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.

Objective To explore the efficacy of liver retransplantation for hepatocellular carcinoma (HCC) patients with or without HCC recurrence.Method 131 cases of retransplantation performed between 2003 and 2012 were analyzed retrospectively.Their first and second liver transplantations were both performed in our hospital.Diagnoses of their primary diseases before transplantations were confirmed pathologically after the first transplantation.Patients were divided into two groups in terms of benign causes and HCC.Results Sixty cases were fallen into benign disease group and 65 cases into HCC group.The proportions of main causes of retransplantation were similar between two groups.The graft survival rate of early retransplantation (retransplantation performed within 30 days after the first transplantation) and late retransplantation (retransplantation performed beyond 30 days after the first transplantation) was calculated and compared respectively due a great difference in survival rate between the two phrases.The deaths of HCC patients with HCC recurrence before retransplantation were more than those without HCC recurrence (P＜0.01) and benign disease group.The 5-year cumulated survival rate was close between HCC patients without recurrence before retransplantation (51.0％) and benign disease group (51.8％).Conclusion The retransplantation after HCC recurrence has an unacceptable prognosis.The survival rate was similar between patients without HCC recurrence and patients with benign diseases.HCC patients without recurrence should not be restrained from retransplantation just for the HCC history.

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 establish and evaluate the animal model induced by inhalation injury of airborne fine particulate matter (PM2?5). Methods We manufactured equipment for rats aerosol inhalation with PM2?5. The effects of several facters such as concentrations(100 ± 10 μg/m3、150 ± 10 μg/m3、200 ± 10 μg/m3 )、time(1w、2w、4w、8w、12w)、method (non?exposed intratracheal instillation method and aerosol inhalation) and animals (Wistar rats, BN rats and guinea pigs) were investigated to establish the model. The respiratory rate, forced vital capacity ratio of forced expiratory volume ( FEV1/FVC) and arterial partial pressure of oxygen ( PO2 ) were measured, the pathological changes of bronchial and lung tissues under light microscope were observed. The success animal model was builded as the pneumonia was observed from the pathological changes of lung tissue. Results The Wistar rats exposed to PM2?5 aerosol inhalation for 8 weeks, we can see that the weight growth rate of rat decreased, WBC count and mononuclear cells count increased, the macrophages ratio decreased in BALF, the respiratory rate of lung increased while arterial PO2 and FEV1/FVC decreased, inflammation and pulmonary fibrosis changes were observed by bronch and pulmonary pathology, inflammatory changes with a dose?response relationship were observed. Exposed to PM2?5 aerosol inhalation for different time(1 w、2 w、4 w、8 w、12 w)with same dose, the score issue lesions of lung and bronchus in Wistar rats increased and the 8w group is obvious. The Wistar rats exposed to PM2?5 with different method ( aerosol inhalation and non?exposed intratracheal instillation method) for 8w, the aerosol inhalation worked as effectively as perfusion while mortality rate of aerosol inhalation is lower. Different animals ( Wistar rats, BN rats and guinea pigs) exposed to PM2?5 aerosol inhalation for 8w, the same results were observed with three method respectively while mortality rate of Wistar rats lower. Conclusions The optional conditions that the Wistar rats were continuously inhaled for 8w PM2?5 with a dose of 150 ± 10 μg/m3 were established. The animal model could be used on a national scale, especially in Fujian province. The results would be useful for the development of the research of the prevention and countermeasures of PM2?5 pollution.

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.

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 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 investigate the prognosis of liver retransplantation in patients with transplanted liver function failure caused by viral hepatitis recurrence.Methods From January 20th 2003 to November 20th 2012,the clinical data of 215 patients with liver retransplantation were retrospectively analyzed.The survival of transplanted liver of 18 cases with liver retransplantation because of hepatitis recurrence (eight cases of hepatitis C and 10 cases of hepatitis B) was compared with that of 115 cases with liver retransplantation for biliary complications.The dysfunction of transplanted liver after first transplantation and the survival after second liver retransplantation of patients with hepatitis C recurrence were compared with those of patients with hepatitis B recurrence.The prognosis analysis was compared by survival curves made by Kaplan-Meier method.Results Biliary complications were the most common reason in 215 patients with second liver retransplantation and which accounted for 115 cases (53.5 ％).Eighteen cases were hepatitis recurrence (8.4 ％).There was no significant difference in survival rate of the second transplanted liver between patients with hepatitis recurrence and biliary complication (P =0.543).The dysfunction of transplanted liver occurred at early stage (in three months) after first liver transplantation in part of patients with hepatitis C recurrence.The dysfunction of transplanted liver almost all occurred two years after first liver transplantation in patients with hepatitis B recurrence.Among eight patients with hepatitis C recurrence,the second transplanted liver of five cases survived more than one year.All the second transplanted liver of 10 patients with hepatitis B recurrence survived more than one year.There was no significant difference between them (P =0.060).Conclusions The prognosis of liver retransplantation in patients with hepatitis recurrence is similar with that of patients with biliary complications.The prognosis of liver retransplantation in patients with hepatitis B recurrence is good.

Objective To evaluate biliary digital imaging technology in determining the type of the intrahepatic bile duct anatomy and the transection plane of the duct in right lobe living donor liver transplantation(LDLT). Methods Mobile digital subtraction angiography was performed to show the intrahepatic bile duct anatomy of 66 liver transplant donor candidates. Combined with metal markers, the bile duct transection plane was defined. Comparing with the actual results, the effect of digital imaging technology in determining the intrahepatic anatomical variations and transection plane of the duct in LDLT was evaluated. Results Intrahepatic bile duct anatomical variations were showed in all donors by using digital imaging technology. type Ⅰ (classical type) was identified in45 cases (68.2%), type Ⅱ (with triple confluence, the simultaneous emptying of the right anterior segmental duct, right posterior segmental duct and left hepatic duct into the common hepatic duct) in 7 cases ( 10.6% ), type Ⅲ (no right hepatic duct stem, right posterior segmental duct draining into common hepatic duct) in 13 cases ( 19. 7% ), type Ⅳ (no right hepatic duct stem, right posterior segmental duct draining into left hepatic duct) in 1 case (1.5%), and type Ⅴ (complex variation ) in no case (0%). As a result, cases of type Ⅰ form a single anastomosis. In type Ⅱ, four cases formed double anastomoses, three cases formed single anastomosis with or without ductoplasty. In type Ⅲ, two anastomoses were formed in 9 cases, single anastomosis in 4 cases with ductoplasty. The case of type Ⅳ had double anastomoses. In all cases right lobe liver were harvested.Conclusions Biliary digital subtraction image combined with metal markers accurately defines intrahepatic bile duct anatomy and the transection plane, helping to reduce number of bile duct anastomosis, and contributes to safe graft harvesting.