Extrahepatic portal vein obstruction results in hepatocyte proliferation but a decrease in protein-C synthesis.
OBJECTIVE
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.
Chiu
Bill
B
Department of Surgery, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA.
Melin-Aldana
Hector
H
Pillai
Srikumar
S
Hernandez
Jose M
JM
Superina
Riccardo A
RA
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006975:Hypertension, Portal / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008026:Ligation; D008099:Liver / Q000098:blood supply / Q000166:cytology; D008111:Liver Function Tests; D011169:Portal Vein / Q000473:pathology; D011486:Protein C / Q000096:biosynthesis*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000098:blood supply
D011486:Protein C