Impact of direct-acting antivirals on leukocytic DNA telomere length in hepatitis C virus-related hepatic cirrhosis

Abstract

Background Direct-acting antiviral (DAAs) represent advancement in the management of hepatitis C virus (HCV)-related hepatic cirrhosis. A high proportion of patients achieve a sustained virologic response; eradication of HCV is coupled with a decreased risk of hepatocellular carcinoma. Recent evidence suggests that shortening of the DNA telomere may be linked to cellular senescence as well as predisposition to malignant transformation. Objective This study aimed to assess pretreatment leukocytic DNA telomere length in HCV-related cirrhosis and post viral eradication using DAAs. Patients and methods This study included 24 patients with HCV-related cirrhosis, Child–Pugh A. Whole-blood samples were obtained from patients before treatment and 12 weeks after the end of treatment, as well as from 24 healthy controls. Terminal restriction fragment, corresponding to telomere length, was measured using a nonradioactive Southern blot technique, detected by chemiluminescence. Results DNA telomere length was significantly shorter before treatment compared with 12 weeks after end of treatment in HCV-related cirrhotic patients. Also, it was significantly shorter in patients before treatment compared with healthy individuals. Conclusion Telomere elongation in blood leukocytes can be considered a marker of recovery of inflammation after DAAs-induced HCV eradication. Still, the possibility of activation by cancer initiation cannot be excluded.

Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals

“…Another remarkable finding was the significant increase in RTL values after HCV eradication with DAAs that was found in HIV/HCV-coinfected patients only. However, a recent study of 24 HCV-monoinfected patients on DAA therapy described a significant telomere elongation in PBMCs 12 weeks after completing HCV treatment [21]. Our HCV-monoinfected patients only showed a slight upward trend in telomere size after HCV therapy that was not significant, probably due to the small sample size at 48 weeks after completing HCV treatment.…”

Difference in Relative Telomere Length Between Sudanese and Chinese Individuals

“…The role of telomeres has been further described and studied because telomeres have been implicated in numerous diseases, such as cardiovascular diseases, acute kidney injury, and carcinogenesis (28)(29)(30)(31)(32)(33). In addition, the shortened length of telomeres has been clearly observed in various human diseases, such as aplastic anemia, hepatic disease, and pulmonary fibrosis (34)(35)(36)(37). Other diseases are also associated with a mutation in genes encoding telomere proteins (38,39).…”