355.3 🏥 內科專科考前版

355.3.1 Mechanistic Deep Dive

355.3.1.1 HBV Replication

  • Reverse transcription (despite DNA virus)
  • cccDNA persists in hepatocyte nuclei → reservoir
  • Difficult to eradicate
  • Functional cure (HBsAg loss) goal

355.3.1.2 HCV Genome

  • Translated as polyprotein
  • Cleaved by host + viral proteases
  • NS3/4A protease, NS5A, NS5B polymerase
  • All DAA targets

355.3.1.3 HDV Replication

  • Uses HBsAg envelope
  • Hepatocyte-specific
  • Bulevirtide blocks NTCP entry

355.3.2 Recent Trials & Updates

355.3.2.1 Bepirovirsen (siRNA for HBV)

  • ASO targeting HBsAg
  • B-Clear (2023): some HBsAg loss
  • Trials ongoing

355.3.2.2 Vebicorvir (HBV Capsid Inhibitor)

  • Phase 2/3

355.3.2.3 Bulevirtide for HDV

  • MYR301 trial
  • FDA 2023

355.3.2.4 HCV Post-DAA Era

  • Reinfection risk
  • Continued surveillance
  • HCC risk persists

355.3.2.5 USPSTF HCV Recommendations

  • All adults 18-79 universal screening (Class B 2020)
  • Pregnant women

355.3.3 High-Yield Specialist Points

355.3.3.1 HBV Reactivation Prophylaxis

  • Pre-treatment screening
  • Rituximab: highest risk
  • Other chemotherapy: high
  • TNF inhibitors: moderate
  • Steroids long-term: variable
  • Prophylactic antiviral (entecavir or tenofovir)

355.3.3.2 HBV Treatment Discontinuation

  • HBeAg+: after seroconversion + 12 months consolidation
  • HBeAg-: longer treatment
  • Cirrhosis: typically lifelong
  • HBsAg loss: rare but durable

355.3.3.3 HBV in Pregnancy

  • TDF preferred (safety data)
  • Continue through delivery
  • Vertical transmission prevention

355.3.3.4 HCV in Pregnancy

  • Avoid DAAs (limited safety data)
  • Treat after delivery
  • Vertical transmission rare (5-10%)
  • No specific intervention

355.3.3.5 HCV Genotype Considerations

  • Pan-genotypic regimens make less important
  • Some still use for specific cases
  • Genotype 3 historically more difficult

355.3.3.6 DAA Drug Interactions

  • Amiodarone + sofosbuvir: bradycardia
  • St. John’s wort: ↓ levels
  • Anticonvulsants: ↓ levels
  • Statins: avoid simvastatin/lovastatin
  • AIDS antiretrovirals: check

355.3.3.7 HEV Chronic in Transplant

  • Up to 50% become chronic
  • Genotype 3 mainly
  • Ribavirin × 3 months (60-80% cure)
  • Reduce immunosuppression if possible

355.3.3.8 Acute HBV Infection

  • 95% adults clear
  • Treatment usually not required
  • Supportive
  • Acute liver failure: liver transplant evaluation

355.3.3.9 HBV Vaccine Non-Responders

  • 5-10%
  • Booster dose
  • Switch to different vaccine
  • Re-test antibody
  • Use HBIG for high-risk exposure

355.3.3.10 Hep B Surface Antibody (Anti-HBs)

  • Quantitative measurement
  • ≥ 10 mIU/mL = immune
  • Vaccine-derived only: anti-HBs + (anti-HBc -)
  • Naturally acquired immunity: anti-HBs + anti-HBc total

355.3.4 Pearls

  • HAV + HEV: fecal-oral, no chronic except HEV in IS
  • HBV: parenteral, perinatal; chronic in 5% adult, 90% perinatal
  • HCV: parenteral; chronic 75-85%; DAAs cure > 95%
  • HDV: requires HBV; bulevirtide FDA 2023
  • HEV pregnancy 3rd trimester: 10-25% mortality
  • HCC surveillance: US ± AFP every 6 mo for chronic HBV + cirrhotic
  • HBV reactivation: screen before chemo/IS + prophylaxis if positive
  • DAA + HBV: screen for reactivation before treatment