Terlipressin Effect of Portal Pressure Control on Liver Regeneration in 90% Hepatectomized Rats

PURPOSE: Liver regeneration is crucial following major liver resection or partial liver transplantation. The inhibition mechanism of regeneration is portal hypertension caused by excessive portal flow to the small liver. Portal hypertension can be controlled with terlipressin, an effective splanchnic vasoconstrictor. The purpose of this study was to investigate the effect of terlipressin on the portal pressure and liver regeneration in 90% hepatectomized rats. METHODS: Forty-eight male Sprague-Dawley (250 gm) rats were divided into three groups; Group N (n=16) underwent Sham operation, Group C (n=16) was injected with 0.1 mL saline after 90% hepatectomy, and Group T (n=16) was injected with 50microgram/kg terlipressin after 90% hepatectomy. To assess the liver regeneration response, the changes in proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNFalpha) were monitored for 48 hours. RESULTS: The baseline portal pressures in Groups N, C, and T were 4.9, 12.4, and 14.1 mmHg (P<0.05). In Group T, the injection of terlipressin induced a significant reduction of the portal pressure (-30.2%, P<0.05). There was no difference in PCNA between Groups C and T. However, serum TNFalpha levels were significantly higher in Group T (248.4 pg/ mL) than Group C (52.3 pg/mL) 48 hours postoperatively (P<0.05). CONCLUSION: The control of portal pressure with the use of terlipressin was correlated with serum TNFalpha. These data provide evidence that the administration of terlipressin during the early postoperative period following major liver resection may have an attenuating effect on portal hypertension, which may also stimulate the initiation of the regenerative process.

Isolation and Culture of Pig Hepatocyte in Large Scale for the Application of Bioartificial Liver System / 대한간학회지

BACKGROUND/AIMS: Acute hepatic failure is a serious problem. Its mortality reaches up to 80%. Only liver transplantation has been accepted as a definite treatment for patients with hepatic failure but shortage of donor organs is the main obstacle of this approach. A possible solution to this problem is a bioartificial liver system, perfusion of patients blood to isolated hepatocyte. In this study, we performed the isolation and culture of pig hepatocyte in large scale for the application of bioartificial liver system. METHODS: Hepatocyte isolation was performed by two-step collagenase method via portal vein perfusion in 10kg female pigs. After that, we compared the functional differences of the spheroid culture to the monolayer culture of hepatocyte. The viability and the function of hepatocyte were assessed using trypan-blue exclusion test and the measurement of the rate of ureagenesis and ammonia removal. RESULTS: The average viability and yield of hepatocyte were 86.8 +/- 8.0 % and 7.8 +/- 5.4 X 10(9), respectively. The spheroid culture was superior to the monolayer culture in functional aspect of hepatocyte, and their differences, especially for ammonia removal, were more apparent in parallel with culture time. CONCLUSIONS: For hepatocyte isolation, we obtained sufficient viability and yield of hepatocyte for clinical usage of bioartificial liver system. The function of hepatocyte seems to be better in the spheroid culture than in the monolayer culture. Further studies are needed for application of bioartificial liver system in clinical setting.