361.1 🎓 醫學生版

361.1.0.1 📌 一頁重點

361.1.0.1.1 Definition

• Severe acute liver injury
• Encephalopathy (hallmark)
• Coagulopathy (INR ≥ 1.5)
• No preexisting liver disease (or compensated cirrhosis acceptable in some definitions)
• < 26 weeks from onset

361.1.0.1.2 Classification by Time

Type	Jaundice → HE	Characteristics
Hyperacute	< 7 days	Cerebral edema common, paradoxically better spontaneous recovery
Acute	7-21 days	Intermediate
Subacute	21 days - 26 weeks	Worse prognosis, ascites, less edema

361.1.0.1.3 Etiology

361.1.1 Drug-Induced

• Acetaminophen (top US/UK; ~ 50%)
• Idiosyncratic DILI:
  • Antibiotics: amoxicillin-clavulanate, isoniazid, nitrofurantoin
  • Anticonvulsants: phenytoin, valproate
  • Statins (rare)
  • Herbals + supplements (kava, green tea extract, anabolic steroids)
• Methotrexate, propylthiouracil

361.1.2 Viral

• HAV — usually self-limited but can cause ALF
• HBV — particularly with HDV coinfection
• HEV — pregnancy (especially 3rd trimester, 20% mortality)
• HCV — rarely
• HSV — pregnancy + immunocompromised
• VZV, CMV, EBV, parvovirus B19

361.1.3 Toxic

• Amanita phalloides mushroom
• Carbon tetrachloride
• Industrial solvents

361.1.4 Vascular

• Budd-Chiari syndrome
• Ischemic hepatitis (shock liver)
• Venoocclusive disease

361.1.5 Metabolic

• Wilson disease (often fulminant)
• Reye syndrome (children with aspirin + viral)

361.1.6 Pregnancy

• HELLP syndrome
• Acute fatty liver of pregnancy (AFLP)

361.1.7 Autoimmune

• AIH can present as ALF

361.1.8 Malignancy

• Massive infiltration
• Lymphoma

361.1.9 Idiopathic

• ~ 15% unknown

361.1.9.0.1 Clinical Features

361.1.10 Hepatic Encephalopathy Grading (West Haven)

Grade	Features
I	Mild confusion, irritability, sleep disturbance
II	Drowsy, disoriented, asterixis, inappropriate behavior
III	Stuporous but arousable, marked confusion, asterixis difficult
IV	Coma

361.1.11 Cerebral Edema

• Major cause of death
• More common with hyperacute
• Causes ↑ ICP
• Brain herniation

361.1.12 Coagulopathy

• ↓ all factors except VIII
• INR ≥ 1.5
• Bleeding less common than INR suggests (also ↓ anticoagulant factors)

361.1.13 Hypoglycemia

• ↓ gluconeogenesis
• Frequent monitoring needed

361.1.14 Renal Failure

• Hepatorenal vs ATN vs prerenal
• Common
• May require RRT

361.1.15 Sepsis + SIRS

• High infection risk
• Multiple organisms
• Bacterial + fungal

361.1.16 CV

• High output state
• Vasodilation
• Eventually hypotension

361.1.17 Pulmonary

• ARDS
• Atelectasis
• Pneumonia
• Often need ventilation

361.1.18 Lactic Acidosis

• Marker of severity

361.1.18.0.1 Workup

361.1.19 Etiology

• Acetaminophen level + history
• Viral hepatitis: HAV IgM, HBsAg + anti-HBc IgM, HCV RNA, HEV IgM, HSV PCR
• Autoimmune: ANA, anti-SMA, anti-LKM-1, IgG, anti-LC1
• Wilson: ceruloplasmin, urine copper, slit lamp (KF rings), liver biopsy
• Pregnancy test (women)
• Doppler US: hepatic veins (Budd-Chiari)
• CT/MRI: rule out malignancy, vascular
• Mushroom history

361.1.20 Severity

• INR (best marker of synthetic function)
• Bilirubin
• Lactate
• Creatinine
• Glucose
• ABG
• Phosphate (recovery — ↓ in regenerating liver)

361.1.20.0.1 Prognosis

361.1.21 King’s College Criteria

Acetaminophen-Induced: - pH < 7.30 (irrespective of HE grade) OR - All of: INR > 6.5 + creatinine > 3.4 + grade III/IV HE

Non-Acetaminophen: - INR > 6.5 OR - Any 3 of: - Age < 10 or > 40 - Non-A non-B hepatitis, drug-induced, halothane - Duration jaundice → HE > 7 days - INR > 3.5 - Bilirubin > 17.6 mg/dL

361.1.22 Other Predictors

• MELD ≥ 30 also indicator
• Lactate > 3.5 mmol/L (Bernal)
• Phosphate trend (low = recovery)

361.1.22.0.1 Management

361.1.23 General ICU

• ICU admission
• Airway protection (grade III-IV HE)
• Mechanical ventilation as needed
• Hemodynamic support
• Frequent glucose monitoring
• Coagulation monitoring
• Sepsis screening

361.1.24 Etiology-Specific

361.1.24.1 Acetaminophen

• N-acetylcysteine (NAC)
• IV regimen: 150 mg/kg over 1 hr → 50 mg/kg over 4 hr → 100 mg/kg over 16 hr
• Effective even if late presentation
• Continue until normalization

361.1.24.2 Non-Acetaminophen ALF

• NAC benefit even in non-acetaminophen ALF (Lee 2009)
• Improves transplant-free survival in early stages (I-II HE)
• IV NAC × 72 hours

361.1.24.3 Viral

• HBV: entecavir or tenofovir
• HSV: acyclovir
• HEV: supportive

361.1.24.4 Wilson

• Penicillamine (limited role in ALF)
• Plasmapheresis
• Almost always need transplant

361.1.24.5 Mushroom (Amanita)

• Silibinin (silymarin IV)
• NAC
• Penicillin G
• Gastric lavage if recent

361.1.24.6 Autoimmune

• Steroids (limited evidence in ALF)
• Transplant for severe

361.1.24.7 Budd-Chiari

• Anticoagulation
• TIPS
• Transplant if severe

361.1.25 Cerebral Edema Management

• Head of bed 30°
• Mannitol 0.5-1 g/kg IV bolus
• Hypertonic saline (3%) to Na 145-150
• Hyperventilation acutely
• ICP monitoring controversial (coagulopathy risk)
• Target: ICP < 20, CPP > 60
• Avoid hypotension
• Treat fever
• Minimize stimulation

361.1.26 Coagulopathy

• Avoid routine FFP (interferes with INR monitoring)
• Treat active bleeding or pre-procedure
• Vitamin K (cofactor)
• Platelets if low + bleeding
• Cryoprecipitate if fibrinogen low

361.1.27 Renal

• RRT (CRRT preferred for hemodynamics)
• Treat HRS

361.1.28 Sepsis

• Empiric broad-spectrum
• Surveillance cultures
• Antifungal prophylaxis

361.1.29 Nutrition

• Enteral preferred
• 1.0-1.5 g/kg protein
• No protein restriction routinely
• Avoid hypoglycemia

361.1.30 Liver Support Devices

• MARS, Prometheus
• Limited evidence for survival benefit
• Bridge to transplant

361.1.31 Liver Transplantation

• Definitive therapy for severe ALF
• Status 1A in US
• King’s College Criteria identify candidates
• 1-yr survival 80-85%
• 5-yr 70%

361.1.31.0.1 Outcomes

361.1.32 Spontaneous Recovery

• Acetaminophen: ~ 65%
• HAV: ~ 60%
• HBV: ~ 25%
• Idiosyncratic DILI: ~ 25%
• Wilson: < 10%
• Idiopathic: ~ 25%

361.1.33 With Transplant

• 1-yr 80-85%
• 5-yr 70%

361.1.34 Without Transplant

• Varies widely by etiology
• ~ 40% overall

361.1.34.1 🩺 床邊速查

• ALF triad: encephalopathy + coagulopathy (INR ≥ 1.5) + no preexisting liver disease, < 26 weeks
• Top cause US: acetaminophen
• Workup: acetaminophen level + viral serology + autoimmune + ceruloplasmin + pregnancy test + Doppler
• King’s College Criteria for transplant decision
• NAC for acetaminophen + early non-acetaminophen ALF
• Cerebral edema = major cause of death; mannitol + hypertonic saline
• Transplant Status 1A; 1-yr 80-85%

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