Clinical research advances of liver transplantation for patients with familial hypercholesterolemia / 中华器官移植杂志

Familial hypercholesterolemia(FH)is an autosomal dominant disease.Homozygous FH patients tend to have a high incidence of severe arteriosclerotic cardiovascular disease during adolescence and die at ages of 20-30.Liver transplantation(LT)may correct the dysfunction of LDL receptor on hepatocytes, restore normal lipoprotein metabolism, arrest disease progression and improving patient outcomes.However, due to a great rarity of LT for FH, domestic transplantation centers lack the relevant clinical experiences.This review summarized some important issues of FH patients undergoing LT, such as indications, timing, donor sources, efficacies, complications and reusing diseased liver.The goal was to provide practical references for managing FH.

Minutes of seminar on 2023 multi-center cooperation project of liver transplantation for metastatic liver cancer in China / 器官移植

Led by Zheng Shusen, Academician of Chinese Academy of Engineering (CAE) from Zhejiang University, the first multi-center cooperation project of liver transplantation for metastatic liver cancer in China, gathering 28 liver transplantation centers nationwide, was launched in Shanghai. All participating experts conducted in-depth exchanges and discussions regarding four topics including inclusion criteria of liver transplantation for metastatic liver cancer, the risk assessment and prognostic evaluation of liver transplantation for metastatic liver cancer, perioperative medication of liver transplantation for metastatic liver cancer, and the implementation details of multi-center cooperation project. Questionnaires were distributed to reach consensus and pinpoint the directions, aiming to carry out high-quality and standardized clinical researches on liver transplantation for metastatic liver cancer in China.

Effect of cold ischemia time on early graft function and acute rejection after liver transplantation / 器官移植

Objective To evaluate the effect of different cold ischemia time (CIT) on early graft function and acute rejection (AR) after liver transplantation. Methods Clinical data of 218 donors and recipients undergoing liver transplantation were collected and analyzed. All patients were divided into three groups according to the CIT of donor liver: group A (CIT≤6 h, n=60), group B (6 h < CIT≤10 h, n=89) and group C (CIT > 10 h, n=69). Blood samples were collected on the 1, 7 and 14 d after liver transplantation. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and adenosine triphosphate (ATP) in CD4+T cells were detected. The incidence of AR and the positive rate of C4d deposition were analyzed. Results The ALT, AST and LDH levels in each group reached the peak on the 1 d after operation, and then gradually decreased. The indexes in each group were almost equivalent on the 14 d. An interaction effect existed between postoperative time and group. After liver transplantation, ATP levels in CD4+T cells were gradually increased in each group, peaked at postoperative 7 d, and then decreased gradually. An interaction effect was noted between postoperative time and group. The incidence of AR in groups A, B and C was 10%, 12% and 28%. Compared with group C, the incidence of AR in groups A and B was decreased significantly (both P < 0.05/3). The positive rate of C4d deposition in AR recipients of groups A, B and C was 1/3, 45% and 89% respectively. Compared with group C, the positive rate of C4d deposition in group A was decreased significantly (P=0.015). Conclusions The prolongation of CIT may lead to aggravation of early-stage liver function injury after liver transplantation, which is more easily to induce humoral AR.

Effect of adoptive reinfusion of Treg on immune rejection of islet allografts in mice / 器官移植

Objective To investigate the effects of adoptive reinfusion of regulatory T cell (Treg) on the recovery of islet function and graft survival time after islet allograft transplantation. Methods The diabetic model was established using C57BL/6 mice as recipients, and Balb/c mice were chosen as donors for islet allografts transplantation beneath the renal capsule. The recipient mice were divided into 3 groups and 3 mice in each group according to different processing Methods: Treg experiment group (Treg group, 1×106 Treg cells were injected via tail vein at 1 d before operation), positive control group [sirolimus (SRL) group, SRL at a dose of 300 μg/(kg·d) was intragastrically given every day from 1 d before operation] and blank control group (control group, an equivalent volume of normal saline was intragastrically given every day from 1 d before operation). Enzyme-linked immune absorbent assay (ELISA) was used to detect the changes of blood glucose and C-peptide in mice within 14 days after transplantation. In vivo imaging technique was used to dynamically monitor the survival of mice within 14 days after transplantation. Results In each group, the blood glucose levels at postoperative 3 d were significantly decreased compared with those before transplantation (all P < 0.001). At postoperative 1 d, the C-peptide levels showed an explosive rise to varying degree in each group. At postoperative 3 d, the C-peptide levels in each group were significantly higher than that before operation (all P < 0.001). At the end of the observation period at 14 d after operation, the C-peptide levels in the SRL and Treg groups were (427±50) pmol/L and (833±57) pmol/L, relatively higher than that in the control group. But the blood glucose levels were (14.5±0.5) mmol/L and (12.1±0.6) mmol/L, significantly lower than that in the control group (all P < 0.001). Compared with the SRL group, the explosive release amount of C-peptide was significantly lower, the declining trend was more remarkably stable, and the C-peptide level was considerably higher in the Treg group at the end of the observation period (all P < 0.001). At postoperative 14 d, the grafts were almost completely apoptotic in the control group, over 50% of the grafts survived in the SRL group, and over 80% of the grafts survived in the Treg group. Conclusions Adoptive reinfusion of Treg cells can effectively protect islet grafts, prolong the survival time of grafts, and maintain the normal levels of blood glucose and C-peptide in the recipient mice.

Preliminary study on the safety of liver transplantation recipients with Rh blood group mismatching / 中华器官移植杂志

Objective@#To explore the safety of liver transplantation recipients with Rh blood group mismatchming.@*Methods@#From May 2005 to December 2018, 1 546 cases of liver transplantation in our hospital were retrospectively analyzed. Among these cases, 5 cases of Rh blood group mismatched were Rh(-) recipients receiving Rh(+ ) donor liver. For each Rh blood group mismatched liver transplantation, 5 patients received the same Rh blood group liver allograft were matched according to a certain principle and were defined as Rh-mismatch group and Rh-match group respectively. The serum alanine aminotransferase (ALT), aspartate aminotransferase(AST)and creatinine(SCr)were compared between two groups at Days 7 & 14 post-operation. Serum total bilirubin(TB), gamma-glutamyl transpeptidase(GGT)were compared between two groups at Month 1, 6 & 12 post-operation. Hemoglobin (Hb)were compared between two groups Month 1, 3 & 6 post-operation. The rates of infection, vascular complications and acute rejection was also compared. Indirect antiglobulin test (IAT)was used for detecting the production of anti-RhD antibody in patients in Rh-mismatch group at Month 1, 6 & 12 post-operation.@*Results@#At the mentioned time, no significant inter-group difference existed in serum ALT, AST, SCr, TB, GGT and blood Hb levels(all P>0.05); Also, no significant difference existed in the incidence of infection, vascular complications or acute rejection(all P>0.05). In Rhmismatch group, 4 recipients received Rh(+ )RBC transfusion during perioperative period and no hemolytic anemia occurred after operation. Rh(D) antibody was negative at all timepoints.@*Conclusions@#Taking into account the rarity of Rh-negative blood group in Chinese, it is safe and feasible to carry out Rh blood group mismatched liver transplantation when donor or recipient with the same Rh blood group is not available.

Preliminary study on the safety of liver transplantation recipients with Rh blood group mismatching / 中华器官移植杂志

Objective To explore the safety of liver transplantation recipients with Rh blood group mismatchming .Methods From May 2005 to December 2018 ,1546 cases of liver transplantation in our hospital were retrospectively analyzed . Among these cases ,5 cases of Rh blood group mismatched were Rh(-) recipients receiving Rh(+ ) donor liver .For each Rh blood group mismatched liver transplantation ,5 patients received the same Rh blood group liver allograft were matched according to a certain principle and were defined as Rh-mismatch group and Rh-match group respectively .The serum alanine aminotransferase (ALT ) ,aspartate aminotransferase (AST ) and creatinine(SCr)were compared between two groups at Days 7 & 14 post-operation .Serum total bilirubin(TB) ,gamma-glutamyl transpeptidase(GGT)were compared between two groups at Month 1 , 6 & 12 post-operation .Hemoglobin (Hb)were compared between two groups Month 1 ,3 & 6 post-operation . The rates of infection ,vascular complications and acute rejection was also compared . Indirect antiglobulin test (IAT)was used for detecting the production of anti-RhD antibody in patients in Rh-mismatch group at Month 1 ,6 & 12 post-operation .Results At the mentioned time ,no significant inter-group difference existed in serum ALT ,AST ,SCr ,TB ,GGT and blood Hb levels (all P>0 .05);Also ,no significant difference existed in the incidence of infection ,vascular complications or acute rejection(all P> 0 .05) .In Rhmismatch group ,4 recipients received Rh (+ )RBC transfusion during perioperative period and no hemolytic anemia occurred after operation .Rh(D) antibody was negative at all timepoints .Conclusions Taking into account the rarity of Rh-negative blood group in Chinese ,it is safe and feasible to carry out Rh blood group mismatched liver transplantation when donor or recipient with the same Rh blood group is not available .

Preliminary observation of hepatic arterial chemoembolization combined with arsenic trioxide injection in treatment of primary liver cancer / 实用医学杂志

Objective This paper aims to observe and analyze the effect of hepatic arterial chemoemboliza-tion combined with arsenic trioxide injection in the patients with primary liver cancer.Methods This study includ-ed Ninety patients with primary liver cancer who were treated in our hospital from January 2013 to June 2016.The patients were divided into the study group and control group and the two groups were given different treatment proto-cols. The patients in the control group were treated with hepatic arterial chemoembolization and the patients in the study group were treated with arsenic trioxide injection.On the basis of the treatment effect was observed and com-pared. Results There was no significant difference between the two groups in recent curative effect(P > 0.05);the study group had higher one year survival rate than the control group(P<0.05).There was no significant differ-ence between the two groups in adverse reactions(P>0.05);the study group was superior to the control group in terms of improvement of quality of life(P < 0.05). Conclusions Hepatic arterial chemoembolization combined with arsenic trioxide injection can improve one year survival rate of primary liver cancer patients,and provide good long-term survival rate without obvious adverse reactions,and improve quality of life of patients.

Therapeutic effect of cannabidiol on methionine-choline deficient diet-induced nonalcoholic steatohepatitis in rats and its mechanism / 解放军医学杂志

Objective To observe whether treatment with cannabidiol (CBD) affect nonalcoholic steatohepatitis (NASH) induced by methionine choline-deficient diet (MCD) in rats and investigate the underlying molecular mechanism. Methods Sixty-three adult male SD rats were randomly divided in to three groups as follows: Control group (rats fed with normal diet), MCD group (rats fed with MCD and MCD+CBD group [rats fed with MCD and treated with cannabidiol, 2mg/(kg.d), i.p.]. Ten weeks later, steatohepatitis and fibrosis were evaluated by hematoxylin-eosin and Masson staining, respectively. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured by using an automatic biochemical analyzer and hepatic levels of cholesterol and triacylglycerol were determined with kits. Autophagic flux in livers was evaluated by Western blotting. Results Treatment with cannabidiol reduced ratio of liver/body weightratio (4.2%±0.6% versus 3.1%±0.6%, P<0.05), histological scores (4.7±1.1 versus 2.2±0.5, P<0.05) and fibrosis (1.4%±0.4% versus 0.8%±0.3%, P<0.05) in rat livers, lowered levels of ALT (214.5±54.1U/L versus 92.1±36.0U/L, P<0.05) and AST (175.9±55.2U/L versus 70.8±24.9U/L, P<0.05) in serum, attenuated hepatic fat accumulation (cholesterol, 182.4±42.7mmol/mg protein versus 101.0±33.8mmol/mg protein, P<0.05; triglyceride, 71.4±12.5mmol/mg protein versus 38.7±11.1mmol/mg protein, P<0.05), and down-regulated mRNA expression of Col1A1 (2.9±0.4 versus 1.6±0.3, P<0.05) in livers of rats fed with MCD. Furthermore, cannabidiol led to the LC3 turnover (LC3-Ⅱ/LC3-I, 37.1±10.8 versus 71.2±17.1, P<0.05) and p62 decrease (202.4±40.9 versus 125.8±32.7, P<0.05) in the livers of MCD-fed rats. Conclusion Treatment with cannabidiol could relieve MCD-induced NASH in rats, at least in part, by autophagic flux promotion.

Research progress of NLRP3 inflammasome in organ ischemia-reperfusion injury / 解放军医学杂志

Ischemia-reperfusion injury is a common pathophysiological process in organ transplantation,ischemic stroke and organ resection surgery,and also an important factor causing organ dysfunction and severe postoperative complications.How to avoid or mitigate organ ischemia-reperfusion injury has always been a research hotspot.NLRP3 Inflammasome has been considered to be an important link in inflammatory response.It has an indispensable role in maturation process of IL-lβ and IL-18.We reviewed the research in recent yeas about the role of NLRP3 Inflammasome in organ ischemia-reperfusion injury in this paper.

Effect of curcumin on autophagy and inflammatory response in mice subject to renal ischemia reperfusion injury / 中华器官移植杂志

Objective To investigate the effect of curcumin on autophagy and inflammatory response in mice subject to renal ischemia reperfusion.Method Forty male C57BL/6 mice were randomly divided into four groups (n =10 each):sham-operated (SO) group (Abdominal incision was made to expose the kidneys,bilateral renal pedicle dissociated and the abdomen sewed),ischemia reperfusion (IR) group,curcumin (CM) group (given CM 10 mg/kg) and 3-methyladenine (3-MA) group (given 3-MA 15 mg/kg).Six and 24 h after reperfusion,renal function was tested by determining the serum creatinine (Scr) and blood urea nitrogen (BUN) levels,and the morphological changes in the kidney tissue were observed.The expression of LC3,Beclin 1,Rab7 and LAMP2 in kidney tissue was detected by fluorescence quantitative RT-PCR and Western blotting.Fluorescence quantitative reverse transcription PCR and enzyme-linked immunosorbent assay were used to examine the expression of IL-6,IL-10,IL-17 and TNF-α in kidney tissue and serum.Result As compared with IR group and 3-MA group,the Scr and BUN levels in the CM group were significantly decreased (P＜0.01),and the renal morphological changes were improved significantly (P＜0.01).The mRNA and protein expression of LC3,Beclin 1,Rab7 and LAMP2 was significantly increased in kidney tissue,and the expression of IL-6,IL-17 and TNF-α was reduced,while IL-10 was increased (P＜ 0.01) in the CM group as compared with IR group and 3-MA group.Conclusion Curcumin possesses a protective effect against renal ischemia reperfusion injury in mice,which is probably mediated by promoting autophagy and subsequently inhibiting inflammatory response.

Prognostic analysis of liver transplantation in treating patients with end-stage autoimmune liver disease / 器官移植

Objective To investigate the prognosis of patients underwent liver transplantation (LT) for end-stage autoimmune liver disease (AILD). Methods Clinical data of 48 patients with end-stage AILD undergoing LT from May 1996 to April 2013 in Affiliated Changzheng Hospital of the Second Military Medical University were analyzed retrospectively. The postoperative cumulative survival rates of the recipients were calculated,and the cause of death was analyzed. The postoperative rejections,new-onset viral hepatitis and AILD recurrence were analyzed. Results In 48 AILD recipients,38 cases survived and the postoperative 5-year cumulative survival rate was 76%. Causes of death for the 10 dead cases were multiple organ failure, liver graft failure,sepsis,pulmonary infection,hemorrhage,hepatic artery embolization and renal failure. In 48 AILD recipients,9 cases (19%) suffered acute rejection after operation,3 cases suffered new-onset hepatitis B infection in 1-2 years after operation,2 recipients suffered primary disease (primary biliary cirrhosis)recurrence 2 years after operation and all survived for a long term after positive treatments.Conclusions Most liver transplant recipients with end-stage AILD can obtain a long-term survival. Attentions should be paid on the immunosuppressive regimens in early period after LT,prevention of infection,rejection and postoperative new-onset viral hepatitis,timely diagnosis of primary disease recurrence.

The related perioperative risk factors of early acute lung injury after orthotopic liver transplantation / 中华器官移植杂志

Objective To analyze related perioperative risk factors of acute respiratory distress syndrome (ARDS) early after orthotopic liver transplantation (OLT).Methods The cases from the recipients having undergoing OLT,aged from 15 to 65 years and having no chronic respiratory diseases and hyoxemia were collected.The exclusive criteria were as follows:(1) the patients dead or automatic discharging at the day after the OLT or during the OLT; (2) the patients suffered from severe surgical technic complications; (3) initial poor graft function occurred; (4) marginal donor; (5) pulmonary wedge pressure (PAWP)＞ 2.394kPa.251 patients were enrolled in this analysis,who were grouped according to whether they developed ARDS (group B) or not (group A) in the first postoperative day.The analyzed factors were as follows:(1) the sex,age and weight of the recipients; (2) preoperative variables of recipients:Child-Pugh and Model for end-stage liver disease (MELD) score,left vent ricular ejection fractions,oxygenation index,the serum levels of creatinine,BUN,TB,albumin,prealbumin,fibrinogen and hemoglobin,white blood cells (WBC),platelet count and international normalized ratio (INR) ; (3) the variables of donator:age,the time of warm and cold ischemia; (4) the intraoperative variables:operative time,anhepatic phase,the volumes of hemorrhage and blood-transfusion (red cell suspension and plasma),transfusion volume; (5) postoperative variables of recipients:the serum levels of creatinine,blood urea nitrogen (BUN),total bilirubin (TB),albumin,alanine aminotransferase (ALT),sodium and potassium,fibrinogen and hemoglobin,WBC,platelet count and INR.Results The mild ARDS incidence early after OLT was 25.5 ％ (65/251) and the moderate or severe was 4.8％ (12/265).Single factor analysis showed that the factors having significant difference between group A and group B were as follows:the age of the recipients,preoperative variables (Child-Pugh and MELD score,the preoperative serum levels of BUN,TB,prealbumin,fibrinogen and hemoglobin,WBC,platelet count and INR),the intraoperative variables (the volumes of hemorrhage and blood-transfusion including red cell suspension and plasma) and the postoperative variables (the serum levels of BUN,TB,sodium,fibrinogen and hemoglobin,WBC,platelet count and INR).The significant factors were put to the analysis of LOGISTIC regression,and the results showed that the age of recipients,preoperative Child-Pugh score,BUN and INR,intraoperative hemorrhage volume,postoperative serum level of sodium were the independent risks contributing to ARDS.Conclusion The mild ARDS incidence early after OLT was high but the the moderate or severe incidence was low.The age of recipients,preoperative Child-Pugh score,BUN and INR,intraoperative hemorrhage volume and postoperative serum level of sodium may be the main risk factors to lung injury after OLT.

Immunosuppressant withdrawal for the management of severe infection in liver transplantation recipients / 中华普通外科杂志

Objective To explore the effectiveness and safety of temporary immunosuppressant withdrawal for the management of severe infection after liver transplantation.Methods Fifty-one patients with severe infection after liver transplantation were divided into control group (24 cases) and withdrawal group (27 cases ) according to the immunosuppression protocol.In the withdrawal group, the immunosuppressive drugs were temporarily suspended according to ATP values of CD4 + T cell and CD4 + T lymphocyte subsets counting until infection was controlled.The liver function,the incidence of acute rejection and the graft survival rate were monitored during the process.The side effects were observed.Result Severe infection was cured in 39 patients.There were 9 deaths in the control group in which the immunosuppressant was continued during the course of infection and 3 in the withdrawal group,respectively.The median suspension of immunosuppressant in trial group was ( 15.5 ± 4.8 ) d ( 6 ～ 22 d) ; CD4 + T lymphocyte subsets counting rose from (65.60 ± 32.58)/μl to (103.04 ± 12.39)/μl,ATP values of CD4 + T cell rose from (79 ±23) μg/L to ( 112 ± 11 ) μg/L; meanwhile,the temperature dropped from (38.3 ± 1.2) ℃ to (36.4 ± 1.1) ℃,WBC dropped from (15.7 ± 4.4) × 109/L to (6.3 ± 3.8) × 109/L,CRP dropped from ( 153.4 ± 37.1 ) mg/L to ( 16.5 ± 4.8) mg/L.During the course of treatment and follow-up,liver function of patients in the trial group remained normal and no acute rejection occurred.Compared with the control group,the temperature recovery time in the trial group was shorter ( respectively F =5.32,8.37,9.12,all P ＜ 0.05) and the therapeutic outcome was better.Conclusions The cellular immune function test could be evaluated according to the ATP values of CD4 + T cell and CD4 + T lymphocyte subsets counting.For severe infection after liver transplantation, anti-infection treatment and simultaneously withdrawing immunosuppressants help to control the infection.

Clinical research of Hangzhou domestic tacrolimus in liver transplantation / 中华器官移植杂志

ObjectiveTo demonstrate the efficacy and safety of Hangzhou tacrolimus capsule (Saishi Tac capsule,Hangzhou Zbongmei Huadong Pharmaceutical Co.Ltd,China) in Chinese liver transplant recipients.MethodsMulticenter,randomized open-labeled,prospective controlled clinical trial was performed in de novo Chinese liver transplant recipients.According to inclusive and exclusive criterion,83 liver recipients from 11transplant centers were enrolled.The recipients accepted Saishi Tac capsule,mycopheolate and steroid 48 h post-operation.The initial dose of Tac was 0.1-0.15 mg kg-1day-1and C0 was 8-12 ng/ml in the first 60 days,followed by 5-10 ng/ml until the terminal observation time poiut (12 weeks after transplantation).The efficacy and safety were estimated during the period.The primary efficacy endpoint of the study was the incidence of biopsy-confirmed acute rejection.Graft survival was the secondary endpoint.Safety was assessed by monitoring laboratory parameters and adverse events reported over the course of the study,such as infection,renal damage,hypertension,hyperlipema and diabetes mellitus and other adverse affairs.ResultsThe dose of Tac at 1st,2nd,4th and 8th week post-operation was (4.1±1.9),(4.5±2.1),(4.5±2.1),(4.4±1.8) and (4.1±2.1) mg,and correspondjng values to the C0 were (8.1±4.5),(8.9±4.5),(8.8±4.3),(8.8±4.1) and (8.0±2.8) ng/ml.During 12 weeks of follow-up,the incidence of biopsy-confirmed acute rejection was 4.8％ (4/83),and all of cases were reversed by implosive therapy.The survival rate of graft hver was 100％.The incidence of lung infection and diabetes mellitus was both 6.02％.ConclusionSaishi Tac capsule was safe and effective to Chinese liver transplant recipients.

A single-center retrospective study on calcineurin inhibitors withdraw and conversion to sirolimus for drug adverse reactions / 中华器官移植杂志

Objective To report the results of a single-center, retrospective study on the effect of calcineurin inhibitors (CNI) withdraw for controlling infections and conversion to sirolimus (SRL)for ameliorating renal dysfunction. Methods A total of 947 liver transplant cases from 2002 to 2010were divided into two eras (Jan. 2002 to Dec. 2007 and Jan. 2008 to Dec. 2010). There were 234cases of infections after liver transplantation (LT) in the first era and 101 cases in the second era. And of 329 cases of CNI-related renal dysfunction after LT in two eras, 40 cases (converting group) had converted CNI to SRL, while 289 cases (reducing group) adopted protocol of CNI reducing and mycophenolate mofetil (MMF) raising. Results CNI-based IS took up 95.8 %, 95. 3 %, 97. 5 % of the IS protocols with recipient survival time longer than 1, 3, and 5 years. The primary cause for CNI withdraw was infection (88. 2 %, 15/17) in the second era, and renal dysfunction for conversion to SRL in the two eras (83. 3 %, 40/48). In the second era, 14. 9% (15/101) of the cases of infections after LT experienced CNI withdraw. Of the 15 patients, 11 had effectively controlled the infection (77. 3 %) while rejection rate was 6. 7 % (1/15). The cumulative survival rate of the second era was significantly higher than the first era (P＜0. 05). The glomerular filtration rate (GFR) of converting group at 6th week and 6th month was statistically elevated as compared with that before conversion,respectively (1.28 ± 0. 31, 1.36 ± 0. 32 mL/s vs. 0. 82 ± 0. 24 mL/s, P＜0. 05). Six months after CNI adjustments, survival rate of converting group and reducing group was 85. 0% and 83. 7 %,respectively (P＞0. 05). Conclusion Reducing or even short-term withdraw of CNI may allow the better control of infections after LT, and the conversion from CNI to SRL can ameliorate the CNIrelated nephrotoxicity. These individually tailored IS protocols will benefit the long term survival for LT.

A randomized trial on the efficacy and safety of Advagraf vs tacrolimus in prevention of acute liver allograft rejection / 中华器官移植杂志

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.

Dynamic changes of cellular immune function and individualized adjustments of immunosuppressant for the management of severe infection after liver transplantation / 中华器官移植杂志

Objective To explore the dynamic changes of the cellular immune function in severe infection after liver transplantation, and to guide the individualized immunology adjustment. Methods 378 cases of livertransplantation were analyzed retrospectively. Seventy-four cases (infection group) suffered serious infection, including 54 cases cured (cure group), 20 cases died (death group). Fifty cases without infection and rejection were randomly selected as control group (stable group). According to the individualized adjusting proposal of immunosuppressants, 74 patients with severe infection were divided into two groups: traditional (T) group and individualized (Ⅰ) group. The general condition, recovery rate and change of cellular immune function pre- and post-treatment were analyzed. Results The preoperative MELD score and the intraoperative blood loss in infection group were significantly higher than stable group, and those in death group were higher than in cure group. CD4+ T lymphocyte counts and lymphocyte counts in stable group were increased significantly from first week post-operation to discharge. The two indicators in infection group at first week postoperation and the onset of infection were lower than in stable group (P<0. 01). In cure group after infection was controlled the two indicators were higher than at first week post-operation and the onset of infection (P<0. 01), while in death group they were reduced up to death (P<0. 05). There was no significant difference in age, preoperative MELD score and the immune function indicators both at first week post-operation and the onset of infection between T group and Ⅰ group, except the intraoperative blood loss in Ⅰ group was greater than in T group. The recovery rate in Ⅰ group (90. 5 %)was higher than in T group (66.0 %). Conclusion Individualized adjustments of immunosuppressants guided according to the dynamic changes of cellular immune function helped to improve the prognosis of severe infection after liver transplantation.

Cellular immunology function test and individualized immunology adjustment of pan-drug resistant Acinetobacter baumannii infected patients after liver transplantation / 中华器官移植杂志

Objective To explore the monitoring and the individualized adjustment of cellular immunology function in the recipients infected with pan-drug resistant Acinetobacter baumannii(PDR-Ab)after liver transplantation.Methods We retrospectively summarized the infection and the prognosis of PDR-Ab in 299 cases of liver transplantation performed from Jan.2008 to May 2010.The absolute number of T lymphocytes and ATP level within CD4+ T cells were monitored,and T cell immunology function(TCIFS)was scored.According to different immunology adjusting proposals,14 cases of PDR-Ab infection were divided into 2 groups:(1)traditional group,routine anti-infective therapy;(2)individualized group.Individualized immunology adjustment was made according to the score of TCIFS besides routine therapy.Results There was no significant difference in age,MELD and Child-pugh score between two groups.The peri-operative bleeding volume in individualized group was more than that in traditional group(P<0.01).There was no significant difference in TCIFS score between two groups at 1st week after transplantation and the onset of the PDR-Ab infection.However,the score in individualized group was apparently higher than that in traditional group when anti-infection therapy ended(P<0.05).The difference in the recovery rate between two groups was significant(P<0.05).No rejection happened in two groups.Conclusion It is an effective way to decrease the mortality of PDR-Ab infection after liver transplantation that the individualized adjustment of immunosuppression protocols is guided by grading quantitatively the cellular immunology function according to the absolute number of T lymphocytes and ATP level within CD4+ T cells.

The relationship between ImmuKnow value of cellular immune function and peripheral white blood cells count and T-lymphocyte after liver transplantation / 中华普通外科杂志

Objective To explore the relationship between peripheral differential blood count and ATP value in Cell CD4 + T tested by ImmuKnow method in liver transplants. Methods In this study 49recipients after classic orthotopic liver transplantation (OLT) were enrolled. In a period from two weeks to two months after transplantation when all were free of glucocorticoid. Blood were sent for WBC differential samples count and ATP value in Cell-CD4 + T tested by ImmuKnow method via SPSS17. 0 software. Five more samples were selected randomly for duplicated testing of the indices in Week2, 3, 4,6 and 8 after the transplanting operation to further verify the relativity. Results White blood cell count has the highest relativity with ImmuKnow ATP value at 0. 821. The 5 recipients were repeatedly tested for ImmuKnow ATP values that were found positively correlated to cell count with a coefficient of over 0. 5. Conclusions The peripheral leukocyte count in early stage after liver transplantation is in positive correlation with ATP value in Cell CD4 + T, and the changes of numeration of leukocyte reflect changes of ATP value.

Salvianolate induces apoptosis of human hepatoma SMMC-7721 cells through mitochondrial pathway / 中国肿瘤生物治疗杂志

Objective: To explore the apoptosis-inducing effect of salvianolate on hepatoma SMMC-7721 cells and the underlying mechanism. Methods: SMMC-7721 cells were co-cultured in vitro with different concentrations (0.5, 1, 2 mg/ml) of salvianolate for 24 h. The apoptotic SMMC-7721 cells were examined by flow cytometry, and the changes of mitochondrial transmembrane potential were examined by mitochondrial transmembrane potential JC-1 kit. The activities of caspase-8, caspase-9, and caspase-3 were detected by spectrophotometry in the hepatoma SMMC-7721 cells after co-cultured with 1 mg/ml salvianolate. The changes of apoptotic SMMC-7721 cells induced by salvianolate in the presence or absence of caspase-9 inhibitor or caspase-3 inhibitor were measured by flow cytometry. The expressions of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2 were detected by Western blotting analysis. Results: Salvianolate significantly induced apoptosis of hepatoma SMMC-7721 cells (P<0.05), and the decline of mitochondrial membrane potential increased with the increase of salvianolate concentration (P<0.05). The activities of caspase-9 and caspase-3, but not caspase-8, were increased in hepatoma cells after treatment with 1 mg/ml salvianolate for 24 h (P<0.05). The apoptosis-inducing effect of salvianolate was significantly decreased in the presence of caspase-9 or caspase-3 inhibitors (P<0.05). Western blotting results showed that salvianolate increased pro-apoptotic protein Bax expression and decreased anti-apoptotic protein Bcl-2 expression. Conclusion: Salvianolate can induce the apoptosis of human hepatoma SMMC-7721 cells in a dose-dependent manner, which is probably mediated by mitochondrial apoptosis pathway.