DNA Methylation and Immune Cell Markers Demonstrate Evidence of Accelerated Aging in Patients with Chronic HBV or HCV, with or without HIV Co-Infection.

BACKGROUND Several chronic diseases have been shown to accelerate biological aging. We investigated age acceleration and the association between peripheral blood DNAm and immune cell markers in patients chronically infected with the hepatitis B virus (HBV) or the hepatitis C virus (HCV) with and without human immunodeficiency virus (HIV) co-infection. METHODS Age acceleration was measured as the difference between epigenetic age (Horvath clock) and chronological age. The immune marker model of age acceleration was developed using Elastic Net regression to select both the immune markers and their associated weights in the final linear model. RESULTS Patients with chronic HBV (n=51) had a significantly higher median epigenetic age compared to chronological age (age accelerated) (p < 0.001). In patients with chronic HCV infection (n=63), age acceleration was associated with liver fibrosis as assessed by histology (p < 0.05), or presence of HIV co-infection (p < 0.05), but not HCV mono-infection. Age acceleration defined by immune markers was concordant with age acceleration by DNA methylation (correlation coefficient=0.59 in HBV; p=0.0025). One-year treatment of HBV patients with nucleoside therapy was associated with a modest reduction in age acceleration as measured using the immune marker model (-0.65 years, p=0.018). CONCLUSION Our findings suggest that patients with chronic viral hepatitis have accelerated epigenetic aging and that immune markers defines biological age and has the potential to assess the effects of therapeutic intervention on age acceleration.