Hepatitis C — chronic infection

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.

References

1.EASL Recommendations on Treatment of Hepatitis C: Final Update (2020); AASLD/IDSA HCV Guidance (continuously updated) (2020)

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