Acute liver injury & failure
ALF = acute liver injury + INR ≥1.5 + encephalopathy, no prior cirrhosis (except acute Wilson, HBV, AIH flares).
Rahul Gupta & Dan Rubin5 min6 questions2 trials
ALI vs ALF vs ACLF
Acute liver injury: liver injury <26 weeks with coagulopathy but no encephalopathy. Acute liver failure: encephalopathy plus INR ≥1.5, <26 weeks, in a patient without cirrhosis (: ; ACG: ; ). ACLF is not ALF — you will see portal hypertension and chronic-liver stigmata. Alcohol-associated hepatitis is ACLF physiology.
Presentation: fatigue, anorexia, nausea, RUQ pain, pruritus, ± jaundice → ascites and confusion as ALF declares itself.
- Initial labs: CBC with differential, CMP, PT/INR, PTT, fibrinogen, LDH, type and screen, lactate, ABG, arterial ammonia, glucose, hCG, HIV, APAP, urine/serum tox, PEth, viral and autoimmune serologies, amylase/lipase.
- CT head if encephalopathic. RUQUS with Doppler on everyone ().
Call transplant, then keep the brain alive
- Hepatology / transplant immediately. Grade 3–4 HE is not a next-morning consult.
- Serial coags, CBC, ABG, CMP, ammonia; q2 h neuro checks. Cushing triad (bradycardia, irregular respirations, wide pulse pressure) is herniation until proven otherwise.
- MAP ≥75 (NS and/or norepinephrine ± vasopressin) for cerebral perfusion.
- Intubate for HE ≥ grade 3. Cerebral edema in ~25–35% of grade 3 and ~75% of grade 4.
- Lactulose in ALF is controversial (bowel distention may worsen outcomes) — this is not cirrhotic HE.
- CRRT if HE ≥ grade 2: lowers ammonia within 3 days and mortality ().
- High herniation risk (grade 3–4, arterial NH3 >150, renal failure, pressors): 3% saline for Na 145–155 (), HOB 30°, minimize stimulation, avoid overhydration and high PEEP.
- Treat edema with mannitol 0.5–1 g/kg × 1–3. Impending herniation: hyperventilate PaCO2 ~25–30 (temporary). Barbiturates last, watching hypotension.
- Seizures: phenytoin; benzos if refractory. Low threshold for EEG (subclinical seizure).
- Infection in ~90% (Staph, Strep, GNR, fungi). Serial cultures. Worsening HE or AKI may be the only sign. Empiric antimicrobials readily; no routine prophylaxis. ICU PPI prophylaxis.
Cause-specific moves
| Cause | Clues | Move |
|---|---|---|
| Acetaminophen | Most common US ALF. Dose-dependent: >6 g/d or 150 mg/kg/d for 24–48 h; >4 g/d or 100 mg/kg/d for >48 h | Charcoal if <4 h or rising level. Empiric NAC if >30 g ingested or AST/ALT already deranged. nomogram |
| Idiosyncratic DILI / Amanita / CCl4 | Augmentin, AEDs, anti-TB; mushroom foraging | Stop the drug. Amanita: IV silibinin 20–50 mg/kg/d × 2–4 d + NAC |
| HAV / HEV | Travel, food, pregnancy (HEV) | Supportive; transplant if needed |
| HBV ± HDV / rare HCV | PWID, sex, endemic | Transplant; antivirals may help HBV |
| HSV / VZV | May be anicteric with low WBC; vesicular rash; immunocompromised | Acyclovir 5–10 mg/kg q8 h |
| Ischemia / Budd-Chiari / VOD | , cocaine/meth, hypercoagulable, post-HSCT. ALT/LDH <1.5 favors ischemia | Doppler US; anticoagulate / TIPS / lyse / transplant for Budd-Chiari |
| AIH | Women; ↑ IgG, ANA, ASMA, LKM-1 | Consider steroids; transplant if failing |
| Wilson | <40, AST:ALT often >2, low/normal ALP, ALP/Tbili <4, DAT-negative hemolysis, low uric acid, rapidly progressive AKI | Transplant. Chelation does not rescue ALF. KF rings, ceruloplasmin (may be normal/high in ALF) |
| HELLP / AFLP / infiltrate / HLH / heat stroke | Pregnancy, breast CA / SCLC / lymphoma, fever | . Biopsy if still lost |
West Haven in ALF, King’s College, prognosis
Same names as cirrhotic West Haven — completely different physiology. ALF HE is cerebral edema and herniation. Cirrhotic HE is not.
| Grade | Mental status | Asterixis |
|---|---|---|
| I | Attention deficit, mild confusion | ± |
| II | Lethargy, moderate confusion | Present |
| III | Somnolence, marked confusion, responsive to stimuli | Present |
| IV | Coma | Usually lost |
| King’s College — list for transplant | Criteria (specific, not sensitive) |
|---|---|
| APAP-ALF | Arterial pH <7.3, OR all three: INR >6.5 + Cr >3.4 + grade III–IV HE |
| Non-APAP ALF | INR >6.5, OR 3 of 5: age <10 or >40; Tbili ≥17; INR >3.5; jaundice-to-encephalopathy >7 d; unfavorable etiology (seronegative hepatitis, DILI, Wilson) |
- MELD >25 = poor prognosis. HBV, Wilson, Budd-Chiari, AIH, and DILI also track poorly.
- Complications: HE/edema, high-output , pulmonary edema/ARDS, GIB, APAP-associated pancreatitis, hypoglycemia, adrenal insufficiency, renal failure in >50%, lactate acidosis, hyponatremia, hypokalemia, hypophosphatemia, coagulopathy, thrombocytopenia, DIC, infection.