212.1 🎓 醫孞生版

212.1.0.1 📌 䞀頁重點

  • Virus: ssRNA Picornaviridae (Hepatovirus genus)
  • Transmission: fecal-oral primarily; contaminated food/water; person-to-person; rare blood
  • Reservoir: humans only
  • Incubation: 15-50 days (mean 28)
  • Clinical:
    • Mild URI-like prodrome (1-2 wk): fever, malaise, anorexia, nausea, abdominal pain
    • Icteric phase: jaundice, hepatomegaly, dark urine, light stool, pruritus (2-4 wk)
    • Never chronic — key feature distinguishing HAV from HBV/HCV
    • Severe: fulminant hepatic failure (1-2% adults — much higher in older)
    • Cholestatic variant — prolonged jaundice + itching
    • Relapsing variant — recurrent symptoms over months
  • Mortality: ~ 0.3% overall; up to 2-3% in ≥ 50 yr; fulminant rare but possible
  • Diagnosis:
    • IgM anti-HAV = acute infection
    • IgG anti-HAV = past infection or vaccination (immunity)
    • PCR (research / outbreak surveillance)
    • Liver enzymes elevated (AST/ALT often 1000+)
  • Treatment: supportive only; liver transplant for fulminant
  • Prevention:
    • Vaccine (inactivated): 2-dose series 6-12 mo apart
    • Universal childhood vaccination in many countries (USA 2006, Taiwan)
    • Pre-exposure prophylaxis: high-risk travelers, MSM, IDU, food handlers
    • Post-exposure prophylaxis: vaccine ± immunoglobulin within 14 days
  • 2017-2024 USA outbreaks: homeless + IDU + MSM clusters in CA, KY, TN, MI; reactivation of HAV transmission in urban settings; vaccination campaigns

212.1.0.2 1⃣ Virology

  • ssRNA picornavirus
  • Hepatovirus genus
  • Single serotype (despite genotype variation)
  • Capsid VP1-VP4
  • Acid + heat stable (survives stomach + persists environment)
212.1.0.2.1 Pathogenesis
  • Ingestion → gut absorption → portal blood → hepatocytes
  • Replication in hepatocytes
  • Cytopathic + immune-mediated hepatocellular damage
  • Viral shedding in bile + feces (begins 1-2 wk before symptoms; peak just before icterus; declines after)
  • IgM rise → IgG seroconversion
  • Lifelong immunity after natural infection or vaccination

212.1.0.3 2⃣ Epidemiology

212.1.0.3.1 Global Distribution
  • High endemicity: low-income countries (universal childhood acquisition)
  • Intermediate: middle-income, transitioning
  • Low: developed countries (now adolescent + adult susceptibility increasing)
212.1.0.3.2 Transmission Routes
  • Fecal-oral primary
  • Food: contaminated water, shellfish (filter-feeders concentrate virus), produce (irrigated with contaminated water)
  • Person-to-person: close contact (households, daycare)
  • Sexual: MSM (anal-oral)
  • Blood: rare (transient viremia; not chronic carrier state)
  • Vertical: rare
212.1.0.3.3 Risk Groups
  • International travelers to endemic
  • MSM
  • IDU
  • Homeless (recent USA outbreaks)
  • Food handlers (transmission)
  • Childcare workers
  • Chronic liver disease (severe disease if infected)
212.1.0.3.4 2017-2024 USA Outbreaks
  • CA 2017+ homeless + IDU outbreak (San Diego)
  • KY, TN, MI, FL clusters since 2018
  • 40,000+ cases since 2016
  • Hospitalization rate ~ 60%
  • Deaths reported
  • Drivers: housing instability, drug use, vaccination gaps, sanitation in homeless settings
  • Public Health response: mass vaccination, sanitation, harm reduction

212.1.0.4 3⃣ Clinical

212.1.0.4.1 Incubation (15-50 d)
  • Asymptomatic during incubation
  • Shedding begins 1-2 wk before symptoms
212.1.0.4.2 Prodromal Phase (1-2 wk)
  • Fever
  • Malaise, fatigue
  • Anorexia
  • Nausea, vomiting
  • RUQ pain
  • Mild URI-like
  • Aversion to smoke / tobacco (classic clue)
212.1.0.4.3 Icteric Phase (2-4 wk)
  • Jaundice + pruritus
  • Dark urine (bilirubin) + clay-colored stool
  • Hepatomegaly + tender
  • Splenomegaly (10-20%)
  • Symptoms paradoxically improve as bilirubin rises
  • Liver enzymes peak (AST/ALT > 1000 common)
212.1.0.4.4 Recovery Phase
  • 4-8 wk total disease duration usually
  • Complete recovery in most
  • Lifelong immunity
212.1.0.4.5 Severe / Atypical Forms
212.1.0.4.5.1 Fulminant Hepatic Failure
  • 1-2% adults; higher in older (≥ 50 yr 2-5%)
  • Encephalopathy, coagulopathy, hypoglycemia
  • INR > 1.5
  • Hepatic encephalopathy onset within 8 wk of symptoms
  • Mortality 60-80% without liver transplant
  • King’s College criteria for transplant referral
212.1.0.4.5.2 Cholestatic Hepatitis
  • Prolonged jaundice (months)
  • Pruritus prominent
  • Self-limited eventually
212.1.0.4.5.3 Relapsing Hepatitis
  • Recurrent symptoms over 6-12 months
  • Self-limited
  • Not chronic infection
212.1.0.4.5.4 Autoimmune-like Sequelae
  • Rare cases of autoimmune hepatitis post-HAV

212.1.0.5 4⃣ Diagnosis

212.1.0.5.1 Serology
  • IgM anti-HAV — acute infection (positive at symptom onset, persists 3-6 months)
  • IgG anti-HAV — past infection or vaccination (lifelong)
212.1.0.5.2 Liver Enzymes
  • AST/ALT 1000-5000 typical (very high)
  • Bilirubin variable
  • ALP mildly elevated (cholestatic variant higher)
  • PT/INR — assess severity (prolonged = severe/fulminant)
  • Albumin (severe)
  • Glucose (severe — hypoglycemia)
212.1.0.5.3 Imaging
  • Not routinely needed
  • Ultrasound for differentiation (rule out obstruction)
212.1.0.5.4 Other Tests
  • HBV serology (concurrent test)
  • HCV serology
  • HEV serology (acute hepatitis differential)
  • Differential: drug-induced, autoimmune, HSV (rare hepatitis), CMV, EBV mononucleosis, leptospirosis, malaria

212.1.0.6 5⃣ Treatment

212.1.0.6.1 Supportive
  • Hydration, rest, antiemetic, antipruritic
  • Avoid hepatotoxic medications (acetaminophen safe in low doses if liver function OK)
  • Avoid alcohol
  • Adequate nutrition
212.1.0.6.2 Hospitalization
  • Severe symptoms
  • Inability to maintain hydration
  • Coagulopathy (INR > 1.5)
  • Mental status changes
  • Pregnancy 3rd trimester
  • Older + comorbid
212.1.0.6.3 Fulminant
  • ICU
  • Mannitol for cerebral edema
  • N-acetylcysteine (some evidence)
  • Liver transplant if King’s College criteria met
  • Coagulopathy management

212.1.0.7 6⃣ Prevention

212.1.0.7.1 Vaccine
  • Inactivated (HAVRIX, VAQTA)
  • 2-dose series 6-12 mo apart
  • > 95% efficacy seroconversion
  • Lifelong immunity expected (long-term Ab data 25+ yr)
212.1.0.7.2 Recommendations (ACIP 2024)
  • Universal childhood vaccination 12-23 mo (USA 2006)
  • Catch-up children + adolescents through 18 yr if not vaccinated
  • Adults at risk:
    • International travelers (endemic regions)
    • MSM
    • IDU
    • Chronic liver disease (HBV, HCV, cirrhosis)
    • Healthcare workers (some exposures)
    • Childcare / institutional
    • Food handlers (where required)
    • Pregnancy: safe if needed (inactivated)
  • Outbreak vaccination: homeless populations, IDU, MSM in outbreak settings
212.1.0.7.3 Twinrix (HAV + HBV Combination)
  • Used for travel + high-risk
  • 3-dose series
212.1.0.7.4 Post-Exposure Prophylaxis (PEP)
  • Within 14 days of exposure
  • Vaccine if previously unvaccinated:
    • Healthy 1-40 yr: vaccine alone
    • + Immunoglobulin if < 12 mo, > 40 yr, immunocompromise, chronic liver disease
  • Household + sexual + daycare + childcare close contacts
212.1.0.7.5 Sanitation + Hygiene
  • Handwashing
  • Safe food + water (high-risk travelers)
  • Avoid raw / undercooked shellfish (filter-feeders)
  • Cook shellfish thoroughly (heat inactivates HAV)
  • Don’t eat from street food (where uncertain)