›Dosing
›400 mg PO three times daily for 28 days
›Evidence has weakened
›Early single center trial suggested reduced hepatorenal syndrome incidence and short term mortality
›Larger multicenter randomized trial did not confirm survival benefit over placebo or over prednisolone
›Not currently recommended as first line or as an addition to corticosteroids
›May be considered when corticosteroids are contraindicated, though evidence for benefit alone is weak
›Contraindications
›Active hemorrhage
›Recent cerebral or retinal hemorrhage
›Intravenous N-acetylcysteine
›Dosing when used as corticosteroid adjunct
›150 mg/kg IV over 1 hour
›Then 50 mg/kg IV over 4 hours
›Then 100 mg/kg IV over 16 hours daily for 5 days total
›Evidence
›Combination with corticosteroids improved 1 month survival in a randomized trial
›No demonstrated benefit at 6 months
›Not established as monotherapy without corticosteroids
›Rationale
›Glutathione precursor reduces oxidative stress contributing to hepatocyte injury
›Nutritional support
›Early enteral nutrition
›Target 35 to 40 kcal/kg/day
›Protein 1.2 to 1.5 g/kg/day, avoid protein restriction
›Malnutrition severity independently predicts mortality
›Oral nutritional supplementation if intake inadequate
›NG feeding if oral intake persistently insufficient
›Refeeding syndrome precaution
›Check phosphate, potassium, magnesium before and during refeeding
›Correct deficits before advancing caloric intake
›ECG monitoring for arrhythmia if severe hypophosphatemia or hypokalemia develops
›Thiamine and micronutrients
›Thiamine 200 mg IV daily
›Given before or with any glucose containing fluids
›Prevents precipitating Wernicke encephalopathy, see Wernicke's Encephalopathy management for full dosing in suspected cases
›Folate and multivitamin repletion
›Electrolyte correction
›Potassium repletion in mmol IV for hypokalemia
›Reduces renal ammonia generation, aids encephalopathy control
›Sodium phosphate or potassium phosphate repletion in mmol IV for hypophosphatemia
›Hyponatremia correction limited to 8 mmol/L or less per 24 hours
›Limit to 6 mmol/L or less per 24 hours in malnourished or actively drinking patients
›Osmotic demyelination syndrome risk with rapid correction
Concurrent alcohol withdrawal and hepatic encephalopathy management
›Alcohol withdrawal
›Symptom triggered benzodiazepine protocol
›See Alcohol withdrawal / Ethanol Withdrawal management for CIWA-Ar scoring and full dosing
›Preferred agents in liver disease
›Lorazepam or oxazepam, glucuronidated and not hepatically oxidized
›Avoid diazepam and chlordiazepoxide, accumulate with impaired hepatic clearance
›Distinguishing from hepatic encephalopathy
›Autonomic hyperactivity and hallucinations favor withdrawal
›Isolated lethargy without autonomic signs favors hepatic encephalopathy
›Both may coexist, treat both pathways simultaneously when uncertain
›Hepatic encephalopathy
›Lactulose first line
›See Hepatic encephalopathy management for full dosing, precipitant screen, and rifaximin protocol
›Precipitant screen specific to alcoholic hepatitis
›Infection, GI bleeding, hypokalemia, constipation, sedative exposure
Hepatorenal syndrome management
›Recognition
›Progressive creatinine rise without another identifiable cause
›See Hepatorenal syndrome management for full diagnostic criteria and staging
›Terlipressin
›Dosing
›0.5 to 1 mg IV every 4 to 6 hours
›Increase to 2 mg IV every 4 to 6 hours if creatinine does not fall by 30 percent or more by day 3
›Maximum duration approximately 14 days
›Given with albumin
›20 to 40 g IV daily
›Volume status reassessed daily
›Monitoring
›Daily creatinine trend
›Cardiac monitoring for ischemia, terlipressin can precipitate coronary or peripheral ischemia
›Alternative regimen when terlipressin unavailable
›Midodrine
›7.5 to 12.5 mg PO three times daily
›Titrate up to maximum 15 mg three times daily
›Octreotide
›100 to 200 mcg SC three times daily, or continuous infusion 25 to 50 mcg/hour
›Combined with albumin as above
›Norepinephrine alternative in ICU setting
›Continuous infusion titrated to raise mean arterial pressure by approximately 10 mmHg
›Typical range 0.5 to 3 mcg/kg/minute
Iatrogenic harms and routine ED intervention modifications
›Intubation
›Aspiration risk elevated with encephalopathy or active emesis
›Reduced induction dosing for hypoalbuminemia
›Not otherwise contraindicated, proceed when airway threatened
›Sedation
›Benzodiazepine accumulation risk
›Prefer lorazepam or oxazepam over hepatically oxidized agents
›Can precipitate or mask hepatic encephalopathy
›Fluid loading
›Normal saline sodium load worsens ascites and portal hypertension
›Prefer balanced crystalloid in modest volumes, albumin for oncotic support in SBP or large volume paracentesis
›Oxygen
›Standard target SpO2 92 to 96 percent
›Hepatopulmonary syndrome exception, baseline hypoxemia may be chronic, target individualized with hepatology input
›Vasopressors
›Norepinephrine first line
›Avoid vasopressin, arrhythmia and sudden death risk in cirrhotic patients
›Terlipressin specific to hepatorenal syndrome, not general shock
›Mechanical circulatory support including intra-aortic balloon pump
›No established role in alcoholic hepatitis
›Not indicated absent a separate cardiac indication
›Anticoagulation
›Elevated INR does not confer bleeding protection
›VTE prophylaxis generally still indicated unless active bleeding or severe thrombocytopenia
›Mechanical prophylaxis preferred if bleeding risk high
›Fibrinolysis
›Relative contraindication given coagulopathy, thrombocytopenia, and possible occult varices
›Discuss with hepatology before use for a separate indication such as stroke or massive PE
›Analgesia and antipyretics
›Acetaminophen
›Maximum 2 g per day if used, avoid entirely during active heavy drinking
›Combined ethanol and acetaminophen hepatotoxicity risk
›NSAIDs
›Avoid, renal injury risk, GI bleeding risk, sodium retention worsens ascites
›Opioids
›Reduced dose and frequency, avoid extended release formulations
›Fentanyl preferred, no active toxic metabolite accumulation with hepatic impairment
›Avoid in active hepatic encephalopathy
Transplant evaluation pathway
›Standard pathway
›Historical fixed 6 month abstinence requirement
›Increasingly replaced by individualized psychosocial assessment
›Early liver transplantation
›Selected first episode severe alcoholic hepatitis without steroid response
›Lille score 0.45 or greater after adequate corticosteroid trial
›Multidisciplinary psychosocial evaluation required before listing
›Landmark trial demonstrated improved survival with early transplant in tightly selected patients versus continued medical therapy
›Not appropriate for patients with repeated relapses or lack of psychosocial support
›Referral timing
›Early referral once Lille score non-response confirmed
›Do not delay transplant discussion to an arbitrary sobriety interval