Hepatocellular telomere length in biliary atresia measured by Q-FISH.

Abstract

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.

• Authors: Yukihiro Sanada, Junko Aida, Youichi Kawano, Ken-ichi Nakamura, Naotaka Shimomura, Naoshi Ishikawa, Tomio Arai, Steven S S Poon, Naoya Yamada, Noriki Okada, Taiichi Wakiya, Makoto Hayashida, Takeshi Saito, Satoshi Egami, Shuji Hishikawa, Yoshiyuki Ihara, Taizen Urahashi, Koichi Mizuta, Yoshikazu Yasuda, Hideo Kawarasaki, Kaiyo Takubo
• Journal: World journal of surgery (World J Surg) Vol. 36 Issue 4 Pg. 908-16 (Apr 2012) ISSN: 1432-2323 [Electronic] United States
• PMID: 22311140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Biliary Atresia (genetics, pathology, surgery)
• Child
• Child, Preschool
• Female
• Hepatocytes (pathology)
• Humans
• In Situ Hybridization, Fluorescence
• Infant
• Liver (pathology)
• Liver Transplantation
• Male
• Telomere Shortening