Direct-Acting Antivirals and Risk of Hepatitis C Extrahepatic Manifestations
Authors' conclusion
In this cohort study of 22 576 individuals with chronic HCV infection, successful HCV treatment with DAAs was associated with lower risk of several EHMs. These findings highlight the importance of early HCV screening and treatment to prevent EHMs and improve overall health outcomes.
Study context
- Population
- Individuals with chronic Hepatitis C virus (HCV) infection, BC Hepatitis Testers Cohort, British Columbia, Canada; mean age at HCV diagnosis 42.0 years, 66.2% male
- Participants
- 22,576 individuals
- Exposure
- Successful direct-acting antiviral (DAA) treatment vs no treatment
- Treated with sustained virologic response (SVR)n = 11,953
- Treated without SVRn = 386
- Untreatedn = 10,237reference
- Outcome
- Incidence of 5 groups of extrahepatic manifestations: CKD and ESKD, T2D, stroke, MACE, neurocognitive disorders
- Follow-up
- Median 2.5 years
Methodological detailsmatched by year of HCV diagnosis, inverse probability of treatment weighting (inverse probability of treatment weights (IPTW)), Data from 1990 to 2021; analyzed February 2024 to March 2025
- Matched by year of HCV diagnosis
- Inverse probability of treatment weighting (IPTW)
- Data from 1990 to 2021; analyzed February 2024 to March 2025
Main finding
As reported in the abstract
Incidence of 5 EHM groups: CKD and ESKD, T2D, stroke, MACE, NCD
Untreated
- CKD and ESKD
- 21.0 (95% CI, 19.0-23.1)
- Stroke
- 8.9 (95% CI, 7.7-10.2)
- Major adverse cardiac events (MACE)
- 26.7 (95% CI, 24.5- 29.1)
- Neurocognitive disorders (NCD)
- 19.2 (95% CI, 17.3-21.2)
- T2D
- 6.4 (95% CI, 5.4-7.7)
Treated with SVR
- CKD and ESKD
- 14.7 (95% CI, 13.4-16.1)
- Stroke
- 6.3 (95% CI, 5.5-7.2)
- MACE
- 19.3 (95% CI, 17.8-20.9)
- NCD
- 10.3 (95% CI, 9.2-11.5)
- T2D
- 9.2 (95% CI, 8.1-10.4)
CKD and ESKD
Untreated21.0 (95% CI, 19.0-23.1)
Treated with SVR14.7 (95% CI, 13.4-16.1)
Stroke
Untreated8.9 (95% CI, 7.7-10.2)
Treated with SVR6.3 (95% CI, 5.5-7.2)
Major adverse cardiac events (MACE)
Untreated26.7 (95% CI, 24.5- 29.1)
Treated with SVR19.3 (95% CI, 17.8-20.9)
Neurocognitive disorders (NCD)
Untreated19.2 (95% CI, 17.3-21.2)
Treated with SVR10.3 (95% CI, 9.2-11.5)
T2D
Untreated6.4 (95% CI, 5.4-7.7)
Treated with SVR9.2 (95% CI, 8.1-10.4)
acsHR
- CKD and ESKD
- 0.54 (95% CI 0.47–0.63)
- Stroke
- 0.66 (95% CI 0.54–0.81)
- MACE
- 0.58 (95% CI 0.52–0.66)
- NCD
- 0.52 (95% CI 0.45–0.61)
Observational data: associations, not effects.
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
Direct-Acting Antivirals and Risk of Hepatitis C Extrahepatic Manifestations. JAMA Netw Open. Published 2 June 2025. doi:10.
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