TY - JOUR
T1 - Telomere length, aggregates, and capture in cirrhosis
AU - Laish, Ido
AU - Mari, Amir
AU - Mannasse, Batya
AU - Hadary, Ruth
AU - Konikoff, Fred Meir
AU - Amiel, Aliza
AU - Kitay-Cohen, Yona
N1 - Publisher Copyright:
© 2018, Israel Medical Association. All rights reserved.
PY - 2018/5
Y1 - 2018/5
N2 - Background: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules. Objectives: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology. Methods: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2–5, 6–10, and 11–15 telomeres, relative to the size of a single telomere. Results: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group. Conclusions: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.
AB - Background: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules. Objectives: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology. Methods: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2–5, 6–10, and 11–15 telomeres, relative to the size of a single telomere. Results: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group. Conclusions: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.
KW - Cirrhosis
KW - Telomere aggregates
KW - Telomere length
KW - Telomeres
KW - Viral hepatitis
UR - http://www.scopus.com/inward/record.url?scp=85047119185&partnerID=8YFLogxK
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AN - SCOPUS:85047119185
SN - 1565-1088
VL - 20
SP - 295
EP - 299
JO - Israel Medical Association Journal
JF - Israel Medical Association Journal
IS - 5
ER -