Objective To explore the application strategies of immunosuppression scheme after different types of liver transplantation for liver diseases. Methods According to the published literatures and the practical experiences in organ transplant center of Tianjin First Center Hospital,the immunosuppression schemes used after liver transplantation,the liver transplantation in patients with hepatitis C or liver cancer,patients after liver re-transplantation or with concurrent infection or with renal injury were summarized,and the spontaneous controllable tolerance (SOT) and the dosage reduction or elimination of immunosuppressor were approached. Results① Dose reduction and combined drugs therapy were the important strategies to adjust immunosuppressor after liver transplantation.②Maintaining low level immunosuppression,avoiding the repeat of cell rejection reaction and actively implementing antiviral therapy could slow down the progress of fibrosis after liver transplantation in HCV patients with recurrent hepatitis.③The induction therapy using anti CD25 monoclonal antibody and based on sirolimus(SRL) maintaining immune inhibition were the related factors to improve the survival rate of liver transplantation in patients with liver cancer. ④ We needed to strengthen the immune inhibitor concentration detection and timely adjust the dosage of calcineurin inhibitors(CNIs)or SRL after liver re-transplantation or when there was infectious complication. In severe cases with infection,we could consider to remove them.⑤We could reduce the progression of renal injury after transplantation by decreasing the CNIs or converting to SRL.⑥Inducing stable and durable immune tolerance and designedly withdrawing the immunosuppressor after liver transplantation in relatively stable patients,we might expect 20% patients achieving SOT. Conclusions The progress of immunosuppression scheme after liver transplantation on the one hand depends on the successive development of new types of immunosuppressor with lower adverse effect, and on the other hand,the more accurate genomics,pharmacogenetics and pharmacokinetic methods for monitoring the transplanted liver damage are necessary. We also need to look for specific immune monitoring methods to accurately assess the effectiveness and toxicity of immunosuppressive agents to gradually withdraw or stop the immunity inhibitors.

ObjectiveTo summarize 20 ABO-incompatible liver transplantation cases in our hospital and explore the treatment strategy. MethodsFrom January 2009 to July 2011,20 cases donorrecipient ABO blood type not-identical liver transplantation was performed at our hospital. 16 cases were ABO-incompatible(ABO-Ⅰ) and 4 were ABO-compatible(ABO-C ).The median follow-up was (13.3 ± 9.2) months.ResultsExcept preoperative MELD score,there were no significant difference in other perioperative data,the incidence of postoperative complications and the cumulative survival rate between ABO-C and ABO-Ⅰ group.There were 5 deaths in 20 cases,2 cases in ABO-C group and 3 cases in ABO-Ⅰ group,survival rate was 75％.The cause of death was perioperative multiple organ failure in 2 cases,liver cancer recurrence in 2 cases and cerebral hemorrhage in 1 case.There were 2 cases of acute rejection,3 cases of biliary complications and 3 cases of portal vein thrombosis developing postoperatively. Eleven patients had increased serum creatinine after operation,preoperative high creatinine existed in 6 cases and it maintained posttransplant high level for more than 7 days,the serum creatinine level in other 7 patients was back to normal level in 7 days.ConclusionsA combination splenectomy before the portal vein reperfusion,the protocol of basiliximab,tacrolimus (TAC)/mycophenolate mofetil (MMF)/steroids immunosuppression treatment,postoperative peripheral vascular dilatation treatment by Alprostadil,help achieve favorable outcome in selected patients who underwent ABO-incompatible liver transplant.

Objective To study the prognosis of patients with end-stage liver cirrhosis who using controlled cardiac death liver donor in situ liver transplantation. Methods Seven cases of transplants which used liver donated after cardiac death were done in our center. The preoperative and postoperative data were analyzed. The prognosis of these patients was observed. Results Except one recipient died of upper gastrointestinal bleeding at the 9th day after surgery, the remaining 6 patients were followed up for more than 12 months (mean 15.7 months) and the prognosis was satisfactory.Conclusion Patients can get good prognosis after the liver transplants with donated liver after cardiac death which meets the Maastricht Classification type Ⅲ.

Objective To analyze the curative effects and survival results of combined liver kidney transplantation (CLKT).Methods From 2002 to 2011,the clinical data of 36 Chinese patients who underwent CLKT were retrospectively analyzed in our centre.The age of recipients was 47.4 ±13.1 years.Four patients had undergone liver transplantation and 7 patients kidney transplantations before CLKT, respectively. The complications and the survival were analyzed. Results The survival patients were followed up for 47.9 months (29.1 - 115.7).The cumulative 1-,3 and 5-year patient survival rate was 88.7％,85.4％ and 81.4％; The 1,3- and 5-year survival rate of liver graft was 79.8％,76.3％ and 72.3％; The 1-,3- and 5 year survival rate of kidney graft was 85.7％,82.4％ and 78.2％.Three patients underwent liver re-transplantation due to severe biliary complications,and one patient kidney re-transplantation due to renal allograft dysfunction.Conclusion CLKT is a effective treatment for end-stage liver disease with renal insufficiency and achieves excellent results.

ObjectiveTo summary clinical character of de novo hepatitis B virus infection after liver transplantation,and explore the strategy of prevention and treatment.MethodsThe clinical data of recipients undergoing liver transplantation and the recipients who developed de novo hepatitis B virus infection after liver transplantation between Jan. 2000 to Dec. 2010 were retrospectively analyzed.Results365 patients who underwent liver transplantation were negative for serum HBsAg before liver transplantation.Among them,11patients were diagnosed as having de novo hepatitis B virus infection after liver transplantation,with the morbidity being 3.0 ％(11/365).Most recipients did not have any clinical presentation.They were just found HBsAg positive during the follow-up period.The liver functions were normal.All 11patients received anti-virus therapy after they were found having positive HBsAg and replicated HBV-DNA.One patient whose primary disease was hepatitis C combined with primary hepatic carcinoma was treated with pegylated interferon,thereafter,he was found having YMDD-mutation of HBV-DNA,and he was treated with entecavir.The rest 10 patients received anti-virus treatment with nucleoside analog.The 10 recipients were injected with hepatitis B immunoglobin during operation.After anti-HBV therapy,one patient died from acute liver failure because of inefficient treatment,and one patient died from tumor recurrence.The remaining nine patients survived:HBeAg of one patient became negative,and HBV-DNA replications of the four patients became negative (＜1×105 copies/L).The liver function of the patients who survived was normal.ConclusionFor recipients who were HBsAg negative before liver transplantation,when they received liver transplantation,,they should be given strict screening of blood product for transfusion.The liver transplantation patient who is HBsAg negative in serum before liver transplantation,and whose donor is HBcAb positive in serum and/or HBV-DNA positive in serum,should be treated with HBIG and/or nucleoside analog during operation or after operation,as we said above is a ideal strategy to prevent de novo hepatitis B virus infection after liver transplantation.The prognosis of de novo hepatitis B virus infection after liver transplantation is mild.

ObjectiveTo study the role of middle hepatic vein (MHV) on the early function and regeneration of the donor remnant liver in living donor liver transplantation (LDLT).Methods Between August 2007 and August 2008,66 LDLT were performed,36 without MHV (group A),and 30 with MHV (group B) in the donor liver.The donor operation time,intraoperative blood loss,postoperative hospital stay,serum bilirubin,international normalized ratio (INR),alanine aminotransferase (ALT) and albumin were analyzed.We measured the volume of remnant liver with CT scan at 2 weeks after operation,and compared the function and regeneration of the remnant liver between the two groups. Results At 2 weeks after operation,there was no significant difference (P=0.16) in the volume of remnant liver between group A (959.3±195.2 ml) and group B (883.7±155.5 ml).There was also no difference (P=0.62) in the regeneration rate of segment IV between group A (78.2 ％ ± 29.1 ％) and group B (82.7 ％ ± 40.4％).The serum bilirubin,INR and ALT in group B was significantly higher than group A immediately after liver transplantation,but there was no difference at 1 week after transplantation.ConclusionExtended right hepatectomy with MHV was safe,and did not significantly impact early liver function and regeneration in the donor.

Objective Small-for-size syndrome (SFSS) is a common and serious problem after living donor liver transplantation (LDLT) of small grafts.To prevent SFSS by selecting large enough graft,enlarging outflow tract,and controlling the portal vein pressure and flow during LDLT.Methods 113 adult LDLT recipients were reviewed from Dec.1,2007 to Nov.30,2009.Enlarging the portal outflow tract by the incision of the anterior rim of the orifice of the right hepatic vein (RHV),modificating graft inflow,and selecting large enough graft were done to prevent SFSS.The relationship between the patients' GRWR,portal vein flow,portal vein pressure and the occurrence of SFSS was analyzed.Results All patients received the outflow orifice modification.The portal vein pressure and the portal vein flow were decreased after spleen artery ligation.No SFSS ocurred.Conclusion Selecting large enough liver graft,and enlarging portal vein inflow and outflow were safe for the LDLT recipients,and can effectively prevent SFSS.

Objective To investigate the clinicopathological characteristics of retransplantation for intrahepatic recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT).Methods In a center hospital of organ transplantation setting,9 patients after primary liver transplantation had intrahepatic recurrence and received retransplantation,and 12 patients in control group were not subjected to LT over the same period.The follow-up period was 10 to 58 months.Results As compared the pathological characteristics of secondary transplanted liver with primary thansplanted liver,there was significant difference in tumor differentiation (grade Ⅱ,Ⅲ and Ⅳ)between primary group (33％,67％ and 0) and secondary group (22％,22％ and 56％) (P＜0.01).After primary liver transplantation,median of tumor free survival was 15.0 months.After secondary liver transplantation,median of survival was 5.8 months,and median of tumor free survival was 2.5 months.In control group,median of tumor free survival was 13.0 months,and total survival survival was 17.6 months.In transplantation group and control group,1-,2-,and 3-year cumulative survival rate was 89％,44％,33％ and 91％,45％,9％ respectively,with the difference being not statistically significant (P ＞ 0.05).Conclusion It is high risk of vascular invasion for tumor recurrence.The differentiation grade of recurrent tumor is lower.The sign of intrahepatic recurrence of HCC after liver transplantation may be early and local clinical characteristics of tumor cell disseminating and metastasis before and during operation,and it is not recommended to perform retransplantation.

Objective To assess the clinical application of Cylex ImmuKnow assay in patients with renal dysfunction after liver transplantation for individualized immunosuppressive therapy.Method Twenty adult patients undergoing liver transplant between January 2009 and December 2011 received regular ImmuKnow assay monitoring combined with determination of serum tacrolimus trough concentration to guide immunosuppressive regimens,all of whom showed sustained renal dysfunction 6 months after transplant with normal and stable liver function.Clinical data were collected to observe the changes of renal function in those patients after treatment.Results The recipients were followedup for 15-54 months,received ImmuKnow assay 61 times and the results fluctuated 33-943 μg/L [median 282 μg/L,interquartile range (IQR) 267 μg/L].After ImmuKnow monitoring,serum creatinine level in patients was decreased significantly from median 151.8 μmol/L with IQR 44.9 μmol/L to median 114.9 μmol/L with IQR 35.3 μmol/L (Z =-3.845,P =0.000),and estimated glomerular filtration rate (eGFR) was increased significantly from median 0.746 mL/s with IQR 0.025 mL/s to median 1.005 mL/s with IQR 0.454 mL/s (Z =-3.771,P =0.000).ImmuKnow results showed a linear correlation with the white blood cell count in patients (Spearman correlation coefficient r =0.429,P =0.001),but no linear correlation with the patients' age,primary disease before transplantation,postoperative time,serum tacrolimus trough concentration,lymphocyte count,CD3+ T lymphocyte count,CD4+ T lymphocyte count or CD4+/CD8+ T lymphocyte ratio (P＞ 0.05).Conclusion Cylex IrmmuKnow assay can be applied in patients with renal dysfunction after liver transplantation for individualized immunosuppressive therapy monitoring,which is of certain clinical value.

Objective To identify the changes of anti-HBs titers of patients with hepatitis B virus (HBV)-related diseases in the early stage (within the first week) post-liver transplantation (LT) and analyze their influencing factors.Method A total of 26 patients were enrolled in this study.They were all positive for HBsAg pre-LT and received the prophylaxis of lamivudine in combination with intravenous hepatitis B immunoglobulin (HBIG) in the first week post-LT.The titers of anti-HBs were detected daily in blood and drainage fluid every day in the first week post-LT.If the anti-HBs titers were greater than 1000 IU/L,blood and drainage were diluted,then detected again.Result The titers of anti-HBs in HBV-DNA negative groups,low HBsAg groups,and HBeAg negative groups were higher than those in the HBV-DNA positive groups,high HBsAg groups and HBeAg positive groups in the first five days post-LT.The median titer of anti-HBs in drainage fluid was 181.60 IU/L (0.00-968.50 IU/L).And the titer of anti-HBs in drainage fluid was correlated with anti-HBs titers in blood at the same time (r =0.927,P =0.000).The amount of anit-HBs calculated in drainage fluid was very high,but it fluctuated in a wide range (0.00-908.55 IU).Conclusion In the early stage post-LT,patients in high risk groups should receive higher doses of HBIG to maintain safe levels of anti-HBs,while the lower doses of HBIG are enough to the patients in low risk groups.Furthermore,the anti-HBs titers in blood aren't affected by the anti-HBs loss in drainage fluid.