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hep.acute-liver-failure.core.v1PRODUCTION
hep.acute-liver-failure.core.v1

Acute Liver Failure

hepatologyacuteadult
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Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Confirm ALF scope: INR >=1.5 + encephalopathy + no chronic liver disease + <26 wk duration (AASLD ALF)

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Advance rule
Set
Advance when

ALF criteria met

Patient inputs (20)

Viral ALF workup (anti-HAV IgM, HBsAg + anti-HBc IgM, HCV RNA, HEV IgM) (AASLD ALF)

Age <11 or >40 = adverse Kings College non-APAP criterion (OGrady 1989)

Distributive shock + cerebral perfusion pressure; MAP >=75 target for cerebral edema

Hypothermia 35-36C neuroprotective; hyperthermia worsens ICP

DILI/HDS most common non-APAP cause; LiverTox database (Stravitz Lee 2019)

AFLP, HELLP, eclamptic ALF differential in women of reproductive age (AASLD ALF)

INR >=1.5 = ALF diagnostic criterion; Kings College component (AASLD ALF)

Kings College non-APAP component; severity marker (OGrady 1989)

Kings College APAP component (Cr >3.4 mg/dL); HRS risk (OGrady 1989)

Kings College APAP component (pH <7.30 after resuscitation) (OGrady 1989)

Kings College APAP component (lactate >3.5 early or >3.0 post-resus) (Bernal 2002)

Pattern recognition: AST/ALT >5000 = ischemia; >1000 with ALT>AST = APAP/viral (Stravitz Lee 2019)

Identifies treatable APAP toxicity; Rumack-Matthew nomogram

Rule out Budd-Chiari, portal vein thrombosis, biliary obstruction (Stravitz Lee 2019)

ARDS / aspiration risk in HE grade 3-4; intubation trigger

Hypoglycemia from hepatic gluconeogenesis failure; D10 infusion (Stravitz Lee 2019)

Wilson disease workup in <40yo with hemolytic anemia + ALP/bilirubin ratio <4 (Korman 2008)

Rule out structural brain lesion + assess cerebral edema in HE grade 3-4 (AASLD ALF)

Arterial NH3 >150 micromol/L predicts cerebral edema and intracranial HTN (Bernal Wendon 2013)

Low phosphorus = regeneration; high phosphorus = poor prognosis (Schmidt 2002)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningkings_college_apap_met
    Kings College APAP criteria: arterial pH <7.30 after adequate resuscitation OR (INR >6.5 AND Cr >3.4 mg/dL AND HE grade 3-4) (OGrady 1989)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningkings_college_non_apap_met
    Kings College non-APAP: INR >6.5 OR any 3 of (age <11 or >40, non-A/non-B/DILI, jaundice-to-HE >7d, INR >3.5, bilirubin >17.5 mg/dL) (OGrady 1989)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningcerebral_edema_he_grade_4
    HE grade 4 (coma, posturing, papilledema) OR arterial NH3 >150 micromol/L OR herniation signs (Bernal Wendon 2013)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateninglactate_post_resuscitation
    Arterial lactate >3.0 mmol/L 12h post-fluid resuscitation OR >3.5 mmol/L early in APAP ALF (Bernal 2002)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningwilson_alf_phenotype
    Hemolytic Coombs-negative anemia + ALP:bili ratio <4 + AST:ALT >2.2 in patient <40yo (Korman 2008)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningafp_hellp_pregnancy_alf
    Pregnant patient with ALF (AFLP, HELLP, eclamptic liver) (Stravitz Lee 2019)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevererefractory_hypoglycemia
    Glucose <70 mg/dL despite D10 infusion (Stravitz Lee 2019)
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Acute liver failure - NAC for all + etiology-specific therapy + cerebral edema bundle (AASLD ALF + Stravitz Lee 2019)
axis: alf_etiology_stratified_pathwaystep 1 - Step 1 - N-acetylcysteine for ALL ALF (etiology-agnostic)
Selected step "Step 1 - N-acetylcysteine for ALL ALF (etiology-agnostic)" — Confirmed ALF regardless of etiology; greatest benefit in HE grade 1-2 (Lee 2009)
  • acetylcysteine
    first line
    antioxidant_glutathione_precursor
    150 mg/kg IV in D5W over 60 min, then 50 mg/kg over 4h, then 100 mg/kg over 16h (21h Prescott protocol); continue 6.25 mg/kg/h until INR <1.5 or transplant or death • IV • continuous infusion
    triggers: ALF_any_etiology, APAP_overdose
    AASLD ALF Class I for APAP; Lee 2009 (Gastroenterology PMID 19524577) demonstrated transplant-free survival benefit in non-APAP ALF coma grades I-II
    rxcui 197

ed playbook — drug actions (4)

  1. 1. N-acetylcysteine
    150 mg/kg IV over 60 min then 50 mg/kg over 4h then 100 mg/kg over 16h then 6.25 mg/kg/h continuous • IV • continuous
    trigger: Any ALF; do NOT wait for etiology (Lee 2009)
    AASLD ALF Class I for APAP; transplant-free survival benefit in non-APAP ALF coma I-II (Lee 2009)
  2. 2. D10 dextrose infusion
    D10W titrated to glucose >=70 mg/dL • IV • continuous
    trigger: Hypoglycemia (common from hepatic gluconeogenesis failure) (Stravitz Lee 2019)
    Hypoglycemia worsens cerebral injury
  3. 3. thiamine
    100-500 mg IV before dextrose if AUD • IV • before glucose
    trigger: AUD or malnutrition (Stravitz Lee 2019)
    Wernicke prophylaxis
  4. 4. piperacillin-tazobactam empiric
    4.5 g IV q6h • IV • q6h
    trigger: Suspected sepsis or HE grade 3-4 (AASLD ALF)
    High infection rate

Auto-drafted A&P note

ed

Subjective

- Possible entry pathways: INR >=1.5 in patient without known chronic liver disease (AASLD ALF); New-onset hepatic encephalopathy / altered mental status (AASLD ALF); Rapid-onset jaundice + coagulopathy in previously healthy patient (Stravitz Lee 2019).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Acute Liver Failure** (hep.acute-liver-failure.core.v1).
Phenotype framing: Categorize: acetaminophen (50% US), DILI/HDS (11%), indeterminate (11%), viral (HAV/HBV/HEV) (12%), autoimmune (5-7%), Wilson, Budd-Chiari, ischemic, AFLP/HELLP, mushroom (Amanita), malignant infiltration (Stravitz Lee 2019)
Scope: Confirm ALF scope: INR >=1.5 + encephalopathy + no chronic liver disease + <26 wk duration (AASLD ALF)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Acute liver failure - NAC for all + etiology-specific therapy + cerebral edema bundle (AASLD ALF + Stravitz Lee 2019)** — step "Step 1 - N-acetylcysteine for ALL ALF (etiology-agnostic)".
1. acetylcysteine 150 mg/kg IV in D5W over 60 min, then 50 mg/kg over 4h, then 100 mg/kg over 16h (21h Prescott protocol); continue 6.25 mg/kg/h until INR <1.5 or transplant or death IV continuous infusion (antioxidant_glutathione_precursor, first line) — AASLD ALF Class I for APAP; Lee 2009 (Gastroenterology PMID 19524577) demonstrated transplant-free survival benefit in non-APAP ALF coma grades I-II

Setting playbook (ed) — Recognize ALF (INR >=1.5 + encephalopathy + no chronic liver disease), start NAC immediately, rule out APAP overdose, contact nearest liver transplant center for transfer (AASLD ALF; Stravitz Lee 2019)
2. N-acetylcysteine 150 mg/kg IV over 60 min then 50 mg/kg over 4h then 100 mg/kg over 16h then 6.25 mg/kg/h continuous IV continuous — Any ALF; do NOT wait for etiology (Lee 2009) (AASLD ALF Class I for APAP; transplant-free survival benefit in non-APAP ALF coma I-II (Lee 2009))
3. D10 dextrose infusion D10W titrated to glucose >=70 mg/dL IV continuous — Hypoglycemia (common from hepatic gluconeogenesis failure) (Stravitz Lee 2019) (Hypoglycemia worsens cerebral injury)
4. thiamine 100-500 mg IV before dextrose if AUD IV before glucose — AUD or malnutrition (Stravitz Lee 2019) (Wernicke prophylaxis)
5. piperacillin-tazobactam empiric 4.5 g IV q6h IV q6h — Suspected sepsis or HE grade 3-4 (AASLD ALF) (High infection rate)

Non-pharmacologic actions:
- IV access x 2 large bore (AASLD ALF)
- NPO + foley if HE grade 3-4 (AASLD ALF)
- Head of bed 30deg if cerebral edema concern (Bernal Wendon 2013)
- Intubation for HE grade 3-4 or airway compromise (AASLD ALF)
- Avoid sedatives/benzos if not intubated (AASLD ALF)
- Contact transplant center NOW for UNOS Status 1A listing eligibility (AASLD ALF)
- STAT transfer to liver transplant center if not at one (AASLD ALF)

AVOID / contraindication checks:
- NSAID_avoid_in_ALF_renal_GI_bleed_risk (AASLD ALF)
- Benzodiazepine_avoid_or_minimize_HE_precipitant (AASLD ALF)
- Lactulose_controversial_in_ALF_may_worsen_ICP_via_gas (AASLD ALF)
- Nephrotoxin_avoid_aminoglycoside_contrast (AASLD ALF)
- Acetaminophen_avoid_unless_NAC_protocol (AASLD ALF)
- Hypoosmolar_fluid_avoid_worsens_cerebral_edema_use_isotonic_or_hypertonic (Bernal Wendon 2013)

Monitoring

Regimen monitoring:
- q1h neuro checks West Haven grade (AASLD ALF)
- continuous arterial BP MAP target >=75 (AASLD ALF)
- q1h glucose initial then q2 4h (Stravitz Lee 2019)
- q4h INR bilirubin Cr ammonia lactate (AASLD ALF)
- serum Na q6h target 145 150 if cerebral edema (Bernal Wendon 2013)
- daily MELD recalculation (AASLD ALF)
- transcranial doppler for cerebral blood flow (Stravitz Lee 2019)
- ICP monitor for selected HE 4 at transplant center (AASLD ALF)
- blood cultures q48h (AASLD ALF)
- surveillance cultures for fungal infection (AASLD ALF)

Setting (ed) monitoring:
- Continuous SpO2 + telemetry (AASLD ALF)
- q1h neuro checks (West Haven) (AASLD ALF)
- Glucose POC q1h initial (Stravitz Lee 2019)
- Repeat INR / ammonia / lactate q4h (AASLD ALF)

Follow-up plan: Survivors: hepatology follow-up; counseling on hepatotoxin avoidance (APAP <2 g/day if at-risk; alcohol abstinence); LiverTox reporting for DILI; vaccinations (HAV/HBV/influenza/pneumococcal); transplant recipients per transplant center protocol (Stravitz Lee 2019)
- Close-out criterion: follow-up scheduled

Monitoring phase: q1h neuro checks (HE grading), continuous arterial BP, hourly glucose initially, q4h NH3 / lactate / Cr / INR, MELD trend; ICP monitor for selected; serial transcranial Doppler for cerebral edema (Bernal Wendon 2013)

Disposition

Current setting: ed — Recognize ALF (INR >=1.5 + encephalopathy + no chronic liver disease), start NAC immediately, rule out APAP overdose, contact nearest liver transplant center for transfer (AASLD ALF; Stravitz Lee 2019)

Disposition criteria:
- Admit ICU at transplant center: all ALF (AASLD ALF)
- Transfer to transplant center: any ALF not at one (AASLD ALF)

Escalation triggers (move to higher acuity):
- HE grade 3-4 with airway compromise - intubate + ICU (AASLD ALF)
- Refractory hypoglycemia - D10 continuous + ICU (Stravitz Lee 2019)
- Kings College criteria met - emergent transplant evaluation (OGrady 1989)
- pH <7.30 post-resuscitation - transplant urgent (OGrady 1989)
- Lactate >3.5 mmol/L post-resuscitation - transplant urgent (Bernal 2002)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Kings College APAP criteria: arterial pH <7.30 after adequate resuscitation OR (INR >6.5 AND Cr >3.4 mg/dL AND HE grade 3-4) (OGrady 1989)
- [LIFE_THREATENING] Kings College non-APAP: INR >6.5 OR any 3 of (age <11 or >40, non-A/non-B/DILI, jaundice-to-HE >7d, INR >3.5, bilirubin >17.5 mg/dL) (OGrady 1989)
- [LIFE_THREATENING] HE grade 4 (coma, posturing, papilledema) OR arterial NH3 >150 micromol/L OR herniation signs (Bernal Wendon 2013)

Citations

- AASLD Position Paper: The Management of Acute Liver Failure (Polson Lee 2005) + Stravitz Lee Lancet Acute Liver Failure 2019 (current floor; AASLD ALF Guidance 2023 web update in progress) [PMID:15841455](https://pubmed.ncbi.nlm.nih.gov/15841455/)
- Cited evidence (PMID 31498101) [PMID:31498101](https://pubmed.ncbi.nlm.nih.gov/31498101/)
- Cited evidence (PMID 24369077) [PMID:24369077](https://pubmed.ncbi.nlm.nih.gov/24369077/)
- Cited evidence (PMID 19524577) [PMID:19524577](https://pubmed.ncbi.nlm.nih.gov/19524577/)
- Cited evidence (PMID 2490426) [PMID:2490426](https://pubmed.ncbi.nlm.nih.gov/2490426/)

Last reconciled with current guidelines: 2026-05-26.
References
  • AASLD Position Paper: The Management of Acute Liver Failure (Polson Lee 2005) + Stravitz Lee Lancet Acute Liver Failure 2019 (current floor; AASLD ALF Guidance 2023 web update in progress) — PMID:15841455
  • Cited evidence (PMID 31498101) — PMID:31498101
  • Cited evidence (PMID 24369077) — PMID:24369077
  • Cited evidence (PMID 19524577) — PMID:19524577
  • Cited evidence (PMID 2490426) — PMID:2490426