Red Flags
- Decompensated cirrhosis (Child-Pugh B/C) with HCV — avoid protease inhibitor-containing regimens (glecaprevir/pibrentasvir, voxilaprevir); use sofosbuvir/velpatasvir 12 weeks plus ribavirin[1]
- Acute hepatitis C — observe 12 weeks for spontaneous clearance OR treat per chronic protocol if persistent viraemia[1]
- HCV with HBV co-infection — risk of HBV reactivation during DAA therapy; check HBsAg and prophylactic antiviral if positive[1]
- HCV with significant DAA-affecting comedications (rifampicin, anticonvulsants, statins, amiodarone) — review interactions before treatment initiation[1]
First-line treatment
Interventions
- Test of cure 12 weeks post-treatment[1]HCV RNA at 12 weeks after end of treatment defines sustained virologic response (SVR12) — equivalent to cure
- HCC surveillance for cirrhotic patients post-cure[1]All cirrhotics continue 6-monthly ultrasound + AFP indefinitely; SVR does NOT eliminate HCC risk in cirrhotics
- Reinfection prevention in PWID[1]Counsel on harm reduction, opioid agonist therapy, sterile injection equipment; reinfection rate 4–8%/year in active PWID; treat reinfections
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Sofosbuvir/velpatasvir[1] | Pan-genotypic DAA combination (NS5B + NS5A inhibitors) | 400/100 mg PO once daily for 12 weeks (treatment-naive without cirrhosis); 12 weeks (compensated cirrhosis); 12 weeks + ribavirin (decompensated cirrhosis) | Per weight band ≥6 years | First-line pan-genotypic regimen; SVR ≥95% |
| Glecaprevir/pibrentasvir[1] | Pan-genotypic DAA combination (NS3/4A + NS5A inhibitors) | 300/120 mg PO once daily for 8 weeks (treatment-naive without cirrhosis or with compensated cirrhosis); 12 weeks for advanced fibrosis or specific genotypes | Per weight ≥3 years | Shortest pan-genotypic regimen; AVOID in decompensated cirrhosis (Child-Pugh B/C) |
| Sofosbuvir/velpatasvir/voxilaprevir (salvage)[1] | Pan-genotypic salvage DAA | 400/100/100 mg PO once daily for 12 weeks | — | Salvage regimen for DAA failure; AVOID in decompensated cirrhosis |
| Ribavirin (selected use)[1] | Nucleoside analogue | Weight-based: <75 kg = 1000 mg/day; ≥75 kg = 1200 mg/day; divided BD | 15 mg/kg/day divided BD | Add to sof/velpatasvir in decompensated cirrhosis or selected re-treatment; teratogenic — strict contraception both sexes |
Sofosbuvir/velpatasvir[1]
Pan-genotypic DAA combination (NS5B + NS5A inhibitors)
- Adult
- 400/100 mg PO once daily for 12 weeks (treatment-naive without cirrhosis); 12 weeks (compensated cirrhosis); 12 weeks + ribavirin (decompensated cirrhosis)
- Paediatric
- Per weight band ≥6 years
First-line pan-genotypic regimen; SVR ≥95%
Glecaprevir/pibrentasvir[1]
Pan-genotypic DAA combination (NS3/4A + NS5A inhibitors)
- Adult
- 300/120 mg PO once daily for 8 weeks (treatment-naive without cirrhosis or with compensated cirrhosis); 12 weeks for advanced fibrosis or specific genotypes
- Paediatric
- Per weight ≥3 years
Shortest pan-genotypic regimen; AVOID in decompensated cirrhosis (Child-Pugh B/C)
Sofosbuvir/velpatasvir/voxilaprevir (salvage)[1]
Pan-genotypic salvage DAA
- Adult
- 400/100/100 mg PO once daily for 12 weeks
- Paediatric
- —
Salvage regimen for DAA failure; AVOID in decompensated cirrhosis
Ribavirin (selected use)[1]
Nucleoside analogue
- Adult
- Weight-based: <75 kg = 1000 mg/day; ≥75 kg = 1200 mg/day; divided BD
- Paediatric
- 15 mg/kg/day divided BD
Add to sof/velpatasvir in decompensated cirrhosis or selected re-treatment; teratogenic — strict contraception both sexes
Safety-net
- Take DAA tablets daily without missing doses for the full 8–12 weeks; skipping doses risks resistance and treatment failure[1]
- Report any new medications to your hepatologist — DAAs interact with many drugs (rifampicin, anticonvulsants, statins, amiodarone)[1]
- Cured infection means undetectable HCV but you can still be re-infected if exposed; safe-injection and safe-sex advice still applies[1]
Referral criteria
- Decompensated cirrhosis with HCVHepatology specialist for DAA selection and transplant assessment[1]
- DAA failure on first-line treatmentHepatology for salvage regimen with resistance testing[1]
- HCV in pregnancyHepatology + maternal-fetal medicine; defer DAA until postpartum (no current DAA approved in pregnancy)[1]
- HCV in HIV / HBV / immunocompromisedHepatology + ID for combined management[1]
Clinical summary
Diagnosis and DAA-based eradication of chronic HCV; pan-genotypic combinations achieve >95% sustained virologic response.