Treatment of hepatitis c
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hepatitis C direct acting antivirals treatment regimens
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hepatitis C genotypes treatment duration SVR monitoring
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Treatment of Hepatitis C
Overview
Hepatitis C (HCV) is now a highly curable infection. Modern direct-acting antivirals (DAAs) achieve sustained virologic response (SVR) rates >95%, which is considered a functional cure. Treatment involves simple once-daily oral dosing for 8–16 weeks, with minimal side effects compared to older interferon-based regimens (Harrison's, p. 9520; Treating Hepatitis C, p. 3).
Goals of Treatment
- Achieve SVR12 (undetectable HCV RNA at 12 weeks post-treatment) — equivalent to cure
- Prevent progression to cirrhosis, hepatocellular carcinoma (HCC), and liver failure
- Reduce HCV transmission
Key Drug Classes (DAAs)
| Class | Target | Examples |
|---|---|---|
| NS5B polymerase inhibitors | HCV replication | Sofosbuvir |
| NS5A inhibitors | Viral replication/assembly | Ledipasvir, Velpatasvir, Pibrentasvir |
| NS3/4A protease inhibitors | Viral polyprotein processing | Glecaprevir, Grazoprevir |
Preferred Regimens
Pangenotypic (covers all genotypes)
These are first-line choices in most current guidelines, eliminating the need for genotype testing before treatment:
| Regimen | Duration | Notes |
|---|---|---|
| Sofosbuvir/Velpatasvir (Epclusa) | 12 weeks | Preferred for genotypes 1–6; add ribavirin if decompensated cirrhosis |
| Glecaprevir/Pibrentasvir (Mavyret) | 8 weeks (treatment-naïve, no cirrhosis) | Can extend to 12–16 weeks for cirrhosis or treatment-experienced; approved in Australia 2018, NZ 2019 |
Genotype-Specific Regimens
| Regimen | Genotype | Duration | SVR |
|---|---|---|---|
| Sofosbuvir + Ledipasvir (Harvoni) | 1, 4, 5, 6 | 8–12 weeks (non-cirrhotic naïve); 24 weeks if cirrhotic/experienced | 94–99% |
| Elbasvir/Grazoprevir (Zepatier) | 1, 4 | 12 weeks | ~95% |
Per Harrison's (p. 9520): In treatment-naïve, non-cirrhotic genotype 1 patients with baseline HCV RNA <6 × 10⁶ IU/mL, 8 weeks of sofosbuvir/ledipasvir is as effective as 12 weeks (SVR 94–95%).
Special Populations
| Population | Considerations |
|---|---|
| Cirrhosis (compensated) | Standard regimens; monitor closely; may extend duration |
| Cirrhosis (decompensated) | Pangenotypic SOF/VEL + ribavirin; avoid NS3/4A protease inhibitors |
| Treatment-experienced | Most DAA regimens still effective; may extend to 12–16 weeks |
| Renal impairment / ESRD | Glecaprevir/Pibrentasvir preferred (no renal dose adjustment needed) |
| HIV co-infection | Check drug-drug interactions (DDIs); most DAA regimens effective |
| Children | DAA therapy approved for pediatric use |
| Substance use / mental health | These do NOT disqualify patients from DAA therapy; neuropsychiatric symptoms often improve during treatment (Treating Hepatitis C, p. 3) |
Monitoring
| Timepoint | Test |
|---|---|
| Baseline | HCV RNA (quantitative), genotype, LFTs, CBC, eGFR, HIV, HBsAg, pregnancy test |
| On-treatment (week 4) | HCV RNA (optional; assess adherence) |
| End of treatment | HCV RNA |
| SVR12 (12 wks post-treatment) | HCV RNA — primary cure endpoint |
| Post-SVR (cirrhotic patients) | HCC surveillance (ultrasound ± AFP every 6 months), ongoing liver assessment |
Drug Interactions
DAAs have important DDIs to check before prescribing:
- Antacids / PPIs: reduce sofosbuvir/ledipasvir absorption (separate timing)
- Rifampicin, St. John's Wort: potent inducers, contraindicated
- Statins: many require dose adjustments or are contraindicated with protease inhibitors
- Anticonvulsants (carbamazepine, phenytoin): reduce DAA levels
- Always use a DDI checker (e.g., HEP Drug Interactions)
HBV Reactivation Warning
Patients with active or prior HBV infection should be screened before starting DAAs. HBV reactivation can occur during or after HCV treatment — monitor and treat accordingly.
Key Takeaway
With current pangenotypic DAA regimens, the vast majority of HCV-infected patients — including those with cirrhosis, substance use, or psychiatric comorbidities — can be cured in 8–12 weeks with a once-daily oral pill and minimal side effects. This represents one of the most significant advances in modern medicine.
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