Hepatocellular telomere length in biliary atresia measured by Q-FISH.
BACKGROUND
Liver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity.


METHODS
Hepatic tissues were obtained from 20 patients with biliary atresia who underwent LT and 10 age-matched autopsied individuals (mean age, 1.7 and 1.2 years, respectively). Telomere lengths were measured by Southern blotting and quantitative fluorescence in situ hybridization using the normalized telomere-centromere ratio. The correlation between the normalized telomere-centromere ratio for the hepatocytes in biliary atresia and the pediatric end-stage liver disease score was analyzed.


RESULTS
The median terminal restriction fragment length of the hepatic tissues in biliary atresia was not significantly different from that of the control (p = 0.425), whereas the median normalized telomere-centromere ratio of hepatocytes in biliary atresia was significantly smaller than that of the control (p < 0.001). Regression analysis demonstrated a negative correlation of the normalized telomere-centromere ratio with the pediatric end-stage liver disease score in biliary atresia (p < 0.001).


CONCLUSIONS
Telomere length analysis using quantitative fluorescence in situ hybridization could be an objective indicator of hepatocellular reserve capacity in patients with biliary atresia, and excessive telomere shortening supports the early implementation of liver transplantation.
Department of Transplant Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke City, Tochigi, 329-0498, Japan. yuki371@jichi.ac.jp
Yukihiro
Y
Sanada
Junko
J
Aida
Youichi
Y
Kawano
Ken-ichi
K
Nakamura
Naotaka
N
Shimomura
Naoshi
N
Ishikawa
Tomio
T
Arai
Steven S S
SS
Poon
Naoya
N
Yamada
Noriki
N
Okada
Taiichi
T
Wakiya
Makoto
M
Hayashida
Takeshi
T
Saito
Satoshi
S
Egami
Shuji
S
Hishikawa
Yoshiyuki
Y
Ihara
Taizen
T
Urahashi
Koichi
K
Mizuta
Yoshikazu
Y
Yasuda
Hideo
H
Kawarasaki
Kaiyo
K
Takubo
D001656:Biliary Atresia / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D002648:Child; D002675:Child, Preschool; D005260:Female; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008099:Liver / Q000473:pathology*; D016031:Liver Transplantation; D008297:Male; D059506:Telomere Shortening