355.1 🎓 醫孞生版

355.1.0.1 📌 䞀頁重點

355.1.0.1.1 Hepatitis A Virus (HAV)
355.1.0.1.1.1 Characteristics
  • Picornavirus, ssRNA
  • Fecal-oral transmission
  • Contaminated food / water
  • Travel-associated
  • Endemic in developing countries
355.1.0.1.1.2 Clinical
  • Incubation 15-50 days
  • Acute self-limited illness (1-4 weeks)
  • Children often asymptomatic
  • Adults more symptomatic
  • Anicteric → icteric → recovery
  • No chronic infection
  • Rare fulminant hepatitis (especially adults > 50)
355.1.0.1.1.3 Diagnosis
  • Anti-HAV IgM (acute)
  • Anti-HAV IgG (immunity / past infection)
  • Vaccination: anti-HAV total positive
355.1.0.1.1.4 Treatment
  • Supportive
  • Prevention: HAV vaccine (2-dose series)
  • Post-exposure prophylaxis: vaccine ± immune globulin
355.1.0.1.1.5 Vaccination
  • HAV inactivated vaccine
  • 2 doses 6-12 months apart
  • ≥ 95% efficacy
  • Lifelong immunity
  • Recommended for: travelers, men sex with men, IDU, chronic liver disease, food handlers, occupational risk
355.1.0.1.2 Hepatitis B Virus (HBV)
355.1.0.1.2.1 Characteristics
  • Hepadnavirus, partial double-stranded DNA
  • Parenteral, sexual, perinatal transmission
  • Worldwide; high prevalence Asia, Africa
  • Taiwan historically high prevalence (15%+ pre-vaccine)
  • Universal vaccination since 1986 reduced dramatically
355.1.0.1.2.2 Transmission
  • Blood, body fluids
  • Sexual
  • Perinatal (most common in endemic areas — high transmission rate ~ 90%)
  • Healthcare workers
  • IDU
  • Sexual partners
355.1.0.1.2.3 Phases of Chronic HBV

Immune Tolerant: - HBeAg positive - High HBV DNA - Normal ALT - Minimal liver damage - Common in perinatally acquired (young adults Asian)

Immune Active (HBeAg Positive Chronic Hepatitis): - HBeAg positive - High HBV DNA - Elevated ALT - Active liver damage - Treatment indicated

Immune Active (HBeAg Negative Chronic Hepatitis): - HBeAg negative - Variable HBV DNA (often fluctuating) - Elevated ALT - Active liver damage - Treatment indicated

Inactive Carrier: - HBeAg negative - Low HBV DNA (< 2000 IU/mL) - Normal ALT - Minimal liver damage - Monitor, may not need treatment

HBsAg Loss / Functional Cure: - HBsAg negative - Anti-HBs positive - Excellent prognosis

355.1.0.1.2.4 Serology Patterns
Marker Acute Window Resolved Chronic Vaccinated
HBsAg + - - + -
Anti-HBs - - + - +
Anti-HBc total + + + + -
Anti-HBc IgM + + - - -
HBeAg + - - ± -
HBV DNA + ± - ± -
355.1.0.1.2.5 Clinical Course
  • Incubation 6 weeks-6 months
  • Acute: fatigue, nausea, jaundice, RUQ pain
  • Most adults recover (95%)
  • Chronic HBV:
    • 5-10% of adult infections
    • 30% of childhood infections
    • 90% of perinatal infections
  • Cirrhosis (15-25% over decades)
  • HCC (3-8x risk)
355.1.0.1.2.6 Diagnosis
  • HBsAg + anti-HBc IgM: acute
  • HBsAg ≥ 6 months: chronic
  • HBV DNA quantification
  • HBeAg + anti-HBe (phase)
  • ALT, FibroScan, MR elastography
  • US for HCC surveillance (every 6 months)
  • AFP (HCC marker)
  • Liver biopsy selected
355.1.0.1.2.7 Treatment

Indications: - HBeAg+: HBV DNA > 20,000 + ALT > 2x ULN - HBeAg-: HBV DNA > 2,000 + ALT > ULN - Cirrhosis with detectable DNA - Pregnancy with high viral load (prevent vertical transmission) - Immunosuppression / chemotherapy (prophylaxis)

First-Line Antivirals: - Entecavir (Baraclude): high barrier to resistance; oral once daily; cheap generic - Tenofovir disoproxil fumarate (TDF, Viread): kidney + bone effects; old standard - Tenofovir alafenamide (TAF, Vemlidy): less kidney + bone toxicity; newer - All suppress HBV DNA + improve ALT + slow progression - Long-term therapy typically (often lifelong)

Older / Less Used: - Lamivudine, telbivudine, adefovir: resistance issues; limited use now

PEG-Interferon: - Younger non-cirrhotic - Finite course (48 weeks) - ~ 30% achieve HBeAg seroconversion - Higher chance of HBsAg loss (~ 5-10%) - Many side effects

355.1.0.1.2.8 Functional Cure / Discontinuation
  • HBsAg loss = functional cure
  • Rare with standard NA monotherapy
  • New therapies emerging:
    • Bepirovirsen (siRNA): trials promising
    • Capsid inhibitors: phase 2/3
    • Therapeutic vaccines
  • Goal: durable HBsAg loss
355.1.0.1.2.9 HCC Surveillance
  • For all chronic HBV (regardless of cirrhosis if Asian male > 40 / female > 50, family hx HCC)
  • Ultrasound every 6 months ± AFP
  • Earlier in high-risk groups
355.1.0.1.2.10 Vaccination
  • HBV vaccine (3-dose series at 0, 1, 6 months)
  • ≥ 95% efficacy
  • Universal in newborns + at-risk
  • Boosters generally not needed
  • Anti-HBs ≥ 10 mIU/mL = immune
355.1.0.1.3 Hepatitis C Virus (HCV)
355.1.0.1.3.1 Characteristics
  • Flavivirus, ssRNA
  • 6 genotypes (1-6); subtypes (1a, 1b, etc.)
  • Parenteral transmission
  • Sexual + perinatal much less than HBV
  • IDU + blood transfusion (pre-1992) main routes
  • ~ 70 million globally infected
355.1.0.1.3.2 Clinical Course
  • Incubation 6-7 weeks
  • Acute: mild, often asymptomatic
  • Chronic in 75-85% (high)
  • Slow progression (decades)
  • Cirrhosis (15-25% in 20 yr)
  • HCC, decompensation
355.1.0.1.3.3 Diagnosis
  • Anti-HCV antibody (screening)
  • HCV RNA (confirmation + viral load)
  • HCV genotype (less critical with pan-genotypic DAAs)
  • Liver fibrosis assessment
355.1.0.1.3.4 Treatment — DAAs (Direct-Acting Antivirals)

Revolution Since 2014: - Cure rates > 95% - 8-12 weeks oral - Well-tolerated - All HCV patients should be treated (USPSTF Class A)

Pan-Genotypic Regimens (Most Common): - Sofosbuvir + velpatasvir (Epclusa) — 12 weeks - Glecaprevir + pibrentasvir (Mavyret) — 8 weeks (treatment-naive non-cirrhotic) - Sofosbuvir + velpatasvir + voxilaprevir (Vosevi) — for treatment-experienced

Cirrhotic Patients: - Compensated: same regimens, sometimes 12 weeks - Decompensated: avoid protease inhibitors (use sofosbuvir + velpatasvir or sofosbuvir + daclatasvir)

Common DAAs by Mechanism: - NS3/4A protease inhibitors: grazoprevir, glecaprevir, voxilaprevir - NS5A inhibitors: ledipasvir, velpatasvir, pibrentasvir, elbasvir - NS5B polymerase inhibitors: sofosbuvir

Side Effects: - Generally well-tolerated - Headache, fatigue, nausea - Drug interactions (especially amiodarone with sofosbuvir → bradycardia) - HBV reactivation (screen HBsAg, anti-HBc before; prophylaxis if positive)

355.1.0.1.3.5 Post-Treatment
  • SVR (sustained virologic response) at 12 weeks post-treatment = cure
  • Fibrosis may improve
  • HCC surveillance continues for cirrhotic
  • Reinfection possible (risk reduction)
355.1.0.1.3.6 Vaccination
  • No HCV vaccine
  • Hepatitis A + B vaccines for HCV-infected
355.1.0.1.4 Hepatitis D Virus (HDV / Delta)
355.1.0.1.4.1 Characteristics
  • Defective RNA virus (deltavirus)
  • Requires HBV (HBsAg) for replication
  • Worldwide; high in Mediterranean, Middle East, Central Africa, South America
  • ~ 5% of HBV co-infected globally
355.1.0.1.4.2 Transmission
  • Same as HBV
  • IDU + sexual
355.1.0.1.4.3 Clinical Course
  • Co-infection (HBV + HDV simultaneously):
    • Acute hepatitis usually self-limited
    • Severe sometimes
  • Superinfection (HDV on chronic HBV):
    • More severe acute hepatitis
    • Higher rate of fulminant hepatitis (10%)
    • Often chronic — accelerated cirrhosis + HCC
355.1.0.1.4.4 Diagnosis
  • Anti-HDV antibody
  • HDV RNA
  • All HBV patients should be tested for HDV
355.1.0.1.4.5 Treatment
  • PEG-interferon-α (older, limited efficacy)
  • Bulevirtide (Hepcludex) — entry inhibitor; FDA approval 2023; subcutaneous daily
355.1.0.1.5 Hepatitis E Virus (HEV)
355.1.0.1.5.1 Characteristics
  • Hepevirus, ssRNA
  • 4 genotypes (1-4)
  • Fecal-oral transmission
  • Genotypes 1, 2: water-borne, developing countries
  • Genotypes 3, 4: zoonotic (pigs, deer, shellfish), developed countries
355.1.0.1.5.2 Clinical
  • Incubation 15-60 days
  • Acute self-limited
  • Severe in pregnancy (10-25% mortality in 3rd trimester!)
  • Chronic in immunocompromised (organ transplant, HIV, hematologic malignancy)
  • Neurologic, renal manifestations rarely
355.1.0.1.5.3 Diagnosis
  • Anti-HEV IgM (acute)
  • HEV RNA (chronic, confirmation)
355.1.0.1.5.4 Treatment
  • Supportive (acute)
  • Chronic HEV:
    • Ribavirin × 3 months (most effective)
    • PEG-IFN (selected)
    • Reduce immunosuppression
  • Pregnancy: supportive; no specific antiviral safe
355.1.0.1.5.5 Vaccination
  • Available in China (HEV 239)
  • Limited global availability
355.1.0.1.6 Approach to Acute Viral Hepatitis

355.1.1 Initial Evaluation

  • History: exposures, travel, IDU, transfusions, sexual, occupation, family
  • Symptoms: fatigue, nausea, jaundice, RUQ pain
  • Exam: hepatomegaly, jaundice, stigmata of chronic liver disease
  • Labs: ALT/AST elevation, bilirubin, PT/INR, albumin
  • Viral serologies

355.1.2 Differential

  • Hep A, B (acute or flare), C (rare acute presentation), D, E
  • Drug-induced hepatitis
  • Autoimmune hepatitis
  • Ischemic hepatitis
  • Wilson disease
  • Toxin
  • HSV (immunocompromised)

355.1.3 Management

  • Supportive
  • Avoid alcohol + hepatotoxins
  • Hospitalize if severe (high INR, mental status, severe dehydration)
  • ALF workup if appropriate (Ch360)
355.1.3.0.1 Approach to Chronic Viral Hepatitis

355.1.4 Screening

  • HBsAg + anti-HCV for high-risk + universal recommended
  • USPSTF Class B: HCV all adults (and pregnant)
  • USPSTF: HBV in pregnancy + high-risk

355.1.5 Workup

  • Full viral panel
  • Liver fibrosis assessment (FibroScan, ELF, FIB-4)
  • Imaging
  • HCC surveillance plan
  • Vaccinations (HAV, HBV if susceptible)
  • Risk factor counseling

355.1.6 Decision to Treat

  • Based on stage + activity + indication
  • All HCV patients should be treated
  • HBV per criteria (above)

355.1.6.1 🩺 床邊速查

  • HAV: fecal-oral, self-limited, no chronic; vaccine available
  • HBV: parenteral/sexual/perinatal; chronic in 5% adult / 30% child / 90% perinatal; entecavir or tenofovir
  • HCV: parenteral mainly; chronic 75-85%; DAAs cure > 95% (Epclusa, Mavyret)
  • HDV: requires HBV; bulevirtide FDA 2023
  • HEV: fecal-oral; severe in pregnancy; ribavirin for chronic
  • HCC surveillance: chronic HBV (Asian male > 40 / female > 50, family hx, cirrhotic) — US ± AFP every 6 mo
  • HBV reactivation: screen + prophylaxis before chemo / IS