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Updated: May 27, 2025
Measurement of Liver Stiffness Using Atomic Force Microscopy Coupled with Polarization Microscopy
Published on: July 20, 2022
Influence of Cellular Aging on Liver Stiffness in Patients With Hepatitis C Virus Achieving Sustained Viral Response
Alejandro Gonzalez-Serna1,2,3,4, Anaïs Corma-Gomez1,3,4, Mercedes Cano2
1Grupo Virología e ITS, Hospital Universitario Virgen de Valme, Sevilla, Spain.
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.
Insights
Greater relative telomere length (RTL) is linked to reduced liver stiffness (LS) after hepatitis C virus (HCV) treatment. Cellular aging may impede liver regeneration even after successful HCV eradication.
Area of Science:
- Hepatology
- Virology
- Cellular Biology
Background:
- Hepatitis C virus (HCV) is a significant cause of liver disease.
- Direct-acting antivirals (DAAs) effectively eliminate HCV, leading to sustained viral response (SVR).
- However, 10%-30% of patients do not experience reduced liver stiffness (LS) post-SVR.
Purpose of the Study:
- To investigate the association between cellular aging markers and LS reduction in patients achieving SVR after HCV treatment.
- To identify factors contributing to the lack of LS improvement in a subset of patients post-HCV eradication.
Main Methods:
- Prospective cohort study (GEHEP-011) involving 175 patients undergoing DAA treatment.
- Measurement of cellular aging parameters (telomere length, mitochondrial function, senescence biomarkers) at DAA initiation.
- Assessment of LS decrease (≥20%) at SVR time point and its correlation with aging markers.
Main Results:
- Over 57% of patients achieved a significant (≥20%) LS reduction post-SVR.
- Greater relative telomere length (RTL) was the sole independent predictor of significant LS decrease in multivariate analysis (P = .047).
- LS changes (decrease, no change, or increase) were significantly associated with RTL (P = .011).
Conclusions:
- Increased relative telomere length (RTL) is independently associated with significant liver stiffness reduction post-SVR.
- Cellular aging, indicated by greater RTL, may hinder liver regeneration after successful HCV eradication.
- Further research is needed to understand the long-term impact of cellular aging on liver health post-SVR.
