis, even before confirmatory testing, as skin lesions are present in only 50% of cases 2, 1
• Consider penicillin G and silymarin (30-40 mg/kg/day for 3-4 days) in patients with known or suspected mushroom poisoning, and list immediately for transplantation 2
• Initiate corticosteroids for autoimmune hepatitis while simultaneously listing for transplantation, as treatment does not preclude need for transplant 1
• Consider lamivudine or adefovir for acute hepatitis B, though controlled trial data are lacking 2
• Arrange expeditious delivery in pregnant patients with acute fatty liver of pregnancy or HELLP syndrome in consultation with obstetrics 1
• Discontinue all non-essential medications immediately in suspected drug-induced hepatotoxicity 2

N-Acetylcysteine in Non-Acetaminophen ALF

For non-acetaminophen-associated ALF, N-acetylcysteine should only be used within clinical trials, though systematic administration may be considered given marginal mortality benefit and minimal toxicity. 2

• Post-hoc analysis showed mortality benefit specifically in patients with stage 1 or 2 hepatic encephalopathy 2
• Combined RCT data showed marginally significant mortality benefit (RR 0.65,95% CI 0.43-0.99) with relatively minor toxicity 2
• Recent observational data suggest increased use (15.8% to 49.4%) correlates with improved outcomes 5

Critical Care Management

Neurological Management

Maintain serum sodium between 140-145 mmol/L and monitor hepatic encephalopathy frequently using standardized scales to prevent cerebral edema. 1, 3

• Monitor blood glucose at least every 2 hours and maintain euglycemia with continuous glucose infusions (target 60g protein/day), as hypoglycemia symptoms are obscured by encephalopathy 2, 1, 3
• Perform tracheal intubation and sedation for progressive hepatic encephalopathy (grade 3-4) to protect airway 1, 3
• Use propofol as preferred sedative due to favorable pharmacokinetics and minimal impact on encephalopathy 6
• Avoid benzodiazepines and psychotropic drugs (including metoclopramide) as they worsen encephalopathy 1, 6, 3
• Do not use empiric treatments to reduce intracranial pressure (moderate hypothermia, hypertonic saline, mannitol, hyperventilation) as RCTs showed no mortality benefit 2

Cardiovascular Management

Assess volume status with echocardiography or pulmonary artery catheterization in hemodynamically unstable patients, use crystalloid fluids as first-line for volume expansion, and administer norepinephrine for refractory hypotension to maintain mean arterial pressure of 50-60 mm Hg. 2, 1, 3

• Avoid vasopressin as it has not been validated in ALF 2
• Alpha-adrenergic agents (epinephrine, norepinephrine) and dopamine are acceptable alternatives if norepinephrine is unavailable 2

Renal Management

Use continuous renal replacement therapy rather than intermittent hemodialysis for acute kidney injury, as continuous modes improve outcomes and reduce morbidity. 2, 3

• Avoid nephrotoxic drugs including NSAIDs 6, 3
• Treat hepatorenal syndrome with terlipressin plus concentrated albumin as first-line therapy 6

Coagulation Management

Restrict clotting factor administration to cases with active bleeding only; do not routinely correct coagulation abnormalities as INR is a prognostic marker. 6, 3

Infection Control

Administer empirical broad-spectrum antibiotics to patients with worsening hepatic encephalopathy or signs of systemic inflammatory response syndrome 3

Respiratory Management

Implement standard lung-protective ventilation strategies in mechanically ventilated patients 3

Gastrointestinal Management

Provide stress ulcer prophylaxis to prevent gastrointestinal bleeding 3

Prognostic Assessment and Transplant Listing

Use MELD score with a fixed cut-off value of 30.5 rather than King's College Criteria for prognostication, as MELD offers superior sensitivity (77% vs 61%) while maintaining acceptable specificity. 2

Transplant Listing Criteria

Contact a transplant center immediately for patients with poor prognostic indicators including idiosyncratic drug injury, non-hepatitis A viral infections, autoimmune hepatitis, mushroom poisoning, Wilson disease, Budd-Chiari syndrome, or indeterminate cause. 1, 3

Acetaminophen-Induced ALF

• 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 hepatic encephalopathy 1, 3

Non-Acetaminophen ALF

• PT >100 seconds irrespective of coma grade 3
• Higher grades of encephalopathy (grade 3-4) 3

Common Pitfalls

• Do not delay transplant listing while awaiting response to medical therapy in high-risk etiologies, as 10-40% of listed patients die awaiting organs 2
• Do not use extracorporeal liver support systems outside clinical trials, as RCTs show no clear mortality benefit despite trends toward improvement 2
• Do not rely solely on acetaminophen history, as reported ingestion quantity is often inaccurate; always measure serum levels 4
• Do not restrict protein intake severely; 60 grams per day is reasonable and branched-chain amino acids offer no advantage 2

Monitoring and Follow-Up

• Monitor coagulation parameters, complete blood counts, metabolic panels, and arterial blood gases frequently throughout hospitalization 6
• Check liver function tests daily to follow disease trajectory 6
• Reassess transplant need after completing initial NAC course if acetaminophen levels remain detectable or transaminases continue rising 4