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

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 under-went 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. (C) 2007 Elsevier Inc. All rights reserved.