1 VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
2 Weill Cornell Medical College, New York, NY, USA and Doha, Qatar.
3 Hamad Medical Corporation, Doha, Qatar.
Effect of interferon-based therapies for HCV upon risk of diabetes is controversial. Effect of newer directly acting antiviral agents (DAA) upon this risk is unknown. We sought to determine the effect of HCV treatment upon the risk and incidence of diabetes.
Using the ERCHIVES database for persons with chronic HCV infection (n=242,680), we identified those treated with a pegylated interferon and ribavirin regimen (PEG/RBV, n=4764) or a DAA-containing regimen (21,279), after excluding those with diabetes at baseline, HIV or hepatitis B virus coinfection and those treated with both PEG/RBV and DAA regimens. Age/race/sex/propensity score matched controls (1:1) were also identified.
Diabetes incidence rates/1,000 person-years [95% CI] were 20.6(19.6,21.6) among untreated, 19.8[18.3,21.4] among PEG/RBV and 9.89[8.7,11.1] among DAA treated persons (P<0.001). Among the treated, rates were 13.3[12.2,14.5] for those with SVR and 19.2[17.4,21.1] for those without SVR (P<0.0001). A larger reduction was observed in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for FIB-4<1.25; 5.7 for FIB-4 1.26-3.25; 9.8 for FIB-4>3.25). DAA treatment (HR 0.53, 95%CI 0.46,0.63) and SVR (HR 0.81, 95%CI 0.70,0.93) were associated with a significantly reduced risk of diabetes. DAA treated persons had longer diabetes free survival compared to untreated and PEG/RBV treated persons. There was no significant difference in diabetes free survival between untreated and PEG/RBV treated persons. Results were similar in inverse probability of treatment and censoring weight models.
DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefit is more pronounced in persons with more advanced liver fibrosis.