Sustained Virological Response to Hepatitis C Treatment Decreases the Incidence of Complications Associated With Type 2 Diabetes

Jia Li; Stuart C. Gordon; Loralee B. Rupp; Talan Zhang; Sheri Trudeau; Scott D. Holmberg; Anne C. Moorman; Philip R. Spradling; Eyasu H. Teshale; Joseph A. Boscarino; Mark A. Schmidt; Yihe G. Daida; Mei Lu; for the CHeCS Investigators


Aliment Pharmacol Ther. 2019;49(5):599-608. 

In This Article

Abstract and Introduction


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 relationship between hepatitis C (HCV) infection and type 2 diabetes (T2D) is complex. Both chronic HCV itself and HCV-related cirrhosis may increase risk for the subsequent development of type 2 diabetes, while existing diabetes appears to accelerate the progression of chronic HCV infection toward cirrhosis.[1,2,3,4] Antiviral treatment introduces a further layer of complexity; interferon-based therapies, for example, have been implicated as a mediator for development of type 2 diabetes.[5] We recently observed that sustained virological response (SVR) to antiviral treatment, among nondiabetics, reduced the subsequent incidence of diabetes.[6]

Despite strong evidence of the intricate interrelationship between HCV and type 2 diabetes, the impact of antiviral treatment status and outcome on various long-term diabetes-related complications among HCV patients remains largely unknown. A single study from Taiwan demonstrated that treatment with pegylated interferon improved renal and cardiovascular outcomes among HCV patients with diabetes.[7] However, this study was limited by a lack of data regarding newer, direct-acting antiviral (DAA) therapies and treatment outcomes; it is also unclear whether these results are generalisable to other demographic groups. There remain no published reports regarding the impact of successful antiviral treatment—particularly DAAs—on risk of acute coronary syndrome (ACS), end-stage renal disease (ESRD), ischaemic stroke, or retinopathy among diabetic HCV patients in the United States.

Using comprehensive longitudinal electronic health record-based data from the geographically- and racially-diverse Chronic Hepatitis Cohort Study (CHeCS)—which includes over 10 000 HCV patients drawn from four large health systems in the United States—we investigated the impact of HCV treatment status and outcome on long-term complications of T2D.