Direct-acting antivirals (DAAs) are effective in treating chronic hepatitis C virus (HCV) infections. However, not all chronic hepatitis C complications seem to be fully curable following a sustained virologic response (SVR). The epigenetic clock’s definition of biological age acceleration has recently been linked to persistent viral infections. For a study, researchers sought to determine if biological age acceleration and epigenetic alterations were linked to chronic HCV infection and whether these changes may be reversed with SVR.

At 3 different times in time—the beginning of DAA treatment, the conclusion of treatment, and long-term follow-up(median 96 weeks after the end of treatment)—they included 54 well-characterized chronic hepatitis C patients who had achieved SVR following DAA therapy. Horvath’s clock was utilized to assess the epigenetic age acceleration (EAA) using the genome-wide DNA methylation status in peripheral blood mononuclear cells (PBMCs).

When compared to the age- and sex-matched reference group, those with HCV had an overall significant EAA of 3.12 years at baseline, as opposed to -2.61 years (P< 0.00003). All patient groups experienced a significant long-term increase in DNA methylation driven mostly by hypermethylated CpGs following HCV removal. At long-term follow-up, EAA accordingly dropped to 1.37 years. Only between the conclusion of therapy and follow-up was the drop in EAA statistically significant (P = 0.01). It was interesting to note that 8 people who got hepatocellular carcinoma after SVR had the greatest EAA and no signs of reversion.

The findings showed that HCV removal could result in “reverse inflammaging” and further knowledge of the biological effects of HCV eradication following DAA treatment. The potential utility of biological age as a biomarker for HCV sequelae following SVR was further supported by the results.

Reference: journal-of-hepatology.eu/article/S0168-8278(22)03115-4/fulltext