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.

FIGURE 1

Flow chart of patient selection process. ACS: acute coronary syndrome; ESRD: end-stage renal disease; SVR: sustained virological response; TF: treatment failure; DAA: direct-acting antiviral; f/u: follow-up; y: year; IQR: inter-quartile range

FIGURE 2

Cumulative incidence function for acute coronary syndrome (ACS, A), end-stage renal disease (ESRD, B), ischemic stroke (C), and retinopathy (D) estimated by Kaplan-Meier estimates with death adjusted as a competing risk and stabilized inverse propensity weights for treatment imbalance. *The number of subjects at risk without weighting for competing risk and stabilized inverse propensity weights is provided for illustration purpose. Please see Table 2 for formal analysis.