Acute liver failure (ALF) is defined by the triad: (1) Coagulopathy (INR ≥1.5), (2) Hepatic encephalopathy (any grade), and (3) No prior liver disease, with illness duration <26 weeks. It is a medical emergency with mortality >50% without transplant in many etiologies.
Etiology-specific workup should be sent simultaneously on arrival:
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| N-acetylcysteine (NAC) | ALL ALF, first-line | 150 mg/kg IV over 1h → 50 mg/kg over 4h → 100 mg/kg over 16h | Continue until INR <1.5 or transplant. Improves transplant-free survival even in NON-acetaminophen ALF. Lee, Gastroenterology 2009 |
| Mannitol 20% | Cerebral edema / herniation | 0.5-1 g/kg IV bolus | Use if serum osm <320. Can repeat x1. Monitor serum osmolality. |
| Hypertonic saline (3% or 23.4%) | Cerebral edema prophylaxis | 3% NaCl infusion targeting Na 145-155 | Prophylactic hypernatremia reduces cerebral edema incidence. 23.4% (30 mL) for acute herniation. |
| Dextrose 10% (D10) | Hypoglycemia prevention | Continuous drip at 75-100 mL/h | Check glucose q1-2h. Hepatic gluconeogenesis fails, hypoglycemia is common and dangerous. |
| Lactulose | Hepatic encephalopathy | 30 mL PO/NG q2h titrated to 3-4 BMs/day | Role in ALF is less established than in cirrhotic HE, but often given. Avoid excessive diarrhea (volume depletion). |
| Piperacillin-tazobactam | Empiric antibiotics | 4.5 g IV q6h | Low threshold. Infection in up to 80%. Fungal prophylaxis (fluconazole) may be warranted. |
Patient: 28F presents with 5 days of nausea, vomiting, and jaundice. Reports taking "extra-strength Tylenol" ~4-6 g/day for 10 days for back pain. No prior liver disease.
Key findings: HR 110, BP 95/60, confused with asterixis (Grade II HE). ALT 8,400, AST 10,200, total bilirubin 8.5, INR 4.8, Cr 2.1, pH 7.28, lactate 6.2, acetaminophen level 45 mcg/mL.
Management:
Teaching point: Acetaminophen ALF has the best prognosis if treated promptly with NAC. Unintentional supratherapeutic dosing is more common than intentional overdose. Never correct INR prophylactically -- it masks prognosis.
Patient: 35F with no prior history, presents with 2 weeks of fatigue, jaundice, and dark urine. Now confused and unable to follow commands. PMH: Hashimoto thyroiditis.
Key findings: Jaundiced, Grade III HE. ALT 2,100, AST 1,800, total bilirubin 22, INR 3.6, IgG 3,200 (markedly elevated), ANA 1:640, anti-smooth muscle antibody positive. Viral hepatitis serologies negative.
Management:
Teaching point: NAC benefits ALL causes of ALF, not just acetaminophen. Autoimmune hepatitis causing ALF can receive a steroid trial, but do not delay transplant evaluation. Elevated IgG + autoantibodies in a young woman = think autoimmune.
Patient: 22M presents with acute jaundice, confusion, and dark urine x 1 week. No medications. Sister diagnosed with Wilson disease at age 18.
Key findings: Kayser-Fleischer rings on slit lamp. AST 1,400, ALT 600 (AST:ALT > 2.2), ALP 45 (paradoxically LOW), total bilirubin 32, INR 5.2. Ceruloplasmin 8 (low). Hgb 7.2 with Coombs-negative hemolytic anemia (reticulocytes 8%, haptoglobin < 10, LDH 890). 24h urine copper 1,200 mcg.
Management:
Teaching point: Wilson ALF has a classic triad: Coombs-negative hemolytic anemia + very low ALP + AST:ALT > 2.2. The ALP:bilirubin ratio < 4 is highly specific. This is a transplant emergency -- chelation does not work fast enough.
Mrs. Patel is a 28-year-old woman presenting with 5 days of nausea, vomiting, and jaundice, now with confusion and asterixis. She reports taking "extra-strength Tylenol" for back pain, approximately 4-6 g/day for the past week. VS: T 37.2, HR 110, BP 95/60, RR 22. Labs: ALT 8,400, AST 10,200, total bilirubin 8.5, INR 4.8, Cr 2.1, acetaminophen level 45 mcg/mL, pH 7.28, lactate 6.2, ammonia 98. Hepatitis serologies pending. NAC drip started immediately. Transplant hepatology notified.