Decision support only — confirm the live PBS restriction and interaction checker before prescribing. Decompensated cirrhosis, prior DAA failure, pregnancy and transplant patients need specialist input.
1 The treatment decision in four steps
Confirm current infectionantibody is exposure, RNA is viraemia
Screen with anti-HCV; request reflex HCV RNA. A positive antibody persists after cure and does not diagnose active infection.
Detectable HCV RNA → stage and treat. Undetectable RNA → resolved infection or intermittent early viraemia; use exposure timing and repeat RNA. Australian HCV
Stage before selectingcirrhosis changes treatment and follow-up
History/exam; FBC, LFT/albumin, INR, eGFR; FIB-4/APRI ± transient elastography. Screen HBV/HIV, pregnancy and drug interactions.
Separate no cirrhosis, compensated and decompensated disease. Genotype is optional for first-line pangenotypic therapy, but record prior treatment.
Treat most peopleSVR exceeds 95% with first-line DAA
Chronic HCV; or early infection when transmission risk favours treatment. Active drug use, stable mental illness and homelessness are not exclusions.
Choose SOF/VEL or GLE/PIB for treatment-naïve, non-decompensated infection; use the shorter safe regimen the patient can finish. PBS
Specialist pathwaydo not improvise
Child–Pugh B/C, prior NS5A failure, transplant, complex DDI, HBV coinfection, pregnancy, suspected HCC or uncertain cirrhosis.
Discuss before the first tablet. Protease-inhibitor regimens are unsafe in decompensated liver disease.
PBS evidence of chronic infection currently requires anti-HCV positivity and repeated RNA positivity. The Australian acute-HCV pathway and AASLD/IDSA “test-and-treat” approach are therefore not perfectly aligned.
2 Pretreatment checklist
Virus and liver
- ConfirmHCV RNA; estimated duration; previous negative test/seroconversion if acute infection is plausible.
- StageFIB-4/APRI ± elastography. Cirrhosis: ultrasound for HCC within 3 months, assess CSPH and bone health. Australian HCV
- BaselineFBC, ALT/AST/ALP/GGT/bilirubin/albumin, INR, eGFR; HCV RNA quantity may help.
Coinfection and host
- HBVHBsAg, anti-HBc and anti-HBs. If HBsAg positive: HBV DNA and specialist plan for reactivation risk.
- HIVTest all; same DAA efficacy, but reconcile ART interactions.
- PreventHAV/HBV vaccination if susceptible; assess pregnancy, alcohol, metabolic cofactors and reinfection risk.
Medication reconciliation
- All drugsPrescription, OTC, supplements and recreational substances. Use a current HCV interaction checker.
- Red flagsAmiodarone with sofosbuvir; acid suppression with velpatasvir; statins, anticonvulsants, rifamycins and ART; ethinyloestradiol with GLE/PIB.
- Do not waitIf fibrosis/HBV/HIV testing will cause loss to follow-up, start a safe pathway and complete tests within the guideline window.
3 PBS-listed pangenotypic regimens
| Setting | Regimen | Practical points |
|---|
| Treatment-naïve; no cirrhosis | sofosbuvir/velpatasvir 400/100 mg once daily × 12 weeks OR glecaprevir/pibrentasvir 300/120 mg once daily × 8 weeks | GLE/PIB is three tablets together with food. SOF/VEL is one tablet; manage acid suppression. PBS/Australian HCV |
| Treatment-naïve; compensated cirrhosis | SOF/VEL × 12 weeks OR GLE/PIB × 8 weeks; a 12-week GLE/PIB course may be chosen in selected cirrhosis pathways. | Confirm Child–Pugh A and no prior decompensation. Continue cirrhosis surveillance after cure. |
| Prior NS5A-containing DAA failure | sofosbuvir/velpatasvir/voxilaprevir 400/100/100 mg once daily with food × 12 weeks | Specialist-led; verify resistance/history and PBS authority. Not for decompensated disease. |
| Decompensated Child–Pugh B/C | SOF/VEL + ribavirin × 12 weeks; ribavirin commonly starts 600 mg/day then is adjusted. If ribavirin-ineligible: SOF/VEL × 24 weeks. | No GLE/PIB and no SOF/VEL/VOX. Refer to hepatology/transplant; anaemia, renal function and pregnancy risk govern ribavirin. Australian HCV |
4 Acute infection and exposure
Australia: treat transmission risk, otherwise observe safely
- DiagnoseBest evidence is documented seroconversion or new RNA after a prior negative test. No single test cleanly separates acute from chronic infection.
- Treat earlyRecommended when ongoing transmission risk is present; use a standard chronic-infection DAA regimen. PBS chronicity restriction may affect access.
- ObserveIf deferring: HCV RNA, ALT/AST, bilirubin and INR every 2–6 weeks for 6 months. Confirm spontaneous clearance with two undetectable RNA tests ≥1 month apart.
Where international advice differs
- AASLD/IDSARecommends treatment as soon as quantifiable acute viraemia is diagnosed, without waiting for spontaneous resolution. Class I, B
- PEPNo DAA post-exposure prophylaxis. Obtain baseline serology/RNA and follow the occupational-exposure pathway.
- EscalateINR >1.5 or encephalopathy → immediate transplant-centre discussion; acute HCV liver failure is rare but dangerous.
5 During treatment
Keep it finishable
- ReviewContact early enough to find missed doses, new medicines, adverse effects or unstable housing. Routine on-treatment RNA is usually unnecessary.
- HBVAny ALT flare during/after DAA treatment should trigger HBV-reactivation review; HBsAg-positive patients need a pre-agreed monitoring or antiviral plan.
- RenalRecheck if clinically unstable, using ribavirin or advanced CKD; regimen selection and co-medications matter more than HCV genotype.
Pregnancy and ribavirin
- DAADo not routinely treat during pregnancy or breastfeeding; discuss specialist exceptions/research pathways.
- RibavirinTeratogenic. Avoid pregnancy in patients and partners during therapy and for 6 months after the last dose.
- ContraceptionGLE/PIB is contraindicated with ethinyloestradiol-containing contraception; reconcile before prescribing.
6 Prove cure, then decide who stays in care
| Result / risk | Action | Do not forget |
|---|
| End of treatment | Do not call cure from an end-of-treatment RNA. Arrange HCV RNA 12 weeks after completion; SVR4 may be used opportunistically when loss to follow-up is likely. | Amend the record to show cured HCV once SVR is confirmed. |
| SVR, no cirrhosis, normal LFT | No liver-specific HCV follow-up; manage as a person without active HCV. | Annual HCV RNA, not antibody, if reinfection risk continues. |
| SVR with cirrhosis | Continue HCC surveillance indefinitely and CSPH/variceal pathway. Selected patients with LSM <12 kPa, platelets ≥150 ×10⁹/L, normal LFT and no cofactors can leave CSPH surveillance. | That exception does not stop HCC surveillance. Australian HCV |
| RNA detected after treatment | Check timing, adherence, interactions and exposure; distinguish relapse from reinfection using history ± genotype/sequence. | Refer for salvage planning; resistance testing is selective, not automatic. |
7 Refer early when the liver is already failing
- Transplant assessmentChild–Pugh ≥B7, MELD ≥13, refractory ascites, SBP, HRS, recurrent/chronic encephalopathy, small HCC or severe malnutrition. Australian HCV
- MELD >15If a transplant candidate, the transplant physician should decide whether DAA treatment is better before or after transplantation; cure can improve liver function but may alter organ-access strategy.
- Other urgentNew decompensation, rapid synthetic decline, suspicious HCC, uncontrolled coinfection or severe treatment toxicity.
Guidelines & reviews. Australian recommendations for management of HCV infection, living website and 2022 consensus; Australian PBS General Statement for hepatitis C and current medicine listings; AASLD/IDSA HCV Guidance, acute infection; Liverpool HEP interaction resource. Trials. ASTRAL-1/2/3/4 (sofosbuvir/velpatasvir); EXPEDITION-8 (8-week glecaprevir/pibrentasvir in compensated cirrhosis); POLARIS-1/4 (sofosbuvir/velpatasvir/voxilaprevir salvage). Caveats. PBS authority wording and interaction data change. Verify live criteria, product information and local specialist access. Australian acute-HCV recommendations retain an observation option when transmission risk is low; AASLD/IDSA recommends immediate treatment.