Influence of Cellular Aging on Liver Stiffness in Patients With Hepatitis C Virus Achieving Sustained Viral Response.

BACKGROUND

Liver stiffness (LS) is not reduced in 10%-30% of patients who achieve sustained viral response (SVR) after hepatitis C virus (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

In a prospective cohort study (GEHEP-011) we measured several parameters associated with cellular aging, such as telomere attrition, mitochondrial alterations, and soluble biomarkers associated with senescence-associated secretory phenotype 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 (1.102; 95% confidence interval, 1.001-1.1214; P = .047). Furthermore, changes in LS, including significant decrease, decrease <20%, or increase, were congruently associated with RTL (P = .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.

CLINICAL TRIALS REGISTRATION: NCT04460157.