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  Conference on Retroviruses
and Opportunistic Infections
Seattle, Washington
March 4-7, 2019
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DAA therapy for HCV lowers risk of cardiovascular
disease at all fibrosis stages
  Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2019, Seattle
Mark Mascolini
Study of 65,000 US veterans linked direct-acting antiviral (DAA) therapy of HCV infection to lower risk of new cardiovascular disease at all fibrosis stages [1]. Veterans with the most advanced fibrosis enjoyed the greatest cardiovascular benefit with DAA therapy in this analysis of people with HCV but not HIV.
Research links HCV infection to higher cardiovascular disease rates. But the impact of HCV and HCV therapy on cardiovascular risk is complicated. Ongoing HCV infection lowers dangerous LDL cholesterol, which rebounds with successful DAA therapy. A 237-person Spanish study found that curing HCV in people with HIV boosted 10-year cardiovascular risk [2]. But an 18,736-person European analysis of people with HIV infection (reviewed separately by NATAP) did not tie successful HCV therapy to incident (newly diagnosed) cardiovascular disease [3].
US Veterans Affairs (VA) researchers mounted this study to explore the impact of baseline liver fibrosis stage on risk of new cardiovascular disease in DAA-treated people with HCV but without HIV [1]. They also wanted to compare cardiovascular disease incidence in that group with incidence in veterans not treated for HCV or treated with older pegylated interferon regimens.
The study used data from ERCHIVES, an established US national cohort of HCV-infected veterans. The VA researchers identified everyone treated with DAAs for more than 7 weeks and matched them by propensity score to untreated or interferon-treated veterans. They excluded veterans with HIV, HBV, or previously diagnosed cardiovascular disease. Determining fibrosis stage by FIB-4 score, the researchers stratified cardiovascular disease incidence and risk factors by fibrosis stage. They identified new cardiovascular disease by ICD-9/10 codes and used Kaplan-Meier analysis to compare cardiovascular disease-free survival by fibrosis stage and HCV treatment.
The analysis involved 32,575 DAA-treated veterans and the same number of matched untreated veterans. Median ages of the treated and untreated groups were 58.6 and 57.5 years, about 56% of both groups were white, about 27% were black, and 96% were men. Similar proportions of the treated and untreated groups had a FIB-4 score below 1.25 (about 21%), 1.26 to 3.25 (about 52%), and above 3.25 (about 26%). In the treated group, 75% attained sustained virologic response (cure).
Cardiovascular disease incidence per 1000 person-years of follow-up was lower in the treated group across the 3 FIB-4 stages, and the difference was greatest in those with the worst fibrosis:
-- FIB-4 > 3.25: 24.5 treated vs 44 untreated (difference 19.5)
-- FIB-4 1.26 to 3.25: 19.9 treated vs 33.2 untreated (difference 13.3)
-- FIB-4 < 1.25: 19.3 treated vs 25.6 untreated (difference 6.3)
The VA team concluded that cardiovascular disease risk in people with HCV is higher at higher liver fibrosis stages. DAA therapy reduced that risk at all fibrosis stages, with the greatest impact in people with the worst fibrosis. The researchers proposed that "HCV-infected persons with more advanced liver fibrosis should be targeted for treatment to reduce risk of cardiovascular disease events."
1. Butt AA, Yan P, Aslam S, et al. Effect of liver fibrosis stage and DAA treatment on risk of CVD events in ERCHIVES. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 570.
2. Carrero A, Berenguer J, Hontanon V, Navarro J. Eradication of HCV: effects on cardiovascular risk and preclinical atherosclerosis. Conference on Retroviruses and Opportunistic Infections (CROI). March 2018. Boston. Abstract 631. http://www.croiconference.org/sessions/eradication-hcv-effects-cardiovascular-risk-and-preclinical-atherosclerosis
3. Peters L, Lundgren J, Rockstroh J, et al. Clinical outcomes in persons coinfected with HIV and HCV: impact of HCV treatment. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 565.