Telomere shortening is a prognostic factor in chronic hepatitis C virus infection

Background & Aims: Telomere shortening limits the proliferative capacity of human cells to 50–70 cell divisions. In humans, telomere shortening occurs in most organs during aging and characterizes the end stage of chronic diseases, such as cirrhosis. A current concept indicates that dysfunctional telomeres limit the regenerative capacity of cells and organs by inducing DNA damage signals leading to cell cycle arrest (senescence) or apoptosis. It is currently unknown, whether telomere shortening is a prognostic marker in chronic liver disease.

Methods: Here we analyzed telomere length and p21 expression–a downstream target of telomere dysfunction signaling–in liver biopsies of 89 patients with chronic hepatitis C virus (HCV) infection. Clinical follow up data were available on 50 patients.

Results: At baseline, telomere shortening and p21 up-regulation correlated with hepatitis activity (p<0.001, p=0.001), liver fibrosis (p=0.001, p=0.013), and patientrsquor;s age (both p<0.001). The mean time of clinical follow up was 39.5 months. Disease progression (increase in MELD score ≥3, or increase in Child-Pugh score ≥2, or development of hepatocellular carcinoma) occurred in 5 patients and this correlated with shortened telomeres (p=0.03) and elevated p21 expression (p=0.0394). In Cox-regression multivariate analysis telomere shortening was most strongly associated with the disease progression (3.34-fold increase) among all other parameters that were tested including age, gender, and fibrosis score.

Conclusions: These findings provide the first evidence that telomere shortening is a prognostic marker for disease progression in chronic HCV infection.