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. The main exception is non-HCV illness limiting life expectancy to <12 months.
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.
Who to test: test anyone with a current or past HCV risk factor: injecting drug use, custody, tattoos/body piercing, transfusion or transplant in Australia before 1990, clotting-factor concentrate before 1993, maternal exposure, HBV/HIV, persistently raised ALT, needlestick exposure, relevant sexual risk or migration from a high-prevalence region. Repeat at least annually while exposure risk continues; after previous infection or cure, use HCV RNA, not antibody. Point-of-care HCV RNA can shorten diagnosis-to-treatment in high-prevalence services; use a validated, pathology-linked quality-assurance pathway. Australian HCV
2 Pretreatment checklist
Virus and liver
- ConfirmHCV RNA; estimated duration; previous negative test/seroconversion if acute infection is plausible.
- StageFIB-4/APRI ± elastography. FIB-4 <1.45 or APRI <1.0 helps exclude cirrhosis; higher values do not diagnose it. 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 prompt fibrosis or HBV/HIV testing is impractical and loss to follow-up is likely, do not defer a safe DAA pathway. Stage in parallel; complete HBV/HIV testing within 4 weeks of starting. Australian HCV
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 |
| Renal impairment, including dialysis | No DAA dose adjustment for SOF/VEL, GLE/PIB or SOF/VEL/VOX. | eGFR <30 mL/min/1.73 m² or dialysis → specialist/renal input. Ribavirin accumulates and requires specialist dosing plus haemoglobin monitoring. 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 unnecessary; detectable week-4 RNA occurs in up to 20% and does not predict failure or justify extension.
- HBVHBsAg positive → baseline HBV DNA. Start tenofovir/entecavir before DAA if cirrhosis or HBV DNA >2,000 IU/mL; if untreated below that threshold, monitor ALT every 4 weeks and HBV DNA every 12 weeks through SVR. Any ALT flare needs reactivation review. Australian HCV
- Interruption<7 days: resume and finish. >7 days in the first 4 weeks: restart a full course. >7 days after week 4: obtain HCV RNA; if positive, manage as treatment failure with specialist salvage. Australian HCV
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 liver ultrasound ± AFP every 6 months, indefinitely, plus the 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. |
Cure does not confer immunity, and there is no HCV vaccine. Offer retreatment after reinfection. Pair testing and treatment with sterile injecting equipment/needle-and-syringe programs, opioid agonist treatment where relevant, and safer injecting, tattooing and piercing advice. A positive antibody result should trigger reflex RNA and active linkage, not another appointment that may never happen. Offer peer support, interpreters and ACCHO or other culturally safe services when they improve access. Sixth National Strategy
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.
- Active/prior HCCDo not withhold cure because of the old recurrence concern: available data do not show that DAAs increase HCC recurrence. Individualise treatment timing with the HCC multidisciplinary team and keep surveillance running.
- Other urgentNew decompensation, rapid synthetic decline, suspicious HCC, uncontrolled coinfection or severe treatment toxicity.
Primary clinical source. Australian recommendations for the management of hepatitis C virus infection: a consensus statement (2022) and living website, including the National HCV Point-of-Care Testing Program; Australian PBS General Statement for hepatitis C and current medicine listings. Policy/context. Sixth National Hepatitis C Strategy 2025–2030, which supersedes the Fifth Strategy 2018–2022; AASLD/IDSA HCV Guidance, acute infection; Liverpool HEP interaction resource. Key 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.