Background and importance
Hepatitis C virus (HCV) infection extends far beyond liver-related complications, triggering chronic systemic inflammation that leads to extrahepatic manifestations including type 2 diabetes, cardiovascular and cerebrovascular diseases, neurocognitive disorders, and kidney dysfunction. The majority of patients with chronic HCV infection develop one or more of these serious conditions, significantly impacting their long-term health outcomes.
The introduction of direct-acting antivirals (DAAs) revolutionized HCV treatment with highly effective oral medications that achieve cure rates of approximately 95% after just eight to 12 weeks of once-daily treatment. In Canada, DAAs became available in 2014 with initial access restrictions, but universal public access was achieved by 2018, creating an opportunity to assess the broader health benefits of HCV cure beyond liver-related outcomes.
Summary of evidence
Using the BC Hepatitis Testers Cohort, we examined whether successful DAA treatment reduces extrahepatic manifestation risks among people with chronic HCV infection in British Columbia. Among 22,576 individuals, we assessed the impact of treatment on chronic kidney disease, stroke, major adverse cardiac events, and neurocognitive disorders. Results showed that successful DAA treatment significantly reduced the risk of developing chronic kidney disease, end-stage renal disease, stroke, major adverse cardiac events, and neurocognitive disorders, but had no significant effect on diabetes risk.
Implications for practice
These findings demonstrate substantial health benefits of HCV treatment beyond liver outcomes, strengthening the case for comprehensive HCV screening and early treatment initiation. Healthcare systems should prioritize accessible HCV care to reduce disease transmission and improve overall population health. However, the lack of diabetes risk reduction warrants further investigation and continued diabetes monitoring in patients even after successful HCV treatment.
For further information
Jeong D, Wong S, Karim ME, et al. Direct-acting antivirals and risk of hepatitis C extrahepatic manifestations. JAMA Network Open. 2025 Jun 2;8(6):e2514631. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2835177
Acknowledgements
Authors would like to thank Sara Qureshi and Georgine Cua for the graphical abstract.
