II. History

  1. Travel history
  2. Undercooked food ingestion
  3. Hepatotoxin exposure
  4. IV Drug Abuse
  5. Sexually Transmitted Infection risk
  6. Viral Hepatitis exposure

IV. Signs

  1. Dehydration
  2. Jaundice
  3. Hepatomegaly
    1. Firm enlarged, palpable liver edge

V. Labs

  1. See Viral Hepatitis
  2. See Liver Function Test Abnormality
  3. Serum Lipase
  4. Complete Blood Count
  5. Coagulation tests (INR/ProTime, Partial Thromboplastin Time)
    1. INR elevation in the absence of Warfarin is not equivalent to increased bleeding
    2. INR only reflects Factor VII levels, where as liver failure results in both pro and Anticoagulant factors
    3. Consider Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to evaluate Coagulopathy
  6. Direct Bilirubin (Conjugated Bilirubin, fractionated from liver tests)
  7. Serum Ammonia
    1. Indicated if Altered Level of Consciousness
  8. Comprehensive metabolic panel
    1. Electrolytes
    2. Serum Glucose
      1. Hypoglycemia risk
    3. Renal Function tests
    4. Liver Function Tests
      1. Alkaline Phosphatase typically up to twice normal in Viral Hepatitis
      2. Serum Aminotransferases (AST, ALT) up to 10-20 fold above normal in Viral Hepatitis
  9. Viral Hepatitis (consider)
    1. Hepatitis A
      1. xHAV IgM
    2. Hepatitis B
      1. HBsAg
      2. xHBc IgM
    3. Hepatitis C
      1. xHCV Antibody
  10. Toxicology labs (consider)
    1. Urine Toxicology Screening
    2. Blood Alcohol Level
    3. Acetaminophen level
    4. Salicylate level

VII. Differential Diagnosis: Infection

  1. Viral Hepatitis (most common)
    1. Typical acute Viral Hepatitis causes
      1. Hepatitis A
      2. Hepatitis B
      3. Hepatitis C
      4. Hepatitis D
      5. Hepatitis E
    2. Mild Viral Hepatitis causes
      1. Cytomegalovirus (CMV)
      2. Mononucleosis (EBV)
      3. Coxsachievirus
    3. Potentially severe hepatitis (especially in Immunocompromised patients)
      1. Herpes Simplex Virus (HSV)
      2. Varicella
  2. Bacterial hepatitis
    1. Leptospirosis
      1. Associated with animal or tick borne exposure
    2. Q Fever
      1. Relapsing Fever and myalgias
      2. Alkaline Phosphatase significantly increased out of proportion to transaminases
    3. Rocky Mountain Spotted Fever
      1. Jaundice is prominent
    4. Secondary Syphilis
    5. Typhoid Fever
    6. Overwhelming infection (Sepsis)
    7. Liver Abscess (esp. Immunocompromised hosts or those with underlying cancer)
      1. Biliary tract source (Escherichia coli, KlebsiellaPneumoniae)
    8. Fitz-Hugh-Curtis Syndrome
      1. Perihepatic spread of Pelvic Inflammatory Disease
      2. Primarily NeisseriaGonorrhea and Chlamydia trachomatis
  3. Parasite
    1. Entamoeba histolytica
      1. Associated with Liver Abscess
    2. Toxocariasis
      1. Associated with pneumonitis, Leukocytosis with Eosinophil predominance
    3. Liver Trematodes (liver flukes)
  4. Fungal causes
    1. Candida albicans (Liver Abscess)
      1. Seen in Immunocompromised patients especially with prolonged antibiotic exposure

VIII. Differential Diagnosis: Pregnancy related Acute Liver Disease

  1. Hyperemesis Gravidarum
    1. Liver transaminases (AST, ALT) may be over 200 IU/L
    2. Alkaline Phosphatase may be increased up to twice normal
    3. Serum Bilirubin may be increased enough to cause visible Jaundice
  2. HELLP Syndrome
    1. Often associated with Preeclampsia with Severe Hypertension and Proteinuria
    2. Most commonly occurs in third trimester and immediately postpartum
  3. Acute Fatty Liver of Pregnancy
    1. Associated with more severe liver failure and Renal Insufficiency
    2. May be difficult to distinguish with HELLP Syndrome
  4. Intrahepatic Cholestasis of Pregnancy
    1. Most common liver disease in pregnancy (second and third trimester)
    2. Significantly elevated Bilirubin levels risk fetal demise and preterm delivery

IX. Differential Diagnosis: Miscellaneous

  1. Autoimmune Conditions
    1. Systemic Lupus Erythematosus (SLE)
    2. Autoimmune Hepatitis
      1. Women predominate in a bimodal distribution (ages 15 to 25 and 45 to 60 years old)
  2. Medications and drugs
    1. See Hepatotoxin
    2. Alcohol Abuse
    3. Carbon tetrachloride

X. Precautions: Red Flags

  1. Acute Liver Failure - ICU admission criteria
    1. Altered Mental Status
    2. Hypoglycemia
    3. Severe Hyperbilirubinemia
    4. Significant Renal Insufficiency
    5. Significantly abnormal coagulation studies
  2. Viral Hepatitis - hospital admission criteria
    1. Severe Dehydration
    2. Intractable Vomiting
    3. Severe Electrolyte abnormalities
    4. Major comorbid illness
    5. Age 50 years and older
    6. Immunocompromised state

XI. Management

  1. See Fulminant Hepatitis (Acute Liver Failure)
  2. Supportive care
    1. Intravenous rehydration
    2. Antiemetics
  3. Specific management
    1. See Viral Hepatitis
    2. See Acetaminophen Overdose
  4. Disposition
    1. Admit patients with red flag findings (see above) to Intensive Care unit
    2. Most patients may be discharged to home with close interval follow-up with primary care

XII. Prevention

XIII. References

  1. Swaminathan and Weingart in Herbert (2020) EM:Rap 20(10):1-2
  2. Swencki (2015) Crit Dec Emerg Med 29(11):2-10
  3. Swencki (2023) Crit Dec Emerg Med 37(8):4-12
  4. (2004) MMWR Recomm Rep 53(RR-4): 1-33 [PubMed]
  5. Matheny (2012) Am Fam Physician 86(11): 1027-34 [PubMed]

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