Objective To establish different kinds of reduced size liver transplantation model of rats， and to explorethe optimal marginal size of liver graft in orthotopic liver transplantation， in purpose of providing a kind of animal modelfor the study about mechanism and prevention measures of small-for-size syndrome. Methods One hundred and ninety-two rats were randomly divided into whole liver graft transplantation group （underwent whole liver graft transplantation），half liver graft transplantation group （the median lobe and right lobe of the liver were selected to be the graft）， small size liver graft transplantation group （the median lobe of the liver was selected to be the graft）， and extra-small size liver graft transplantation group （the median lobe and left lobe of the liver were reduced， and remained lobes were selected to be the graft）， each group enrolled 48 rats. After liver graft transplantation， 24 rats of each group were selected to observe the survival situation， 12 rats of each group were selected to measure portal venous pressure at time point of before operation，and 5， 15， 30， 45， and 60 minutes after transplantation. The other 12 rats of each group were test the level of alanine aminotransferase （ALT）. Results Seven-day survival rate of the whole liver graft transplantation group， half liver graft transplantation group， small size liver graft transplantation group， and extra-small size liver graft transplantation group was 100% （24/24）， 87.5% （21/24）， 37.5% （9/24）， and 0 respectively. Portal venous pressure of whole liver graft trans-plantation group was stable after opening the portal vein， although there was slight increase at prophase in half liver graft transplantation group， and then the portal venous pressure would let down， keeping stable at the later stage. But in small size liver graft transplantation group and extra-small size liver graft transplantation group， the portal venous pressure incr-eased and got the top at 15 minutes after opening the portal vein， and then induced， keeping stable during the 45-60 minutes.Portal venous pressure at the point of 5 （r=-0.942）， 15 （r=-0.947）， 30 （r=-0.900）， 45 （r=-0.825）， and 60 （r=-0.705）minutes after opening the portal vein were significantly related to liver graft size （P＜0.001）. The levels of ALT in wholeliver graft transplantation group and half liver graft transplantation group were both lower than those of small size livergraft transplantation group and extra-small size liver graft transplantation group （P＜0.05）， and levels of ALT in small size liver graft transplantation group was lower than extra-small size liver graft transplantation group too （P＜0.05）. Levelof ALT at 24 hours after transplantation were significantly related to liver graft size （r=-0.685， P＜0.001）. Conclusions The minimum graft volume/standard liver volume （GV/SLV） in reduced size liver transplantation in rat is 50%. The liver graft whose GV/SLV is 30%-35% should be considered as marginal size liver graft， and the liver graft whose GV/SLV less than 30% should be considered as extra-small size liver graft in the rat.
Objective To approach the prognosis after liver transplantation （LT） of liver function for Child grade A in patients with portal hypertension， and to compare with periesophagogastric devascularization with splenectomy （PDS）. Methods The data of 195 portal hypertension cases with Child A caused by hepatitis B cirrhosis who received surgical treatment of PDS （152 cases） or LT （43 cases） in division of liver transplantation center of West China Hospital of Sichuan University from 1999 to 2011 were retrospectively analyzed. The pre-， intra-， and postoperative variables in two groups that including patients’ age， score of Child， score of model for end-stage liver disease （MELD）， total bilirubin （TB），creatinine （Cr）， international normalized ratio （INR）， albumin （Alb）， complications of portal hypertension， amount of intraoperative bleeding and blood transfusion， operative time， and in the ICU and hospital stay time were compared. The postoperative outcomes were statistically analyzed including severe postoperative complications， short-term and long-term survival rates. Results Compared with PDS group， the amount of intraoperative bleeding and blood transfusion of LT group were morer （P＜0.05）， the operative time， in the ICU and hospital stay time of LT group were longer （P＜0.05）. The rate of severe postoperative complications in LT group was higher than that in PDS group 〔18.60% （8/43） vs. 1.97% （3/152），P＜0.05〕. The levels of TB and Cr during the postoperative period in LT group were higher than that in PDS group （P＜0.05）. Although the INR on day 1 after operation in LT group was higher than that in PDS group （P＜0.01）， but the difference disappeared soon on day 7 after operation in two groups （P＞0.05）.The 1-， 3-， and 5-year survival rates of the LT and PDS groups were 90.3%， 86.5%， 86.5%， and 100%， 100%， 100%， respectively， significant difference were observed in both short-term and long-term survival rates between the two groups （P＜0.05）. Conclusion LT offered no significant survival benefit to patients with portal hypertension and Child A due to hepatitis B cirrhosis， whereas PDS could be an effective treatment.
Objective To explore the feasibility and safety of liver transplantation （LT） in treatment of upper gastrointestinal hemorrhage in patients with portal hypertension， and to compare the therapeutic effects with conventional operation （CO）. Methods The clinical data of 303 patients with bleeding portal hypertension from Feb. 2009 to Feb. 2012 in the department of hepatobiliary and pancreatic surgery of First Affiliated Hospital of Zhejiang University were retrospectively analyzed. One hundred and one patients received LT procedure （LT group）， whereas the other 202 patients received CO procedure （CO group）. Postoperative follow-up period was 8-44 months （average 26 months）. Results Liver function before operation in CO group was significantly better than that in LT group（P＜0.01）. The mortality of CO group and LT group were 7.4%（14/189） and 3.0%（3/101， P=1.00）， respectively. The rebleeding rate of patients underwent LT was 2.0%（2/101）， significantly lower than that of CO group 〔9.5%（18/189）， P＜0.05〕. The vanish rate of esophagogastric varice in patients underwent LT was 86.1%（87/101）， significantly lower than that of CO group 〔54.5%（86/189）， P＜0.01〕. Conclusions LT treatment for bleeding portal hypertension is feasible and safe. Patients with good liver function despite hemorrhage history may be managed satisfactorily with conventional surgery. LT is the only curative treatment for patients with portal hypertension in end-stage liver disease.
ObjectiveTo determine the risk factors for recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). MethodsThe clinical data from seventysix consecutive HCC patients who underwent OLT were retrospectively analyzed. The patients were divided into nonrecurrence group (n=53) and recurrence group (n=23) based on recurrence, and the characteristics of tumor recurrence were analyzed. ResultsThe overall recurrence rate of tumor was 30.3% (23/76). By univariate analysis, gender (P=0.449), age (P=0.091), received preoperative therapy or not (P=0.958), tumor numbers (P=0.212), and HBV/HCV infection (P=0.220) were not closely related with tumor recurrence, while the integrality of tumor capsule (P=0.009), tumor stage (P=0.002), tumor diameter (Plt;0.001), vascular invasion (Plt;0.001), and AFP level before transplantation (P=0.044) were significantly related with tumor recurrence. Furthermore, the oneyear recurrence rate of tumor was higher in patients whose AFP level returned to normal within two months after transplantation (Plt;0.001) and tumor diameter was less than 5.0 cm (P=0.001). Multivariate analysis revealed that tumor diameter (P=0.001, OR=6.456, 95%CI: 2.356-17.680), vascular invasion (P=0.030, OR=10.653, 95%CI: 1.248-90.910), and AFP level before transplantation (P=0.017, OR=2.601, 95%CI: 2.196-5.658) were independent risk factors for tumor recurrence. ConclusionMore attentions shall be paid to these patients with tumor diameter gt;5.0 cm, vascular invasion, and AFP level before transplantation ≥400 μg/L, in particular AFP level is beyond normal within two months after transplantation, and antitumor therapy shall be given as soon as possible.
Objective To study the mechanism of immune hyporesponsiveness of allograft rejection induced by transfusion nonpufsed allopeptide syngeneic immature dendritic cell (imDC) generated from recipient bone marrow progenitors and to explore a possible strategy for liver allograft protection in clinic. Methods Forty experimental rats were randomly divided into 4 group: control group, cyclosporine A (CsA) group, mature DC (mDC) group and imDC group. In control group, Wistar rats only received liver transplantation. In CsA group, Wistar rats underwent liver transplantation plus CsA treatment 〔10 mg/（kg·d)〕. In mDC group, recipient-derived mDC 1×106 were infused intravenously through the penile vein to Wistar rats. In imDC group, ImDC with the dose of 1×106 were injected into Wistar rats via the dorsum vein of penile. In each group, five recipients were killed on the 10th day after transplantation, the other five recipients were left to observe survival time. The levels of ALT, AST, TBIL, IL-2, IFN-γ, IL-4 and IL-10 were detected. The acute rejection and the expression of FasL/Fas in the grafts were detected by HE and immunohistochemical staining. Western blot was used to detect Scurfin protein expression of CD4+ CD25+ T cells. Results The median survival time of the liver allografts in CsA group and imDC group were significantly longer than that in control group and mDC group ( P ＜ 0.05). The levels of ALT and TBIL in control group and mDC group were significantly higher than those in CsA group and imDC group ( P ＜ 0.05). Compared with CsA group and imDC group, the levels of IL-2 and IFN-γ were higher but the levels of IL-4 and IL-10 were lower in control group and mDC group ( P ＜ 0.01). Slightly or no rejection reaction was found in CsA group and imDC group ( P ＜ 0.05). The Scurfin protein expressions of CD4+ CD25+ T cells of imDC group were significantly higher than those of other three groups. Conclusion Application of nonpufsed allopeptide syngeneic recipient-derived imDC is an effective way to induce immune hyporesponsiveness by blocking indirect recognition in rat liver transplantation model. Survival span is significantly prolonged by its protective effect. The mechanism of immune hyporesponsiveness induced by imDC transfusion might be involved in some aspects: T cell apoptosis, immune deviation of Thl/Th2 cytokine net and inhibition of T lymphocytes responsiveness by regulatory T cells.
Objective To investigate the clinical significance of intra-abdominal pressure measure in patients with liver transplantation by summarizing the data of 143 cases. Methods Intra-abdominal pressure was indirectly measured by urinary bladder pressure. Intra-abdominal pressure over 10 cm H2O (1 cm H2O=0.098 kPa) was regarded as intra-abdominal hypertension (IAH), and 10＜pressure≤15 cm H2O as gradeⅠ, 15＜pressure≤25 cm H2O as grade Ⅱ, 25＜pressure≤35 cm H2O as grade Ⅲ, over 35 cm H2O as grade Ⅳ. The parameters of circulatory system, respiratory system, renal function and the postoperative intra-abdominal pressure for 7 days were recorded to every patient, and the parameters of each grade IAH group were contrasted with non-IAH group. ResultsAmong 143 cases, 45 cases were IAH (31.5%), in which 18 cases belonged to grade Ⅰ, 13 cases belonged to grade Ⅱ, 11 cases belonged to grade Ⅲ, while 3 cases belonged to grade Ⅳ. Compared with those in non-IAH group, SCr and BUN significantly increased (P＜0.05, P＜0.01), PaO2 significantly decreased (P＜0.05, P＜0.01) in each grade IAH group; Respiratory frequency (RF), heart rate (HR) and PaCO2 significantly increased (P＜0.05, P＜0.01) in some grade IAH group (HR in grade Ⅱ, Ⅲ and Ⅳ, RF and PaCO2 in grade Ⅲ and Ⅳ). Conclusions Intra-abdominal hypertension would affect liver function by impaired circulatory, respiratory and renal function. So, it is necessary to measure intra-abdominal pressure for patients after liver transplantation, which can help to choose appropriate treatment.
Objective To explore the effect of cytotoxic T lymphocyte-associated antigen 4 (CTLA4-Ig) fusion protein on the function of orthotopic liver allograft. Methods Orthotopic liver allograft models of rhesus monkeys were established in this study. The survival time, liver function and morphologic changes of graft were observed, respectively. The levels of IL-2 and IL-10 were detected by ELISA. Apoptosis was monitored by TUNEL.Results The average survival of control group was 6.57 d, while the average survival of CTLA4-Ig group was 14.92 d, which was statistically prolonged (Plt;0.05). Serum ALT level was highly increased, and Alb level decreased obviously in control group. While the levels of ALT and Alb kept in normal in CTLA4-Ig group. After day 3-7, the expressions of IL-2 were highly expressed in control group, while the expressions of IL-10 in CTLA4-Ig group were higher than those of control group. The severity of rejection reaction after day 3 was weaker in CTLA4-Ig group than that of control group by histological assessment. The apoptosis index after day 3 in the liver cells was highly increased in control group as compared with the CTLA4-Ig group. Conclusions CTLA4-Ig fusion protein therapy can induce immunotolerance and prolong the survival of recipients. The increasing of cytokines IL-2 or the decreasing of cytokines IL-10 may be one of the laboratory indexes in monitoring immunotolerance of transplantation.
Objective To investigate the prevention of HBV reinfection in the perioperative period of liver transplantation on HBV-related diseases． Methods Published papers were collected and reviewed． Results HBV-related diseases were the main indications of liver transplantation．The prevention for HBV reinfection affects the survivals remarkably. Nowadays, a lot of medication have been used in the prevention of HBV reinfection， and the therapeutic regimens were different from each other. Conclusion Liver transplantation is an effective treatment for HBV-related disease． Appropriate prevention of HBV reinfection in the perioperative period of liver transplantation is important for the survivals of patients．
【Abstract】Objective This study was conducted to build experimental model of orthotopic liver transplantation in rat (ROLT) with the character of acute rejection; and to study the effect of cytotoxic T lymphocyte antigen 4 immunoglobulin G (CTLA4Ig) on prevention of rejection and the induction of immune tolerance of ROLT. Methods Build model of Wistar→SD ROLT(performed by the two cuff method) with character of acute rejection.Recipients were injected with CTLA4Ig 75 μg per ROLT into abdominal cavity after 2 days of operation. Contrast was made with no treatment group, the clinical characters, the liver function, the transplantated liver pathologic character and the concentrations of TNFα in serum were observed and measured on postoperative day 7. In treatment group, all above observation were done on postoperative month 4. Above all, determination of the effect of CTLA4Ig on preventing acute rejection and inducing tolerance in ROLT was observed.Results ①Recipients (no treatment group) died one by one within 6th～14th days; pathologic character of rejection in transplantation liver could be found; ② In treatment group, on postoperative day 7 and month 4, no clinical rejection character and no pathologic character of rejection in transplantation liver were found and serum concentration of cytokins related to TNFα found lower than that of contrast group(P＜0.05), and serum concentration of ALT、AST、TBIL、DBIL found lower too(P＜0.05); But serum concentration of TP and Alb was found higher than that of contrast group(P＜0.05). Conclusion ① CTLA4Ig treatment alone inhibits the rejection responce in ROLT. ② CTLA4Ig treatment can Prevent rejection and induce immune tolerance in ROLT model with characters of acute rejection; the serum concentration of cytokins related to TNFα can probably be used as evaluation standard of rejection in ROLT rejection.
【Abstract】Objective To introduce the birth and development of model of endstage liver disease (MELD) and evaluate its effect on liver transplantation(LT) as a new scoring system. Methods Literatures of MELD applied in LT were analyzed retrospectively. Results MELD scoring system was used for predicting the prognosis of patients with endstage liver disease and the death risk of candidates on waiting LT extensively and the order of organ sharing was determined by its predicable results. Conclusion MELD has been had a successful initial implementation for predicting the shortterm survival probability and mortality in patients with endstage liver disease, and meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, which has been proven to be a powerful tool for auditing the liver allocation system.