Effects of Kupffer cell inactivation on graft survival and liver regeneration after partial liver transplantation in rats

BACKGROUND： Gadolinium chloride（Gd Cl3） selectively inactivates Kupffer cells and protects against ischemia/reperfusion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplantation（PLTx） is not clear. This study was to investigate the role of Gd Cl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process.METHODS： PLTx（30% partial liver transplantation） was performed using Kamada’s cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose（5 mg/kg） and high-dose（10 mg/kg） Gd Cl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regeneration by PCNA staining and Brd U uptake, apoptosis by TUNEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting.RESULTS： Gd Cl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine aminotransferase and aspartate aminotransferase（P〉0.05）. Gd Cl3 pretreatment induced apoptosis and inhibited IL-6 overexpression and STAT3 phosphorylation after PLTx in graft tissues.CONCLUSION： Kupffer cells may contribute to the liver regeneration after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.

Partial liver transplantation

Partial liver transplantation,including reducedsize liver transplantation,split liver transplantation,and living donor liver transplantation,has been developed with several innovative techniques because of donor shortage.Reduced-size liver transplantation is based on Couinaud’s anatomical classification,benefiting children and small adult recipients but failing to relieve the overall donor shortage.Split liver transplantation provides chances to two or even more recipients when only one liver graft is available.The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situ to ensure long-term quality.The first and most important issue involving living donor liver transplantation is donor safety.Before surgery,a series of donor evaluations—including anatomical,liver volume,and liver function evaluations—is indispensable,followed by ethnic agreement.At different recipient conditions,auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation,which employ piggyback techniques,are good alternatives.Partial liver transplantation enriches the practice and knowledge of the transplant society.

Establishment of a new pig model for auxiliary partial orthotopic liver transplantation

AIM: To establish a new pig model for auxiliary partial orthotopic liver transplantation (APOLT).METHODS: The liver of the donor was removed from its body. The left lobe of the liver was resected in vivo and the right lobe was used as a graft. After the left lateral lobe of the recipient was resected, end-to-side anastomoses of suprahepatic inferior vena cava and portal vein were performed between the donor and recipient livers,respectively. End-to-end anastomoses were made between hepatic artery of graft and splenic artery of the host.Outside drainage was placed in donor common bile duct.RESULTS: Models of APOLT were established in 5 pigs with a success rate of 80%. Color ultrasound examination showed an increase of blood flow of graft on 5th d compared to the first day after operation. When animals were killed on the 5th d after operation, thrombosis of hepatic vein (HV) and portal vein (PV) were not found. Histopathological examination of liver samples revealed evidence of damage with mild steatosis and sporadic necrotic hepatocytes and focal hepatic lobules structure disorganized in graft. Infiltration of inflammatory cells was mild in portal or central vein area. Hematologic laboratory values and blood chemical findings revealed that compared with group A (before transplantation), mean arterial pressure (MAP), central venous pressure (CVP), buffer base (BB), standard bicarbonate (SB) and K+ in group B (after portal vein was clamped) decreased (P＜0.01). After reperfusion of the graft, MAP, CVP and K+ restored gradually.CONCLUSION: Significant decrease of congestion in portal vein and shortened blocking time were obtained because of the application of in vitro veno-venous bypass during complete vascular clamping. This new procedure,with such advantages as simple vessel processing, quality anastomosis, less postoperative hemorrhage and higher success rate, effectively prevents ischemia reperfusion injury of the host liver and deserves to be spread.

Hepatofugal Portal Flow Associated with Acute Rejection in Living-donor Auxiliary Partial Orthotopic Liver Transplantation:A Report of One Case and Literature Review

We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study.On postoperative day 6,continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein.Based on histological findings,acute rejection was the suspected cause.The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies.The patient was discharged on the 30th postoperative day.It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection,and can be successfully treated by anti-rejection therapy.

Early graft dysfunction following adult-to-adult livingrelated liver transplantation:Predictive factors and outcomes

AIM:To describe a condition that we define as early graft dysfunction(EGD)which can be identified preoperatively. METHODS:Small-for-size graft dysfunction following living-related liver transplantation(LRLT)is characterized by EGD when the graft-to-recipient body weight ratio(GRBWR)is below 0.8%.However, patients transplanted with GRBWR above 0.8%can develop dysfunction of the graft.In 73 recipients of LRLT(GRBWR>0.8%),we identified 10 patients who developed EGD.The main measures of outcomes analyzed were overall mortality,number of re-transplants and length of stay in days(LOS).Furthermore we analyzed other clinical pre-transplant variables,intraoperative parameters and post transplant data.RESULTS:A trend in favor of the non-EGD group(3-mo actuarial survival 98%vs 88%,P=0.09;3-mo graft mortality 4.7%vs 20%,P=0.07)was observed as well as shorter LOS(13 d vs 41.5 d;P=0.001)and smaller requirement of peri-operative Units of Plasma (4 vs 14;P=0.036).Univariate analysis of pre- transplant variables identified platelet count,serum bilirubin,INR and Meld-Na score as predictors of EGD. In the multivariate analysis transplant Meld-Na score (P=0.025,OR:1.175)and pretransplant platelet count(P=0.043,OR:0.956)were independently associated with EGD. CONCLUSION:EGD can be identified preoperatively and is associated with increased morbidity after LRLT. A prompt recognition of EGD can trigger a timely treatment.