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  Conference on Retroviruses
and Opportunistic Infections
Seattle, Washington
March 4-7, 2019
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HCV treatment with DAAs halves risk of new diabetes diagnosis
  Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2019, Seattle
Mark Mascolini
Treatment of HCV infection with direct-acting antivirals (DAAs) halved the risk of subsequent diabetes in a study of 52,000 US veterans with HCV but not HIV [1]. This lowered risk was most pronounced in people with more advanced liver disease.
Ample research confirms a higher risk of diabetes in people with HCV infection. Studies suggested a link between older interferon/ribavirin treatment for HCV and new-onset diabetes, while newer work indicates that DAAs promote blood sugar control. Researchers from the VA Pittsburgh Healthcare System and collaborators at other centers conducted this study to compare diabetes incidence in HCV patients taking a DAA regimen, those treated with pegylated interferon/ribavirin (PEG/RBV), and untreated people with HCV. The primary outcome was newly diagnosed (incident) diabetes more than 12 weeks after baseline.
The investigators scrutinized data from ERCHIVES, a regularly updated database of US veterans with HCV and uninfected controls. They identified all veterans with new chronic HCV infection (HCV antibody positive and at least one positive HCV RNA). They excluded veterans infected with HIV or HBV, those with prevalent diabetes, and those treated with both DAAs and PEG/RBV. For each treated veteran, the researchers selected a propensity score-matched untreated control with HCV. Treatment meant at least 8 weeks of therapy with any FDA-approved DAA regimen or at least 24 weeks of PEG/RBV.
The investigators used Cox proportional hazards models to determine factors associated with newly diagnosed diabetes; they used Kaplan-Meier analysis to compare diabetes-free survival by treatment status, attainment of sustained virologic response (SVR), body mass index, and liver disease severity.
The analysis included 26,043 veterans treated for HCV and the same number of untreated controls. The treated group was significantly older than the untreated group (median 61 versus 58, P < 0.0001), included a slightly higher proportion of whites and lower proportions of blacks and Hispanics (P < 0.0001), and had a higher proportion with more advanced liver disease (FIB-4 score > 3.25, 22.3% versus 16.25%, P < 0.001). Most participants in both groups, 96%, were men.
Diabetes incidence proved significantly lower in treated than untreated veterans (15.4 versus 20.6 per 1000 person-years, P < 0.0001). DAA therapy drove this difference (DAA incidence 9.89 per 1000, P < 0.0001; PEG/RBV incidence 19.8 per 1000, P = 0.39; untreated incidence 20.6 per 1000). Diabetes incidence was also significantly lower in veterans who attained SVR than in those who did not (13.3 versus 19.2 per 1000, P < 0.0001). The incidence difference between untreated and treated participants was more marked in groups with worse liver disease (higher FIB-4).
Cox modeling identified several factors independently associated with incident diabetes, at the following hazard ratios (HR) and 95% confidence intervals (CI):
-- Black vs white race: HR 1.42, 95% CI 1.29 to 1.56, P < 0.0001
-- Hispanic vs white race: HR 1.29, 95% CI 1.08 to 1.54, P = 0.01
-- Male vs female: HR 1.83, 95% CI 1.43 to 2.34, P < 0.0001
-- Body mass index 25 to 29.99 vs <18.5: HR 1.88, 95% CI 1.23 to 2.87, P = 0.004
-- Body mass index >30 vs <18.5: HR 3.38, 95% CI 2.21 to 5.17, P < 0.0001
-- FIB-4 >3.25 vs <1.25: HR 1.29, 95% CI 1.13 to 1.46, P = 0.0001
-- Every 10-fold higher HCV RNA: HR 0.98, 95% CI 0.96 to 0.99, P = 0.003
-- Any DAA vs no treatment: HR 0.48, 95% CI 0.42 to 0.56, P < 0.0001
Notably, DAA therapy halved the risk of incident diabetes, but PEG/RBV had no significant impact on diabetes risk (HR 0.96, 95% CI 0.86 to 1.06 P = 0.38).
The ERCHIVES team proposed that "treatment of HCV with DAA regimens confers benefits beyond virologic control and may be useful in controlling or mitigating some of the extrahepatic complications of HCV."
1. Butt AA, Aslam S, Yan P, Shaikh OS, Abou-Samra AB. Incident diabetes and glucose control after HCV treatment with DAAs in ERCHIVES. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 88.