Photo Credit: Alena Butusava

Cellular aging may explain persistent liver stiffness after HCV eradication, with shorter telomeres linked to poorer hepatic recovery despite viral clearance.

Researchers have implicated cellular aging as a contributing factor to the absence of liver regeneration following the eradication of hepatitis C virus (HCV) in some patients, according to results published in the Journal of Infectious Diseases.

As many as 10% to 30% of patients with HCV who achieve sustained viral response with direct-acting antivirals fail to see an improvement in liver stiffness, putting them at increased risk of comorbidities from persistent hepatic damage, according to the researchers. The mechanisms behind the lack of improvement, however, are not well understood.

This study investigated whether parameters associated with cellular aging were associated with liver stiffness in 175 patients with HCV who achieved sustained viral response. At initiation of direct-acting antiviral treatment, investigators measured cellular aging indicators in patients, including telomere attrition, mitochondrial alterations, and soluble biomarkers associated with senescence-associated secretory phenotype.

Among patients, 57.7% had a 20% or greater reduction in liver stiffness at the time of sustained viral response. The remaining 42.3% did not experience a significant decrease in liver stiffness, and some patients experienced an increase despite achieving sustained viral response after treatment.

Liver Stiffness & Telomere Length

In multivariate analysis adjusted for sex, age, and specific inflammatory markers, the sole variable independently associated with a significant decrease in liver stiffness was a longer relative telomere length, according to the findings.

While baseline liver stiffness did not differ among patients who experienced significant decrease in liver stiffness, those with a nonsignificant decrease in liver stiffness, and those with an increase in liver stiffness, the groups did differ in relative telomere length, the researchers reported. The group with a significant decrease in liver stiffness had the longest relative telomere length, while the group with increased liver stiffness had the shortest.

“Shorter telomeres are indicative of cellular aging and have been linked to increased inflammation and hepatocyte senescence,” the researchers wrote. “This reduction in relative telomere length in cell-free DNA may not only be related to increased inflammation and hepatocellular necrosis, which could affect liver regeneration in sustained viral response but could also have important implications for a higher likelihood of developing hepatocarcinoma.”

The team called for more studies to investigate the long-term effects of cellular aging in patients after HCV eradication.