Objective To establish the rat orthotopic liver transplantation model by characterizing the blood supply of hepatic artery with the Cuff skill and the modified arterial sleeve anastomosis, to explore the possible mechanisms of acute rejection and the express of Fractalkine (Fkn) in the early stage after hepatic allograft operation. Methods SD rats were selected as donors and Wistar rats as receptor for the rejection model of orthotopic liver transplantation. Recipient rats were divided into 2 groups randomly after operationand the drugs were given intraperitoneally once a day in each group. In the experimental group, cyclosporine A (CsA) was delivered with 3 mg/kg. In the control group, only normal saline was given with 3 ml/kg. Condition of survivals were observed. The rejection actvity index (RAI) and the expression of Fkn of liver tissue were observed after 3rd, 5th and 7th days in 5 rats. The rest of rats in each group were fed and given drug or normal saline until they were died and the mean survival time were recorded. Results There were 18 survivals in control group, and 19 in experimental group after liver transplantation. Condition of survivals in experimental group was better than that of control group. The mean survival times of experimental group(19.50±4.51 days) was significantly longer than that of control group(7.60±1.60 days), showing statistically significant difference (P＜0.05). After 3rd, 5th and 7th days of transplantation, RAI of control group were 3.80±0.35,5.90±0.87 and 7.50±1.30,respectively;RAI of experimental group were 3.10±0.21,3.90±0.41 and 4.50±0.52.Therewasstatistically significant difference in RAI between 2 groups on the 7th day after transplantation (Plt;0.01). On the 3rd,5th and 7th days after transplantation, the Fkn of control group was 8.20±0.57,21.30±3.30 and 25.70±4.91, and that of experimental group was 8.30±0.56,10.30±0.67 and 11.70±1.23. There were statistically significant differences in Fkn between 2 groups on the 5th, 7th days after transplantation (Plt;0.01). Conclusion Fkn is a participant inacute rejection after the rat orthotopic liver transplantation and can be chosen as a useful target in the diagnosis of acute rejection. CsA has immunosuppressive property in the condition of acute rejection in the rat orthotopic liver transplantation, which may be result from the decreased the level of Fkn.
Objective To observe the expression of heat shock protein 70 (HSP70) in human liver after hepatic transplantation, and to study its correlation with the occurrence and progression of acute allograft rejection.Methods Fifteen biopsy specimen of allograft liver after transplantation were collected and divided into three groups according to their pathological changes: control group (no rejection), mild acute rejection group, and moderate/serious acute rejection group. The expressions of HSP70 in grafts were detected by using immunohistochemical method and imaging analysis. Results HSP70 was expressed in all 3 groups, and appeared mainly in hepatocellular cytoplasm. The immunohistochemical imaging analysis of HSP70 showed: integral optical density (IOD) which was 30.99±11.14 in the control group was lower than that in the mild acute rejection group (68.84±21.37) and that in the moderate/serious acute rejection group (71.82±19.99), P＜0.01； and the IOD in the moderate/serious acute rejection group was higher than that in the mild acute rejection group (P＜0.05). Conclusion HSP70 plays a role in cellular protection for allograft liver, and the continuously increasing expression of HSP70 in graft maybe closely relates to the occurrence and progression of acute allograft rejection.
Objective To review the advances of livingrelated liver transplantation for children. MethodsOn the basis of the data in Kyoto university, the center of livingrelated liver transplantation in the world, the current situation of livingrelated liver transplantation for children were investigated. ResultsEighty percent of patients who underwent the livingrelated liver transplantation were children with cholestatic liver disease. From the data of 462 cases, the patients’survival rate for 1, 3 and 5 years after livingrelated liver transplantation (79.8%, 77.0% and 77.0% respectively) preceded the survival rate of 129 patients who underwent the whole liver transplantation (76.0%, 70.0% and 65.0% respectively). To the livingrelated liver transplantation, the survival rate was higher for patients who underwent selective operation (85.0%) than emergency surgery (67.0%). The principal causes of death were rejection and infection. Furthermore, a partial orthotopic liver transplantation and livingrelated liver replantation were performed for children. Conclusion Strict indication, optimal health status and perfect postoperative management are the keys to keep patients longterm healthy survival. The curative effect of livingrelated liver transplantation precedes the whole liver transplantation. For children, livingrelated liver transplantation is better than for adults.
Objective To study the effect of Huaier granule on the recurrence and metastasis of hepatocellular carcinoma (HCC) and immune rejection in the postoperative patients with liver transplantation for HCC. Methods Twenty-eight patients of liver transplantation for HCC who had taken Huaier granule orally for more than 6 months from September 2001 to March 2007 in West China Hospital were included as treatment group, and other 56 patients of liver transplantation for HCC who didn’t take any Huaier granule in the same time were included as the control group according to the same stage of TNM, degree of tumor differentiation (Edmondson grading) respectively with the treatment group. The method of retrospective cohort study was used to compare the incidence of immune rejection and the 6-month, 1-year, and 2-year recurrence and metastasis of HCC, disease free survival rate, and survival rate between two groups after 2 years’ follow-up beginning from the date of surgery. Results The 6-month, 1-year, and 2-year tumor recurrence and metastasis incidences in treatment group were 14.3%, 32.1%, and 39.3% respectively, which were 23.2%, 32.1%, and 50.0% respectively in control group, and the 2-year tumor recurrence and metastasis incidence of the treatment group was lower than that of the control group. The 6-month, 1-year, and 2-year disease free survival rates in treatment group were 85.7%, 67.5%, and 60.0% respectively, which were 76.7%, 67.6%, and 49.3% respectively in control group, and the 2-year disease free survival rate of treatment group was higher than that of the control group. The 6-month, 1-year, 2-year survival rates in treatment group were 92.9%, 78.6%, and 67.9% respectively, which were 89.3%, 75.0%, and 62.5% respectively in control group. But the 2-year tumor recurrence and metastasis incidence (P=0.353), 2-year disease free survival curve (P=0.386), and 2-year survival curve (P=0.620) were not significantly different between two groups. The incidence of immune rejection was 14.29% in the treatment group and 16.07% in the control group, which was not significantly different between the two groups (P=0.831). Conclusions Huaier granule can increase the 2-year tumor-free survival rate and restrain the recurrence and metastasis of HCC, and does not increase the incidence of immune rejection. Huaier granule as a treatment of HCC in patients with liver transplantation is safe and effective.
Objective To observe the changes of blood biochemistry during orthotopic liver transplantation in pigs. Methods Fourteen healthy pigs were anesthetized and intubated, the right carotic artery was cannulated for blood pressure monitoring and blood biochemical sampling. The right internal jugular vein was cannulated for central venous pressure monitoring. No exogenous glucose was administrated during operation, the donor liver was perfused with Collin’s solution. During the anhepatic stage, the veno-venous bypass was established, blood was pumped from the portal and femoral veins using an extracorporeal circuit, and returned to the axillary vein. The arterial blood was sampled for monitoring arterial blood gas tensions, Na＋,K＋,Ca2＋, and blood glucose levels.Results During preanhepatic stage, blood glucose levels increased progressively, blood electrolytes and acidbase balance were stable. During anhepatic stage, pH was decreased, base deficit was increased significantly, blood glucose levels were significantly decreased, blood electrolytes were stable. During neohepatic stage, acidosis became more severe, blood potassium increased abruptly on reperfusin of the grafted liver, blood glucose was higher than that in prehepatic and anhepatic stage. Conclusion During operation of liver transplantation, metabolic acidosis developed progressively, blood glucose decreased in anhepatic stage, blood glucose and potassium increased significantly on reperfusion of the grafted liver.
ObjectiveTo investigate pathological changes of liver and risk factors for hepatic injury after trauma, in order to provide the instructions for clinical liver transplantation and accumulate the pathological data. MethodsWe retrospectively analyzed the clinical data of 142 patients who died after trauma between January 2010 and December 2014. Based on whether the patients had acute liver damage before dying, they were divided into two groups. The observation group had liver damage before dying, while the control group had not. Combined with the details of trauma, clinical data and autopsy results, we statistically analyzed the pathological changes of liver and risk factors for acute liver damage, including age, gender, trauma kind, trauma site, interval between trauma and hospitalization, damage degree, length of hypotension, the use of more than two vasopressors, large amount of blood transfusion, and complication of shock, infection, or underlying diseases. According to injury severity score (ISS) system, the damage degree was divided into mild damage (ISS<16), moderate damage (ISS≥16 and<25), and severe damage (ISS≥25). ResultsAmong the 142 patients, there were 45 in the observation group with varying degrees of liver cell necrosis, among whom there were 8 mild cases, 14 moderate and 23 severe. There were 97 patients in the control group without acute liver damage, and no significant changes were found in their hepatic tissue. Liver damage was not correlated with age, gender, damage kind, damage site, or pre-hospital time (P>0.05), while it was corrected with the degree of damage, time of hypotension (≥0.5 hour), the use of more than two vasopressors, large amount of blood transfusion (2 000 mL/24 hours), and combination of shock, infection, and other disease except for cardiac and pulmonary diseases (P<0.05). ConclusionWhen using donor livers from patients dying from trauma for transplantation, physicians should be alert to the factors discussed previously which can increase the risk of hepatic injury. Biopsy is useful to assess the suitability of donor livers prior to transplantation.
Objective To establish a reliable rats model of orthotopic liver transplantation with non-heart beating donors. Methods The model was established with modified double-cuff method. According to obtain pre-liver warm ischemia time experiencing non-heart-beat the rats were divided into 3 groups: 10 min (R10 group), 20 min (R20 group) and 30 min (R30 group), then one week survival after operation was compared in rats. Results The operative time of donor was 30 min approximately except warm ischemia time and the cold preservation time of donor liver was 1 h. The anastomotic time for suprahepatic vena cava was 12-22 min (mean 15 min). The anastomotic time for portal vein and infrahepatic vena cava was about 2 min and 1 min, respectively. The anhepatic phase sustained 14-24 min (mean 19 min). The operative time of receptor was 50-65 min (mean 60 min). Twelve rats died at 24 h after operation, which was considered as operative failure. The success rates of operation in R10 group, R20 group, and R30 group were 95% (19/20), 80% (16/20), and 65% (13/20), respectively. After one week the survival rate was 95% (18/19), 81% (13/16), and 54% (7/13), respectively. Conclusions Improved non-heart donor liver transplantation model of rat on the basis of Kamada’s “twocuff technique” acts as a good simulation in clinical non-heart-donor liver transplantation. This study showes that rat liver can tolerate warm ischemia time less than 30 min, the short-term survival after transplantation can reach satisfactory results. However, long-term survival requires further study.
Objective To Investigate the indications, surgical technique and perioperative management of orthotopic liver transplantation.Methods Orthotopic liver transplantation was successfully performed on a unresectable liver cancer on caudate lobe, 2 cases with Caroli’s disease and 7 cases with advanced liver cirrohosis. A 11 year’s old girl with Caroli’s disease was performed on one reduced size liver transplantation (RSLT). Results The recovery of liver graft function was good after the operation in those patients without perioperative death. The case of liver cancer died of recurrent cancer on the 139th postoperative day, 1 case died of severe fungus infection and one died of gastric stress ulcer perforation, other 7 cases recovered well without complications. Conclusion The results suggest that unresectable central liver cancer, terminal liver cirrohosis or benign liver diseases combined with severe liver disfunction are good indications for liver transplantation. Good surgical technique and perioperative management are key points to succucess of the liver transplantation.
ObjectiveTo evaluate the effect of pre-infusion of allogeneic lymphoyctes treated with 5-FU on the rat liver graft. MethodsRat liver transplant models from Wistar to SD were established. Four groups were designed as following: control group: only liver transplantation without any other intervention; lymphocytes group: 1 ml of untreated lymphocytes (5×106/ml) from Wistar rats were preinfused into SD rats on day 7 and 4 separately before transplantation; lymphocytes with low concentration of 5-FU group: low concentration 5-FU (7.5 μg) treated lymphocytes were preinfused as above; lymphocytes with high concentration of 5-FU group: high concentration 5-FU (15 μg) treated lymphocytes were preinfused as above. Fas-L and CD8 expression were detected by immunohistochemistry method on day 7 after transplantation. ResultsThe integral opticaldensity (IOD) of Fas-L positive lymphocytes in the lobules of liver and portal areas were higher in lymphocytes with low concentration of 5-FU group than in the other groups （Plt;0.05）. There was no difference between lymphocyte group and lymphocytes with high concentration of 5-FU group （Pgt;0.05）. The IOD of CD8+ expression in lobules of liver was not different among all the three lymphocytes treated groups （Pgt;0.05）. But in portal areas, CD8+ expression was lower in the lymphocytes with low concentration of 5-FU group than in the other groups （Plt;0.05）. ConclusionPreinfusion of lymphocytes treated with low concentration 5-FU can induce graft immune tolerance, the probable mecanism of which is the increasing Fas-L expression in graft.
Objective To study the relation between changes of the hepatic energy metabolism and allograft viability in early phase after orthotopic liver transplantation, arterial blood ketone body ratio (AKBR) was measured in pre- intra and post-operative phase. Methods The monkeys were divided into two groups in accordance with survived times. A group (＞24h), 5 monkeys survived 29—168 postoperative hours; B group (＜24h), 9 monkeys survived only 5—22 hours. Results AKBR in all models immediately decreased to extraordinarily low state in anhepatic-phase (versus preanhepatic phase, Ｐ＜0.01), and A group recovered rapidly to the normal levels, and maintained continuously for 12 postoperative hours above the level of 0.7. In contrast in B group, AKBR decreased below 0.7 rapidly and failed to restore to the normal level. Within 12 hours postoperatively, in B group, AKBR was lower than 0.4. Conclusion AKBR is a sensitve indicator to the allograft viability in the early phase after hepatic transplantation.