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 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 summary therapeutic method for delayed portal vein thrombosis after liver transplantation. Methods In 3100 cases undergoing cadaveric whole liver transplantation in a single center, there were 12 cases of delayed portal vein thrombosis after liver transplantation.Average occurring time was 29. 8 months after liver transplantation. Among these 12 patients, 2 cases were complicated with severe biliary complication (intrahepatic stricture) , 2 cases presented with liver failure of transplanted liver, and one case had portal vein compression by hepatic hilum tumor under the image examination, who received liver re-transplantation; two patients presented upper gastrointestinal bleeding, and they experienced endoscopic ligation and sclerotherapy respectively; the rest five patients without any clinical presentation were subjected to anticoagulation and antiplatelet therapy. Results Among 12 cases, 8 patients survived by the time of follow-up, including two patients undergoing re-transplantation; one patient lost follow-up. The liver function tests of the patients who survived were all normal. Conclusion The individualized therapeutic methods should be adopted for the patients with delayed portal vein thrombosis after liver transplantation.

ObjectiveTo investigate the effect of living donor right liver graft transplantation (LDLT) with middle hepatic vein (MHV) on the early congestion and regeneration of the donor remnant liver.MethodsBetween August 2008 and August 2009,28 LDLT were performed with 11 LDLT without MHV (group A) and 17 LDLT with MHV (group B).The donor operative time,intraoperative blood loss,postoperative hospital stay,bilirubin,INR,and ALT level were recorded in detail.We measured the volume of remnant liver by means of CT scan 2 weeks after operation and compare the degree of congestion and regeneration of the remnant liver between the two groups.ResultsThere were 10 cases in group B and 0 cases in group A suffering from congestion at segment Ⅳ,and the difference was significant(P =0.006).In group B,6 cases in type Ⅰ and 4 cases in type Ⅱ developed congestion at segment Ⅳ,and the difference was significant(P=0.035).Two weeks post operation,the volume of segment Ⅳ in group B was smaller than in group A(P=0.005).The regeneration rate of segment Ⅳ in group B was smaller than in group A (P =0.007),on the contrary,the regeneration rate of segment Ⅰ - Ⅲ in group B was larger than in group A( P =0.008 ).But the regeneration rate of remnant liver was the same in both groups (P =0.63 ).ConclusionsThe right lobe hemihepatectomy with MHV does not damage the early liver function of the donor significantly.The segment Ⅳ of the remnant liver suffered from congestion and impeded the regeneration,but was compensated by the regeneration of segments Ⅰ - Ⅲ.

Objective To summarize our experience of harvesting and using the organs of donors after cardiac death.MethodsForm March 2010 to October 2011,56 potential donors were diagnosed with cardiac death,who conformed to the classification of Maastricht Ⅲ criteria.There were 40 failure cases whose family refused to donate,and one failure case who suffered from serious infection.Finally,the success ratio of donation after cardiac death was 26.8％ (15/56).Twelve livers and 22 kidneys were transplanted into 12 and 20 recipients respectively.ResultsTwelve cases of liver transplantations had acceptable outcomes. The grafts of 4 cases out of 20 cases of kidney transplantations were removed after transplantation,and other recipients had acceptable outcomes.ConclusionCitizens organ donation after cardiac death can expand the number of suitable organs,but we need to strictly control the criteria for potential donors.

Objective To investigate the experience of treating Budd-Chiari syndrome through orthotopic liver transplantation.Methods The clinical data of LTx performed on 9 patients with Budd-Chiari syndrome from December 2003 to April 2010 were retrospectively analyzed. We summarize the preoperative image and surgical experience,and observe the occurrence of postoperative complications and survival. Results Budd-Chiari syndrome was diagnosed in 9 patients by the preoperative abdominal CT enhancement and vascular reconstruction,and cavity venography was done to observe obstruction and sub-type of CAVA vein.All 9 patients were subjected to cadaveric liver transplantation.Eight cases accepted classic non bypass type,and one accepted living related right lobe liver transplantation. Postoperative triple immunosuppressive regimen included tacrolimus,mycophenolate mofetil,and hormone.The average follow-up periods for all these 9 patients were 32.8 months (13 to 61 months). One patient died from the tumor recurrence at 35th month after the operation.Two patients received re-transplantation for the lost of the graft.One recipient received the donor liver with medium steatosis,and the re-transplantation was performed on the12th day after the first transplantation due to the primary non function of the graft.The other one received the secondary liver transplantation at 6th month after the first transplantation due to the biliary complication and died from the liver tumor recurrence. Among all the 9 cases,seizure disorder (1 case),dysfunction of duodenal papillary muscle (1 case) and small-for-size syndrome (one case) occurred after the operation.Pulmonary infection occurred in 4 cases:3 cases due to the bacterial infection and 1 due to the fungal infection. Neither outflow obstruction nor the recurrence of the Budd-Chiari syndrome occurred in this study.The 1- and 2-year survival rate after the operation was both 100％,and 3-year survival rate post-transplantation was 88.9％ (8/9).Conclusion Liver transplantation can be the ideal treatment to the Budd-Chiari syndrome based on the definite clinical diagnosis,accurate imaging evaluation and eligible modus operandi.

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.