Influence of Cellular Aging on Liver Stiffness in HCV Patients Achieving Sustained Viral Response.

Abstract

Background: Liver stiffness (LS) is not reduced in 10-30% of patients who achieve sustained viral response (SVR) after HCV elimination with direct-acting antivirals (DAA). Our aim was to analyze whether the parameters associated with cellular aging measured at the DAA initiation date are related to LS reduction upon achieving SVR.

Methods: Prospective cohort study (GEHEP-011; clinicaltrials.gov ID: NCT04460157). We measured several parameters associated with cellular aging, such as telomere attrition, mitochondrial alterations, and soluble biomarkers associated with Senescence-Associated Secretory Phenotype (SASP) at the DAA initiation date, and examined their associations with a significant (≥20%) LS decrease at the SVR time point.

Results: In total, 175 individuals were included in this study. In 101 (57.7%) patients, the LS reduction was ≥20% at SVR. In the multivariate analysis adjusted for sex, age, CXCL10, hsPCR, and CCL11 levels, greater relative telomere length (RTL) emerged as the sole variable independently associated with a significant LS decrease in SVR (95% CI, 1.102 (1.001-1.1214), p=0.047). Furthermore, changes in LS, including significant decreases and decreases of <20% or increases, were congruently associated with RTL (p=0.011).

Conclusions: Greater RTL was independently associated with a significant LS reduction in SVR. Thus, increased cellular aging may be responsible for the absence of liver regeneration after HCV eradication. Further studies are required to assess the long-term effects of cellular aging after SVR.