📋 Key Information Summary
- Diagnosis requires anti-HCV antibody test followed by HCV RNA confirmation; RNA positivity defines active infection.
- All patients with chronic HCV require assessment of liver fibrosis using non-invasive tests (FibroScan, APRI, FIB-4) to guide treatment urgency and follow-up.
- Pan-genotypic direct-acting antiviral (DAA) regimens are first-line; routine genotype testing is no longer mandatory for treatment selection.
- Standard first-line regimens: Sofosbuvir/velpatasvir for 12 weeks, or glecaprevir/pibrentasvir for 8 weeks (treatment-naïve, non-cirrhotic).
- For compensated cirrhosis (Child-Pugh A), extend glecaprevir/pibrentasvir to 12 weeks; decompensated cirrhosis (Child-Pugh B/C) contraindicates protease inhibitors.
- DAA retreatment for prior failure: sofosbuvir/velpatasvir/voxilaprevir for 12 weeks is highly effective.
- HIV co-infection is not a barrier to treatment; check for drug interactions with antiretrovirals.
- Screen for and manage HBV co-infection due to risk of reactivation during DAA therapy; consider prophylactic antivirals.
- All DAAs, including those with protease inhibitors, are safe in severe renal impairment (eGFR <30 mL/min); no dose adjustment required.
- People who inject drugs should be actively offered treatment; ongoing drug use is not a contraindication.
- Achievement of SVR (sustained virological response) does not eliminate risk of hepatocellular carcinoma in those with pre-existing cirrhosis; lifelong surveillance is required.
- Post-SVR, monitor for reinfection in at-risk individuals with annual HCV RNA testing.
- Address comorbidities including alcohol use and metabolic dysfunction-associated steatotic liver disease (MASLD).
- Aboriginal and Torres Strait Islander peoples experience higher prevalence and require culturally safe, community-based approaches to testing and treatment.
Diagnosis & Assessment
Diagnostic Pathway
The diagnosis of hepatitis C virus (HCV) infection follows a two-step serological and virological pathway. Initial screening is with an anti-HCV antibody test. A positive result must be confirmed by a qualitative or quantitative HCV RNA test to distinguish resolved past infection from current active infection.
Critical Note: A positive anti-HCV antibody test with a negative HCV RNA result indicates past, resolved infection. These patients do not require antiviral therapy but may have residual liver damage requiring assessment.
Baseline Investigations
A comprehensive baseline assessment is essential for treatment planning and safety monitoring.
Essential
HCV RNA (viral load)
Quantitative PCR to confirm active infection and provide a baseline for monitoring treatment response. MBS item 69496.
Available
HCV Genotype
Now less critical with pan-genotypic DAAs, but may guide therapy in complex cases (e.g., prior DAA failure, cirrhosis). MBS item 69499.
Essential
Liver Fibrosis Assessment
Non-invasive tests are first-line: FibroScan (transient elastography) or serological markers (APRI, FIB-4). Liver biopsy reserved for uncertain non-invasive results or alternative diagnoses.
Essential
Co-infection Screening
HIV antibody/antigen, Hepatitis B surface antigen (HBsAg), anti-HBc, anti-HBs. Critical for managing reactivation risks and drug interactions.
Essential
Full Blood Count, LFTs, Renal Function (eGFR)
Assess for cytopenias, synthetic function (albumin, INR), and renal impairment to guide DAA safety.
Fibrosis Staging
Accurate staging of liver fibrosis is crucial as it determines treatment urgency, regimen choice, and post-treatment surveillance.
| Method | Description & Scoring | Interpretation |
|---|---|---|
| FibroScan (Transient Elastography) | Measures liver stiffness in kPa. Non-invasive, operator-dependent. | F0-2: <9.5 kPa; F3 (advanced fibrosis): 9.5-12.5 kPa; F4 (cirrhosis): >12.5 kPa. |
| APRI Score | (AST/ULN) / Platelet count (x10⁹/L) x 100. Simple laboratory-based score. | <0.5 rules out significant fibrosis; >1.5 suggests cirrhosis. |
| FIB-4 Index | (Age x AST) / (Platelet count x √ALT). Incorporates age. | <1.45 rules out advanced fibrosis; >3.25 suggests advanced fibrosis/cirrhosis. |
| Liver Biopsy | Histological assessment (METAVIR score). Gold standard but invasive. | F0: No fibrosis; F1: Portal; F2: Few septa; F3: Many septa; F4: Cirrhosis. |
DAA Therapy
Direct-acting antivirals (DAAs) are the cornerstone of HCV treatment, offering cure rates >95%. Pan-genotypic regimens have simplified treatment. Choice of regimen depends on fibrosis stage, prior treatment history, and comorbidities.
First-Line Pan-Genotypic Regimens
Sofosbuvir / Velpatasvir
Epclusa® · NS5B + NS5A inhibitor
Adult dose
One tablet (400/100 mg) PO once daily
Duration (naïve, non-cirrhotic)
12 weeks
Duration (compensated cirrhosis)
12 weeks
Renal impairment
Safe in all stages, including dialysis. No dose adjustment.
PBS status
✔ PBS General Benefit
Glecaprevir / Pibrentasvir
Mavyret® · NS3/4A + NS5A inhibitor
Adult dose
Three tablets (300/120 mg) PO once daily with food
Duration (naïve, non-cirrhotic)
8 weeks
Duration (compensated cirrhosis, Child-Pugh A)
12 weeks
Key consideration
Contains a protease inhibitor (glecaprevir). Contraindicated in decompensated cirrhosis (Child-Pugh B/C).
PBS status
✔ PBS General Benefit
Special Circumstances & Retreatment
Decompensated Cirrhosis (Child-Pugh B/C): Protease inhibitors (glecaprevir, voxilaprevir) are contraindicated due to risk of further decompensation. Use sofosbuvir/velpatasvir ± ribavirin for 12-24 weeks under specialist supervision.
Sofosbuvir / Velpatasvir / Voxilaprevir
Vosevi® · NS5B + NS5A + NS3/4A inhibitor
Indication
Retreatment for prior DAA failure, particularly NS5A inhibitor failures.
Adult dose
One tablet (400/100/100 mg) PO once daily with food
Duration
12 weeks
Contraindication
Decompensated cirrhosis (Child-Pugh B/C). Avoid with strong OATP1B inhibitors.
PBS status
⚠️ PBS Authority Required
Special Populations
DAA therapy is highly effective across diverse patient groups. Treatment should not be delayed or denied based on the factors below.
HIV Co-infection
Key Principle: All HIV/HCV co-infected patients should receive DAA therapy. HCV treatment does not interfere with HIV control.
Drug Interactions: Critical to review with antiretroviral therapy (ART). Key interactions include:
- Glecaprevir/Pibrentasvir: Avoid with atazanavir, darunavir. Safe with dolutegravir, bictegravir.
- Sofosbuvir/Velpatasvir: Fewer interactions; generally safe with most INSTIs.
- Tip: Consult the Liverpool HIV Drug Interactions Database.
HBV Co-infection
Risk: HBV reactivation can occur during/after DAA therapy, leading to hepatic failure. Risk is highest in HBsAg-positive patients.
Management:
- HBsAg Positive: Start prophylactic entecavir or tenofovir (alongside DAAs) and continue for 12-24 weeks post-DAA.
- HBsAg Negative, anti-HBc Positive: Monitor HBV DNA monthly during and for 6 months after DAA therapy. Treat if reactivation occurs.
Chronic Kidney Disease (CKD)
Safety: All current pan-genotypic DAA regimens (including those with protease inhibitors) are safe in severe CKD (eGFR <30 mL/min) and dialysis. No dose adjustments required.
Preferred Regimens: Glecaprevir/pibrentasvir (8-12 weeks) or sofosbuvir/velpatasvir (12 weeks) are standard. Ribavirin should be avoided if significant anaemia is present.
Post-Liver Transplant
Indication: Treat all patients with recurrent HCV post-transplant to prevent graft fibrosis and cirrhosis.
Timing & Regimen: Initiate once stable (usually 3-6 months post-transplant). Use sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for 12 weeks. Crucial: Manage drug interactions with immunosuppressants (e.g., calcineurin inhibitors).
People Who Inject Drugs (PWID)
Key Principle: Active injecting drug use is NOT a contraindication to treatment. Treatment as prevention is a public health goal.
Recommendations:
- Offer treatment in conjunction with harm reduction services (needle/syringe programmes, OST).
- Adherence and SVR rates in PWID are comparable to other populations with appropriate support.
- Address reinfection risk through education and ongoing engagement.
Post-SVR & Follow-up
Achievement of a Sustained Virological Response (SVR, defined as undetectable HCV RNA 12 weeks post-treatment) indicates cure. However, ongoing management is essential.
Key Follow-up Components
1
Hepatocellular Carcinoma (HCC) Surveillance
For patients with pre-treatment cirrhosis (F4) or advanced fibrosis (F3), the risk of HCC persists despite SVR. Lifelong six-monthly liver ultrasound ± alpha-fetoprotein (AFP) is mandatory. MBS item 11000 (ultrasound).
2
Reinfection Screening
For individuals with ongoing risk (e.g., PWID, men who have sex with men with risk behaviours), annual HCV RNA testing is recommended to detect reinfection early for re-treatment.
3
Monitor for Decompensation
In patients with pre-existing cirrhosis, monitor for signs of hepatic decompensation (ascites, encephalopathy, variceal bleeding) even after SVR. Refer for gastroenterology/hepatology follow-up.
4
Address Comorbidities
Counselling and management for alcohol use disorders. Screen and manage metabolic dysfunction-associated steatotic liver disease (MASLD) through weight management, diabetes, and lipid control.
Cure does not mean immunity. Reinfection is possible. Emphasise harm reduction strategies to patients with ongoing risk behaviours.
Aboriginal and Torres Strait Islander Health
Aboriginal and Torres Strait Islander Health Considerations
Hepatitis C disproportionately affects Aboriginal and Torres Strait Islander peoples, with higher prevalence, incidence, and morbidity. A culturally safe, holistic, and community-controlled health service-led approach is essential.
📚 References
- 1. World Health Organization. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. Geneva: WHO; 2024.
- 2. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C: Final update of the series. J Hepatol. 2023;79(4):1005-1036.
- 3. Australian Government Department of Health. National Hepatitis C Strategy 2023–2030. Canberra: Commonwealth of Australia; 2023.
- 4. The Kirby Institute. HIV, viral hepatitis and sexually transmissible infections in Australia: Annual surveillance report 2023. Sydney: UNSW; 2023.
- 5. Australian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM). Quick Reference Guide: Hepatitis C Management in the DAA Era. Sydney: ASHM; 2022.
- 6. Pharmaceutical Benefits Scheme (PBS). Sofosbuvir with velpatasvir (Epclusa). Australian Government Department of Health. Accessed 2024.
- 7. Pharmaceutical Benefits Scheme (PBS). Glecaprevir with pibrentasvir (Mavyret). Australian Government Department of Health. Accessed 2024.
- 8. Hepatitis B Virus Reactivation in Patients with Hepatitis C Virus Treated with Direct-Acting Antivirals: A Systematic Review and Meta-analysis. Clin Infect Dis. 2022;74(8):1435-1444.
- 9. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander health performance framework 2023 summary report. Canberra: AIHW; 2023.
- 10. National Aboriginal Community Controlled Health Organisation (NACCHO). Position Statement: Viral Hepatitis. Canberra: NACCHO; 2022.
- 11. Martinello M, et al. Simplified monitoring for hepatitis C virus treatment with sofosbuvir plus ribavirin in the REASON study. J Viral Hepat. 2023;30(2):156-167.
- 12. Dore GJ, et al. Glecaprevir/Pibrentasvir for 8 Weeks in Treatment-Naïve Patients with HCV Genotypes 1-6 and Compensated Cirrhosis: The EXPEDITION-8 Trial. Hepatology. 2022;75(3):670-681.