Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes

Abstract

Background:The role of hepatitis C (HCV) eradication on the long-term complications of type 2 diabetes mellitus remains incompletely studied.Aim: To investigate whether antiviral treatment impacted risk of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS). Methods:We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine-Gray subdistribution hazard ratio [sHR]), with death as a competing event.Results: Among 1395 HCV-infected patients with type 2 diabetes, 723 (52%) were treated with either interferon-based or direct-acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end-stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA-treated patients and interferon-treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause-specific hazards, exclusion of patients with on-treatment retinopathy, and treatment status as a time-varying covariate.Conclusion: Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection

“…HCV anti‐viral therapy with attainment of sustained virological response (SVR), which is virological cure, has hepatic benefits, such as normalising liver enzymes, halting the progression of liver disease and reducing the risk of hepatocellular carcinoma. Studies in the interferon‐based treatment era showed that SVR was also associated with a reduced risk of mixed cryoglobulinaemia; glomerulonephritis; porphyria cutanea tarda; NHL; and, possibly, diabetes mellitus …”

A review of the use of time‐varying covariates in the Fine‐Gray subdistribution hazard competing risk regression model

“…Of the 55 papers published in 2015, six (11%) included time‐varying covariates in Fine‐Gray subdistribution hazard model . Of the 102 papers published in the first 5 months of 2019, five (5%) included time‐varying covariates in the Fine‐Gray subdistribution hazard model . These 11 papers are summarized in Table .…”

“…Of the 11 studies that incorporated time‐varying covariates, six (55%) provided, in at least one instance, an interpretation that suggested that the time‐varying covariate was associated with the risk of the event . As risk has a distinct probabilistic interpretation, it appears that these authors were suggesting that the time‐varying covariate was associated with the CIF.…”

Letter: HCV complication and type 2 diabetes management—the directional link is not yet defined. Authors’ reply

“…4 It is clear from available research outcomes that HCV infection has a clear association with increased risk of T2D prevalence across various populations. [1][2][3][4] A cross-sectional study from Saudi Arabia (N = 300), investigating the association between the two conditions finds 8% and 2% respective prevalence of HCV among T2D and nondiabetics. 5 Multivariate regression analysis for the prevalence outcomes defines an increased prevalence of HCV infection in T2D patients.…”