Extrahepatic portal vein obstruction results in hepatocyte proliferation but a decrease in protein-C synthesis

Bill Chiu, Hector Melin-Aldana, Srikumar Pillai, Jose M. Hernandez, Riccardo A Superina*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: Extrahepatic portal vein obstruction (EHPVO) results in decreased levels of liver-dependent coagulation factors in children. We developed a rat model to test the hypothesis that lower factor levels associated with EHPVO were from diminished synthesis rather than increased consumption. Methods: A total of 8 rats (experimental group) underwent narrowing of portal vein (PV) and 8 underwent sham operations. Liver and spleen mass, serum alanine aminotransferase, bilirubin, ammonia, prothrombin time, factor VII, and protein-C were measured before and 3 months after PV narrowing. Hepatocyte proliferation and apoptosis were quantified using Ki-67 and TUNEL assays. Results: Portal vein diameter was 71% ± 13% narrower in experimental animals. Liver mass was unchanged, but proportional spleen mass was higher in the experimental group at 3 months (0.31% ± 0.05% vs 0.26% ± 0.04%; P < .05). Percent apoptotic cells at 3 months was similar in both groups (0.14% ± 0.08% vs 0.13% ± 0.07%), but percent proliferating cells was higher in the experimental group (0.63% ± 0.17% vs 0.34% ± 0.11%; P < .05). Three-month protein-C levels decreased significantly only in the experimental group compared with preoperative values (12.8% ± 4.4% vs 7.6% ± 5.1%; P < .05). Changes in other parameters were not significant. Conclusions: Our EHPVO model consistently produced PV narrowing. The increase in hepatocyte proliferation seen after EHPVO suggests a liver repair response that is insufficient to maintain normal protein-C synthesis and serum levels.

Original languageEnglish (US)
Pages (from-to)796-799
Number of pages4
JournalJournal of Pediatric Surgery
Volume42
Issue number5
DOIs
StatePublished - Jul 1 2007

Fingerprint

Portal Vein
Protein C
Hepatocytes
Liver
Spleen
Factor VII
Blood Coagulation Factors
Prothrombin Time
In Situ Nick-End Labeling
Serum
Alanine Transaminase
Bilirubin
Ammonia
Apoptosis

Keywords

  • Coagulation factor
  • Hepatocyte proliferation
  • Portal vein

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery

Cite this

@article{3b154d2f6fce4370b9fc0aa77c626825,
title = "Extrahepatic portal vein obstruction results in hepatocyte proliferation but a decrease in protein-C synthesis",
abstract = "Purpose: Extrahepatic portal vein obstruction (EHPVO) results in decreased levels of liver-dependent coagulation factors in children. We developed a rat model to test the hypothesis that lower factor levels associated with EHPVO were from diminished synthesis rather than increased consumption. Methods: A total of 8 rats (experimental group) underwent narrowing of portal vein (PV) and 8 underwent sham operations. Liver and spleen mass, serum alanine aminotransferase, bilirubin, ammonia, prothrombin time, factor VII, and protein-C were measured before and 3 months after PV narrowing. Hepatocyte proliferation and apoptosis were quantified using Ki-67 and TUNEL assays. Results: Portal vein diameter was 71{\%} ± 13{\%} narrower in experimental animals. Liver mass was unchanged, but proportional spleen mass was higher in the experimental group at 3 months (0.31{\%} ± 0.05{\%} vs 0.26{\%} ± 0.04{\%}; P < .05). Percent apoptotic cells at 3 months was similar in both groups (0.14{\%} ± 0.08{\%} vs 0.13{\%} ± 0.07{\%}), but percent proliferating cells was higher in the experimental group (0.63{\%} ± 0.17{\%} vs 0.34{\%} ± 0.11{\%}; P < .05). Three-month protein-C levels decreased significantly only in the experimental group compared with preoperative values (12.8{\%} ± 4.4{\%} vs 7.6{\%} ± 5.1{\%}; P < .05). Changes in other parameters were not significant. Conclusions: Our EHPVO model consistently produced PV narrowing. The increase in hepatocyte proliferation seen after EHPVO suggests a liver repair response that is insufficient to maintain normal protein-C synthesis and serum levels.",
keywords = "Coagulation factor, Hepatocyte proliferation, Portal vein",
author = "Bill Chiu and Hector Melin-Aldana and Srikumar Pillai and Hernandez, {Jose M.} and Superina, {Riccardo A}",
year = "2007",
month = "7",
day = "1",
doi = "10.1016/j.jpedsurg.2006.12.063",
language = "English (US)",
volume = "42",
pages = "796--799",
journal = "Journal of Pediatric Surgery",
issn = "0022-3468",
publisher = "W.B. Saunders Ltd",
number = "5",

}

Extrahepatic portal vein obstruction results in hepatocyte proliferation but a decrease in protein-C synthesis. / Chiu, Bill; Melin-Aldana, Hector; Pillai, Srikumar; Hernandez, Jose M.; Superina, Riccardo A.

In: Journal of Pediatric Surgery, Vol. 42, No. 5, 01.07.2007, p. 796-799.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Extrahepatic portal vein obstruction results in hepatocyte proliferation but a decrease in protein-C synthesis

AU - Chiu, Bill

AU - Melin-Aldana, Hector

AU - Pillai, Srikumar

AU - Hernandez, Jose M.

AU - Superina, Riccardo A

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Purpose: Extrahepatic portal vein obstruction (EHPVO) results in decreased levels of liver-dependent coagulation factors in children. We developed a rat model to test the hypothesis that lower factor levels associated with EHPVO were from diminished synthesis rather than increased consumption. Methods: A total of 8 rats (experimental group) underwent narrowing of portal vein (PV) and 8 underwent sham operations. Liver and spleen mass, serum alanine aminotransferase, bilirubin, ammonia, prothrombin time, factor VII, and protein-C were measured before and 3 months after PV narrowing. Hepatocyte proliferation and apoptosis were quantified using Ki-67 and TUNEL assays. Results: Portal vein diameter was 71% ± 13% narrower in experimental animals. Liver mass was unchanged, but proportional spleen mass was higher in the experimental group at 3 months (0.31% ± 0.05% vs 0.26% ± 0.04%; P < .05). Percent apoptotic cells at 3 months was similar in both groups (0.14% ± 0.08% vs 0.13% ± 0.07%), but percent proliferating cells was higher in the experimental group (0.63% ± 0.17% vs 0.34% ± 0.11%; P < .05). Three-month protein-C levels decreased significantly only in the experimental group compared with preoperative values (12.8% ± 4.4% vs 7.6% ± 5.1%; P < .05). Changes in other parameters were not significant. Conclusions: Our EHPVO model consistently produced PV narrowing. The increase in hepatocyte proliferation seen after EHPVO suggests a liver repair response that is insufficient to maintain normal protein-C synthesis and serum levels.

AB - Purpose: Extrahepatic portal vein obstruction (EHPVO) results in decreased levels of liver-dependent coagulation factors in children. We developed a rat model to test the hypothesis that lower factor levels associated with EHPVO were from diminished synthesis rather than increased consumption. Methods: A total of 8 rats (experimental group) underwent narrowing of portal vein (PV) and 8 underwent sham operations. Liver and spleen mass, serum alanine aminotransferase, bilirubin, ammonia, prothrombin time, factor VII, and protein-C were measured before and 3 months after PV narrowing. Hepatocyte proliferation and apoptosis were quantified using Ki-67 and TUNEL assays. Results: Portal vein diameter was 71% ± 13% narrower in experimental animals. Liver mass was unchanged, but proportional spleen mass was higher in the experimental group at 3 months (0.31% ± 0.05% vs 0.26% ± 0.04%; P < .05). Percent apoptotic cells at 3 months was similar in both groups (0.14% ± 0.08% vs 0.13% ± 0.07%), but percent proliferating cells was higher in the experimental group (0.63% ± 0.17% vs 0.34% ± 0.11%; P < .05). Three-month protein-C levels decreased significantly only in the experimental group compared with preoperative values (12.8% ± 4.4% vs 7.6% ± 5.1%; P < .05). Changes in other parameters were not significant. Conclusions: Our EHPVO model consistently produced PV narrowing. The increase in hepatocyte proliferation seen after EHPVO suggests a liver repair response that is insufficient to maintain normal protein-C synthesis and serum levels.

KW - Coagulation factor

KW - Hepatocyte proliferation

KW - Portal vein

UR - http://www.scopus.com/inward/record.url?scp=34248219173&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248219173&partnerID=8YFLogxK

U2 - 10.1016/j.jpedsurg.2006.12.063

DO - 10.1016/j.jpedsurg.2006.12.063

M3 - Article

VL - 42

SP - 796

EP - 799

JO - Journal of Pediatric Surgery

JF - Journal of Pediatric Surgery

SN - 0022-3468

IS - 5

ER -