Alcoholic Hepatitis

Aka: Alcoholic Hepatitis, Alcoholic Liver Disease, Acute Alcoholic Hepatitis

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II. Epidemiology

  1. Alcoholic Hepatitis seen in 33% of chronic Alcoholics
  2. Accounted for 0.8% of hospital admissions in U.S., 2010

III. Precautions

  1. Acute Alcoholic Hepatitis, although often asymptomatic, may be severe and life threatening

IV. Pathophysiology

  1. Chronic Alcoholic Hepatitis is a precursor to Cirrhosis
  2. Characteristics
    1. Hepatocyte Inflammation, degeneration, and necrosis
    2. Neutrophil and Lymphocyte infiltration

V. Risk Factors

  1. Prolonged and heavy Alcohol use
  2. Female gender
  3. Younger age
  4. Family History
  5. High Body Mass Index
  6. Comorbid liver disease

VI. HIstory: Substance Use

  1. See Substance Abuse Evaluation
  2. See Alcoholism Screening
  3. Tools
    1. AUDIT-C
    2. CAGE Questions
    3. NIAAA Quantity and Frequency Questionnaire

VII. Symptoms: Acute Alcoholic Hepatitis

  1. Anorexia
  2. Nausea and Vomiting
  3. Weight loss
  4. Fever
  5. Fatigue
  6. Malaise
  7. Abdominal Pain
    1. Generalized Abdominal Pain
    2. Epigastric Pain
    3. Right Upper Quadrant Abdominal Pain

VIII. Signs: Acute Alcoholic Hepatitis

  1. Tender Hepatomegaly (80-90% of cases)
  2. Jaundice
  3. Ascites
  4. Splenomegaly
  5. Other findings or chronic stigmata may be present
    1. Spider Angioma
    2. Confusion (Hepatic Encephalopathy)
    3. Loss of Muscle mass
    4. Peripheral Neuropathy
    5. Day night reversal

IX. Labs

  1. Alcoholic Hepatitis Diagnostic findings
    1. Total Serum Bilirubin >3 mg/dl (>51.3 uMol/L)
    2. Transaminase increase (Aspartate Aminotransferase, Alanine Aminotransferase)
      1. AST >50 U/L (>0.83 ukat/L) AND
      2. AST/ALT >1.5 AND
      3. AST <400 U/L (<6.68 ukat/L) AND
      4. ALT <400 U/L (<6.68 ukat/L)
  2. Other liver test findings
    1. See Fibrosis Probability Score
    2. Prolonged INR (or ProTime)
    3. Alkaline Phosphatase elevated
    4. Gamma Glutamyl Transferase (GGT) markedly elevated
    5. Hypoalbuminemia (decreased Serum Albumin and Serum Prealbumin)
    6. Complete Blood Count
      1. White Blood Cell Count increased (mean 12.4k, but may range up to 20k)
      2. Mean Corpuscular Volume (MCV) elevated (Macrocytosis)
      3. Thrombocytopenia

X. Diagnosis

  1. Criteria (all must be present)
    1. No confounding factors (see below)
    2. Jaundice onset within prior 8 weeks
    3. Total Serum Bilirubin >3 mg/dl (>51.3 uMol/L)
    4. Transaminase increase
      1. AST >50 U/L (>0.83 ukat/L) AND
      2. AST/ALT >1.5 AND
      3. AST <400 U/L (<6.68 ukat/L) AND
      4. ALT <400 U/L (<6.68 ukat/L)
    5. Heavy Alcohol Use for >6 months (and <60 days of abstinence) before Jaundice onset
      1. Women with 3 standard drinks per day (>40 g)
      2. Men with 4 standard drinks per day (>60 g)
  2. Confounding Factors (possible alternative diagnoses)
    1. Ischemic Hepatitis
      1. Severe upper gastrointestinal Hemorrhage
      2. Hypotension
      3. Cocaine use within 7 days of symptom onset
    2. Metabolic Liver Disease
      1. Wilson Disease
      2. Hemochromatosis
      3. Alpha-1-Antitrypsin Deficiency
    3. Drug-Induced Liver Disease
      1. Use of suspected Hepatotoxin within 30 days of Jaundice onset
    4. Uncertain Alcohol use assessment
      1. Patient denies use that meets above criteria
    5. Atypical lab findings (consider alternative diagnosis)
      1. AST <50 U/L (<0.83 ukat/L)
      2. AST/ALT <1.5
      3. AST or ALT >400 U/L (>6.68 ukat/L)
    6. Autoimmune liver disease findings
      1. Antinuclear Antibody >1:160
      2. Anti-Smooth Muscle Antibody >1:80
    7. Other confounding and comorbid conditions
      1. Viral Hepatitis
      2. Biliary obstruction
  3. Confirmatory Testing
    1. See Fibrosis Probability Score
    2. See Cirrhosis for Noninvasive Staging of Hepatic Fibrosis
    3. Liver biopsy
      1. Indicated if possible confounding factor diagnosis would alter management
      2. Noninvasive measures are preferred in other cases
      3. Arab (2021) Clin Liver Dis 25(3):571-84 +PMID:34229840 [PubMed]
  4. References
    1. Crabb (2020) Hepatology 71(1):306-33 +PMID: 31314133 [PubMed]

XI. Management: General Measures

  1. See Prevention of Liver Disease Progression
  2. Alcohol Cessation
    1. See Alcoholism Management
    2. See Alcohol Withdrawal Protocol
  3. Nutritional Management
    1. Increased caloric and Protein intake
    2. Vitamin Supplementation
      1. Thiamine
      2. Folate
      3. Multivitamin
  4. Manage comorbidities
    1. Treat acute infections
      1. Consider empiric broad spectrum Antibiotics until cultures are negative
      2. High Incidence of comorbid acute infection in Alcoholic Hepatitis

XII. Management: Severe Alcoholic Hepatitis

  1. Indications
    1. Maddrey Discriminant Function Score >= 32 or
    2. MELD Score >=21
  2. Precautions
    1. Management below assumes that any acute infections have been fully treated and resolved
  3. Corticosteroids (Prednisolone)
    1. Efficacy: Improves survival (n=61)
      1. Two month survival 88% versus 45% with Placebo
      2. Improved survival persists for 1 year
      3. No advantage after 1 year
    2. References
      1. Mathurin (1996) Gastroenterology 110:1847-53 [PubMed]
    3. Protocol
      1. Avoid Corticosteroids until acute infections are excluded (including negative cultures)
      2. Start Corticosteroids
        1. Prednisolone 40 mg orally daily or
        2. Methylprednisolone 32 mg IV daily
      3. Reevaluate for Corticosteroid responsiveness at 7 days with Lille Score
        1. https://www.mdcalc.com/lille-model-alcoholic-hepatitis
        2. Lille Score >0.45: Failed Corticosteroid trial
          1. Stop Corticosteroids
          2. Refer for early Liver Transplant (see below)
        3. Lille Score <0.45: Corticosteroid Responsive
          1. Complete 28 day course of Corticosteroids, then taper off
  4. Liver Transplant Indications
    1. MELD Score >=21
    2. Spontaneous Bacterial Peritonitis episode
    3. Comorbid Hepatocellular Carcinoma
    4. Alcohol associated liver disease
      1. No improvement after 3 months of abstaining from Alcohol
      2. Child-Pugh Class C (10 to 15)
    5. New onset of decompensated liver disease
      1. Hepatic Ascites
      2. Hepatic Encephalopathy
      3. Jaundice
      4. Bleeding Esophageal Varices

XIII. Complications

  1. Infection
    1. Spontaneous Bacterial Peritonitis
    2. Urinary Tract Infection
    3. Pneumonia
    4. Enterocolitis
    5. Cellulitis
  2. Chronic comorbidities
    1. Cirrhosis
    2. Hepatocellular Carcinoma
    3. Esophageal Varices (Portal Hypertension)
    4. Hepatic Ascites
    5. Esophageal Varices
    6. Hepatorenal Syndrome

XIV. Prognosis

  1. Acute Alcoholic Hepatitis
    1. Maddrey Discriminant Function predicts patients at highest risk of death
    2. Severe Alcoholic Hepatitis mortality 16 to 30% at 28 days (56% at one year)
  2. Chronic Alcholic Hepatitis
    1. Cirrhosis develops in 20% of patients with chronic heavy Alcohol use
    2. Cirrhosis develops in 50% of chronic Alcoholic Hepatitis patients
    3. Additional Cirrhosis risks
      1. Genetic predisposition
      2. Tobacco Abuse (1 ppd, RR 3)
      3. MASLD Risks (e.g. Obesity, Diabetes Mellitus)

XV. Prevention

  1. See Alcohol Use Disorder
  2. See Alcohol Abuse Screening
  3. See Alcohol Abuse Management

XVI. References

  1. Hill (1998) Postgrad Med 103(4):261-275 [PubMed]
  2. Keating (2022) Am Fam Physician 105(4): 412-20 [PubMed]
  3. Jophlin (2024) Am J Gastroenterol 119(1): 30-54 [PubMed]

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