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Hepatitis C Treatment Obsidian Format

[!info]+ Treatment of Hepatitis C: An Evolving Success Story Hepatitis C virus (HCV) is a global cause of chronic liver disease, cirrhosis, HCC, and transplantation.
- 58 million chronically infected, 1.5 million new cases/year (WHO).
- Interferon-based therapies had low cure rates + high toxicity.
- Now: DAAs → >95% SVR, 8–12 week oral regimens, minimal side effects.

[!tip]+ 1. Goals of Therapy - Primary goal: Achieve SVR-12 (undetectable HCV RNA 12 weeks post-treatment).
- Benefits of SVR:
- Halts disease progression
- Reduces extrahepatic complications
- Lowers mortality & transmission
- Secondary goals: QoL, prevent HCC, eliminate HCV by 2030 (WHO).

[!example]+ 2. Evolution of Treatment

2.1 Interferon Era (1991–2011)

  • Peg-IFN + Ribavirin
  • SVR: 40–50% (GT1), up to 80% (GT2/3)
  • Drawbacks: 24–48 week injections, flu-like symptoms, cytopenias, depression

2.2 Triple Therapy (2011–2013)

  • Telaprevir/Boceprevir + Peg-IFN/RBV
  • Slight SVR improvement, increased toxicity & interactions

2.3 DAA Era (2013–present)

  • Sofosbuvir revolutionized care
  • Pan-genotypic DAA combos: cure all genotypes, high tolerability, short course

[!abstract]+ 3. Mechanisms of DAAs - Target 3 non-structural proteins:
- NS3/4A Protease inhibitors → glecaprevir, grazoprevir
- NS5A Inhibitors → ledipasvir, pibrentasvir, velpatasvir
- NS5B Polymerase inhibitors:
- Nucleotide: sofosbuvir
- Non-nucleotide: dasabuvir

[!check]+ 4. Current Guideline-Recommended Regimens

4.1 First-Line Regimens (Compensated Disease)

  • Glecaprevir/Pibrentasvir – 8 weeks (12 if cirrhotic)
  • Sofosbuvir/Velpatasvir – 12 weeks
  • Sofosbuvir/Velpatasvir/Voxilaprevir – for prior DAA failures

4.2 Special Scenarios

  • Decompensated cirrhosis: Sofosbuvir/Velpatasvir ± RBV for 12–24 weeks
  • eGFR <30 mL/min or dialysis: Glecaprevir/Pibrentasvir
  • Pediatrics:
  • Sofosbuvir/Velpatasvir ≥3 yrs
  • Glecaprevir/Pibrentasvir ≥12 yrs
  • Post-transplant: Adjust for drug–drug interactions

[!question]+ 5. Practical Considerations in DAA Use

5.1 Baseline

  • Confirm chronic HCV ± genotype
  • Fibrosis staging: elastography or non-invasive scores
  • HBV screening
  • Evaluate renal function, pregnancy, drug interactions

5.2 On-Treatment

  • VL at week 4 and 12 weeks post-treatment
  • Safety labs only if decompensated or RBV used

5.3 Adverse Effects

  • DAAs: Headache, fatigue, nausea <15%
  • RBV: Hemolytic anemia, teratogenic → monitor closely

[!quote]+ 6. Special Populations and Coinfections

6.1 HIV/HCV Coinfection

  • DAAs are effective
  • ART optimization prevents drug interactions

6.2 Pregnancy

  • No approved DAA yet; data on SOF/VEL promising
  • Ribavirin is teratogenic

6.3 Active Substance Use

  • Treat PWID + harm reduction (NSP, OAT)
  • Essential for elimination strategy

[!caution]+ 7. Real-World Barriers

7.1 Diagnostics & Linkage

  • Many remain undiagnosed
  • Screening (18–79 yrs) & reflex RNA testing improving detection

7.2 Cost & Access

  • LMICs: <US$100/course
  • High-income countries: >US$20,000/course → coverage barriers

7.3 Reinfection

  • PWID, MSM at higher risk
  • Require behavioral + biomedical prevention strategies

[!future]+ 8. Future Directions

8.1 Simplified Models

  • Shorter regimens (≤6 weeks), no genotype testing

8.2 Long-Acting Injectables

  • Subcutaneous/implantable antivirals for adherence

8.3 Vaccine Development

  • Early-phase trials underway
  • Would complement DAA therapy in elimination goals

8.4 Biomarker Surveillance

  • SVR ≠ zero HCC risk in cirrhotics
  • Tools like GALAD score, advanced imaging needed

[!summary]+ Conclusion The HCV treatment journey has evolved from interferon-based struggle to DAA-driven success.
- DAAs: Cure rates >95%, short duration, excellent tolerability
- Remaining gaps: screening, access, reinfection, real-world implementation
- With sustained global effort, HCV can shift from a public threat to a vanquished virus by 2030.