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. Prolonged INR (or ProTime)
    2. Alkaline Phosphatase elevated
    3. Gamma Glutamyl Transferase (GGT) markedly elevated
    4. Hypoalbuminemia (decreased Serum Albumin and Serum Prealbumin)
    5. 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. 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. Esophageal Varices (Portal Hypertension)
    2. Hepatic Ascites
    3. Esophageal Varices
    4. 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 50% of chronic Alcoholic Hepatitis patients

XV. References

  1. Hill (1998) Postgrad Med 103(4):261-275 [PubMed]
  2. Keating (2022) Am Fam Physician 105(4): 412-20 [PubMed]

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Related Studies

Ontology: Acute alcoholic liver disease (C0001306)

Concepts Disease or Syndrome (T047)
ICD9 571.1
SnomedCT 155810001, 9953008
Dutch acute alcoholische hepatitis, acuut; hepatitis, alcoholisch, hepatitis; acuut, alcoholisch
French Hépatite alcoolique aiguë
German akute alkoholische Hepatitis
Italian Epatite acuta alcolica
Portuguese Hepatite alcoólica aguda
Spanish Hepatitis aguda alcohólica, daño hepático agudo por alcohol, hepatitis alcohólica aguda (trastorno), hepatitis alcohólica aguda
Japanese 急性アルコール性肝炎, ｷｭｳｾｲｱﾙｺｰﾙｾｲｶﾝｴﾝ
Czech Akutní alkoholická hepatitida
English Ac alcoholic hepatitis, acute alcoholic hepatitis, Acute alcoholic hepatitis (disorder), Acute alcoholic hepatitis, Acute alcoholic liver disease, Acute alcoholic liver disease (disorder), hepatitis; acute, alcoholic, acute; hepatitis, alcoholic, Acute Alcoholic Hepatitis
Hungarian Acut alkoholos hepatitis
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Hepatitis, Alcoholic (C0019187)

Definition (MSH) INFLAMMATION of the LIVER due to ALCOHOL ABUSE. It is characterized by NECROSIS of HEPATOCYTES, infiltration by NEUTROPHILS, and deposit of MALLORY BODIES. Depending on its severity, the inflammatory lesion may be reversible or progress to LIVER CIRRHOSIS.
Definition (MSHCZE) Jaterní poškození způsobené alkoholem, zejm. excesem v rámci dlouhodobého alkoholismu; další prognózu výrazně ovlivňuje další konzumace alkoholu či úplná abstinence. Kromě známek zánětu bývá i steatóza.(cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (CSP) acute or chronic degenerative and inflammatory lesion of the liver in the alcoholic which is potentially progressive though sometimes reversible; it does not necessarily include steatosis, fibrosis, or cirrhosis of the liver, although it is frequently associated with these conditions; it is characterized by liver cell necrosis, infiltration by polymorphonuclear leukocytes and lymphocytes, and Mallory bodies.
Concepts Disease or Syndrome (T047)
MSH D006519
ICD10 K70.1
SnomedCT 197312006, 235875008
English Alcoholic Hepatitis, Hepatitis, Alcoholic, alcoholic hepatitis (diagnosis), alcoholic hepatitis, Hepatitis alcoholic, Hepatitis, Alcoholic [Disease/Finding], Hepatitis;alcoholic, hepatitis alcohol, alcoholics hepatitis, alcohol hepatitis, hepatitis alcoholic, Alcoholic hepatitis, AH - Alcoholic hepatitis, Alcoholic hepatitis (disorder), ethanol; hepatitis, hepatitis; alcoholic, hepatitis; ethanol, alcohol; hepatitis
Italian Epatite alcoolica, Epatite alcolica
Dutch alcoholische hepatitis, alcohol; hepatitis, ethanol; hepatitis, hepatitis; alcoholisch, hepatitis; ethanol, hepatitis door alcoholgebruik, Alcoholhepatitis, Alcoholische hepatitis, Hepatitis, alcoholische
Swedish Hepatit, alkoholbetingad
Japanese ｱﾙｺｰﾙｾｲｶﾝｴﾝ, アルコール性肝炎, 肝炎-アルコール性
Czech hepatitida alkoholická, Alkoholická hepatitida
Finnish Alkoholimaksatulehdus
Russian ALKOGOL'NYI GEPATIT, GEPATIT ALKOGOL'NYI KHRONICHESKII, GEPATIT ALKOGOL'NYI, АЛКОГОЛЬНЫЙ ГЕПАТИТ, ГЕПАТИТ АЛКОГОЛЬНЫЙ, ГЕПАТИТ АЛКОГОЛЬНЫЙ ХРОНИЧЕСКИЙ
German Alkoholische Hepatitis, Hepatitis alkoholisch, Alkoholhepatitis, Hepatitis, alkoholische
Korean 알코올성 간염
Polish Zapalenie wątroby alkoholowe
Hungarian Alkoholos májgyulladás, Alkoholos hepatitis
Norwegian Alkoholisk hepatitt, Alkoholisk leverbetennelse, Hepatitt, alkoholrelatert, Leverbetennelse, alkoholrelatert
Spanish hepatitis alcohólica (trastorno), hepatitis alcohólica, Hepatitis alcohólica, Hepatitis Alcohólica
Portuguese Hepatite alcoólica, Hepatite Alcoólica
French Hépatite alcoolique, Hépatite éthylique
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Alcoholic Liver Diseases (C0023896)

Definition (MSHCZE) Jaterní onemocnění spojené s ALKOHOLISMEM. Obvykle je deskriptorem odkazováno na výskyt dvou či více alkoholických následků jako je např. ukládání tuku v játrech (STEATÓZA JATER ALKOHOLICKÁ), HEPATITIDA nebo cirhóza (JÁTRA - CIRHÓZA).
Definition (NCI) A disorder caused by damage to the liver parenchyma due to alcohol consumption. It may present with an acute onset or follow a chronic course, leading to cirrhosis.
Definition (MSH) Liver diseases associated with ALCOHOLISM. It usually refers to the coexistence of two or more subentities, i.e., ALCOHOLIC FATTY LIVER; ALCOHOLIC HEPATITIS; and ALCOHOLIC CIRRHOSIS.
Concepts Disease or Syndrome (T047)
MSH D008108
ICD10 K70 , K70.9
SnomedCT 155809006, 266537000, 41309000
English Liver Disease, Alcoholic, Liver Diseases, Alcoholic, Alcoholic liver disease, unspecified, LIVER DIS ALCOHOLIC, ALCOHOLIC LIVER DIS, alcohol induced liver disorder, alcoholic liver disorder, Alcoholic liver disease NOS, Hepatopathy alcoholic, Liver Diseases, Alcoholic [Disease/Finding], alcoholic disease liver, alcoholic diseases liver, alcoholics disease liver, alcoholic liver disease, alcoholic liver diseases, alcoholic liver disease (diagnosis), Alcoholic liver diseases, ALD - Alcoholic liver disease, Alcoholic liver disease, disease (or disorder); liver, alcoholic, liver; alcohol, liver; disease, alcoholic, alcohol; liver, Alcoholic liver disease, NOS, Alcoholic Liver Diseases, Alcoholic Liver Disease
Italian Epatopatia alcoolica, Epatopatia alcoolica NAS, Malattie epatiche alcoliche
Dutch alcoholische hepatopathie, leverziekte door alcoholgebruik NAO, aandoening; lever, bij alcoholgebruik, alcohol; lever, lever; aandoening, bij alcoholgebruik, lever; alcohol, Alcoholische leverziekte, niet gespecificeerd, alcoholische leverziekte, Alcoholische leverziekte, Alcoholische leverziekten, Leverziekte, alcoholische, Leverziekten, alcoholische, Ziekte, lever-, alcoholische
French Hépatopathie alcoolique, Maladie alcoolique du foie SAI, MAF (Maladie Alcoolique du Foie), Maladies hépatiques dues à l'alcool, Maladie alcoolique du foie, Maladie du foie liée à l'alcool, Maladies alcooliques du foie, Maladies hépatiques alcooliques
German alkoholische Lebererkrankung NNB, Lebererkrankung alkoholbedingt, Alkoholische Leberkrankheit, nicht naeher bezeichnet, Alkoholische Leberkrankheit, alkoholische Lebererkrankung, Alkoholische Leberkrankheiten, Leberkrankheiten, alkoholische
Portuguese Hepatopatia alcoólica NE, Hepatopatia alcoólica, Doença hepática associada ao álcool, Hepatopatias Alcoólicas
Spanish Hepatopatía alcohólica NEOM, Hepatopatía alcohólica, hepatopatía alcohólica (trastorno), hepatopatía alcohólica, Enfermedad alcohólica del hígado, Hepatopatías Alcohólicas
Japanese アルコール性肝疾患ＮＯＳ, ｱﾙｺｰﾙｾｲｶﾝｼｯｶﾝNOS, ｱﾙｺｰﾙｾｲｶﾝｼｯｶﾝ, ｱﾙｺｰﾙｾｲｶﾝｼｮｳｶﾞｲ, 肝疾患-アルコール性, アルコール性肝疾患, アルコール性肝障害
Swedish Leversjukdomar, alkoholbetingade
Finnish Alkoholimaksasairaudet
Russian ALKOGOL'NYE BOLEZNI PECHENI, PECHENI BOLEZNI ALKOGOL'NYE, АЛКОГОЛЬНЫЕ БОЛЕЗНИ ПЕЧЕНИ, ПЕЧЕНИ БОЛЕЗНИ АЛКОГОЛЬНЫЕ
Czech Alkoholická hepatopatie, Poškození jater alkoholem, Alkoholická jaterní léze NOS, alkoholické nemoci jater, onemocnění jater způsobená alkoholem, játra - nemoci alkoholické
Korean 상세불명의 알코올성 간질환, 알코올성 간질환
Croatian JETRENE BOLESTI, ALKOHOLNE
Polish Choroby wątroby alkoholowe, Choroby wątroby poalkoholowe
Hungarian Alkoholos májbetegség, Alkoholos májbetegség k.m.n., Hepatopathia alkoholica
Norwegian Leversykdommer, alkoholrelaterte, Alkoholiske leversykdommer
Derived from the NIH UMLS (Unified Medical Language System)

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