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 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 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.

Objective To investigate the characteristics of liver function recovery in steatotic liver graft transplantations.Method From August 1st 2013 to July 20th 2014,a prospective clinical cohort study of liver transplantations was performed in Tianjin First Central Hospital.Multiple linear regression analyses were made for related factors with the degree of donor liver steatosis and the average total bilirubin (TBil) levels on the post-operative day 6 to 8,week 4,and month 3 and 6,respectively.Result Of 82 cases used for analysis,there were 28 cases of mild steatotic grafts and 54 cases of non steatotic grafts.The multiple linear regression analysis revealed the average TBil level on the post-operative day 6 to 8 was the only one index related with the degree of graft steatosis.By the same means,recipient age,the aspartate aminotransferase (AST) level on the post-operative day 1,the average AST level on the post-operative day 2 to 3,and the degree of graft steatosis were associated with the average TBil level on the post-operative day 6 to 8.The AST level on the postoperative day 1,the average AST level on the post-operative day 2 to 3,and the degree of graft steatosis were associated with the average TBil level on the post-operative week 4.But only the AST level on the post-operative day 1 and the average AST level on the post-operative day 2 to 3 were associated with the average TBil level on the 3th and the 6th month post-operation.Conclusion Mild steatotic liver graft can result in increased TBIL level within perioperative period,but the graft function is not affected by it.The average AST level on the post-operative day 2 to 3 can effectively predict the prognosis of the graft.Objective Methods Results Conclusion

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 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.

Objective To evaluate the effect of aged cadaveric donor liver on long-term survival of liver transplant recipients.Methods Patients who underwent first time liver transplantation from cadaveric donor aging above 40 years were studied.Those patients were divided into donor age ＜ 50 group and age ≥ 50 group.Data for donor graft,recipient perioperative condition as well as long-term survival of recipients were compared between the two groups.Results There were 21 recipients receiving liver graft from a donor aging ≥ 50 (54.6-± 3.9) years.58 cases were given a liver graft from a donor aging ＜ 50 years (42.6 ± 2.9).The overall donor graft conditions were not different between the two groups (P ＞ 0.05).However,the median amount of operation time in donor age ≥50 group was longer than that in age ＜ 50 group (9.5 h vs.8.0 h,Z =-1.994,P =0.046).Median red blood cell (RBC) transfusion volume was greater in the age ≥50 group than that in age ＜50 group (1 000 ml vs.800 ml,Z =-2.593,P =0.010).During the follow-up,graft survival rates in 1,3 and 5 years were 74％,55％,55％ in donor age ≥50 group and 87％,66％,63％ in donor age ＜ 50 group,respectively (Z =0.903,P =0.342).Conclusions Use of aging cadaveric donor liver expandes donor pool,and is as well as safe,not hindering in graft's long term functions.

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.