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OBJECTIVES@#Hepatic fibrosis is a serious pathological consequence of chronic liver disease. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant after organ transplant. However, the relationship between MMF and hepatic fibrosis remains unclear. This study aims to explore the effect of MMF on hepatic fibrosis in mice and the potential mechanism.@*METHODS@#A total of 24 mice (male, 8-week old, C57BL/6) were randomly divided into a control group, a MMF group, a carbon tetrachloride (CCl4) group and a CCl4+MMF group (n=6 in each group). After the mice were sacrificed, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected. The liver tissues were taken up for Masson staining and collagen I (COL1) immunohistochemistry. The levels of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were detected by Western blotting. Finally, the levels of mRNA for TGF-β1, α-SMA, and COL1 were detected using real-time PCR.@*RESULTS@#Compared with the CCl4 group, the ALT and AST levels were lower (both P<0.05), the degree of liver fibrosis was alleviated, and the deposition of COL1 in the liver was significantly decreased (P<0.01) in the CCl4+MMF group. Compared with the CCl4 group, the protein expression levels of TGF-β1 and α-SMA were significantly decreased (both P<0.05) and the relative expression levels of TGF-β1, α-SMA and COL1 mRNA in the liver were significantly decreased (all P<0.05) in the CCl4+MMF.@*CONCLUSIONS@#MMF could reduce CCl4-induced hepatic fibrosis, which might be related to the inhibition of TGF-β1. This study is expected to provide a target for the treatment of hepatic fibrosis.
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Male , Animals , Mice , Mice, Inbred C57BL , Mycophenolic Acid/therapeutic use , Carbon Tetrachloride/toxicity , Transforming Growth Factor beta1/genetics , Liver Cirrhosis/drug therapy , RNA, MessengerABSTRACT
Diabetes mellitus is one of the most common complications after liver transplantation. The survival rate of recipients after liver transplantation with diabetes mellitus and the long-term survival rate of grafts are significantly lower than those of their counterparts without diabetes mellitus. In recent years, diabetes mellitus after liver transplantation has attracted widespread attention along with the rapid development of liver transplantation in China. Although post-transplantation diabetes mellitus (PTDM) has been extensively investigated in the past two decades, multiple problems remain to be further resolved. The study was designed to review the latest research progress upon diabetes mellitus after liver transplantation, covering the definition and diagnostic criteria of PTDM, risk factors, prevention and treatment of diabetes mellitus after liver transplantation, aiming to deepen the understanding of diabetes mellitus following liver transplantation, deliver effective prevention and management, improve the long-term survival rate and enhance the quality of life of the recipients.
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Renal transplantation is one of the most effective treatment methods for end-stage renal diseases. However, some recipients present with fatigue symptoms after renal transplantation. Fatigue not only affects the quality of life, but also reduces the compliance of recipients with immunosuppressive agents. To strengthen the attention of medical staff to the fatigue, make early diagnosis and deliver effective interventions for renal transplant recipients, the current situation, risk factors and intervention methods of fatigue in renal transplant recipients were reviewed in this article.
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The positive human leukocyte antigen (HLA) antibody present in kidney transplant recipients affects both surgery and rejection, and also affects the long-term survival of the transplanted kidney. During the third kidney transplant, bilateral axillary fossa and iliac vessel were destroyed. It was very difficult for selection or separation of surgical vessels because the adhesions and scar formation was easy to damage blood vessels and intestinal tubes. A case with strong positive HLA antibody undergoing the third kidney transplant in our hospital was successfully solved the problems, such as less transplant space and vascular scar adhesion. Rituximab, rabbit anti-human thymocyte immunoglobulin, and methylprednisolone treated-antibodies were used in the operation. The immune function test was used to develop individualized treatment after the operation. The postoperative creatinine and urine volume tended to be stable, and the 16-month follow-up renal function was good.
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Humans , Antibodies , Kidney , Kidney Diseases , General Surgery , Kidney Transplantation , Nephrectomy , RituximabABSTRACT
Objective To explore the effects of WeChat-based peer supports upon medication adherence and quality-of-life in liver transplant recipients .Methods A total of 63 patients with liver transplantation were conveniently divided into intervention group (n=32) and control group (n=31) depending upon their different follow-up periods .In control group ,routine outpatient health guidance was offered while intervention group received 6-week WeChat-based peer supports . Medication compliance and quality-of-life of two groups were evaluated at Month 3/6/12 post-intervention . Results At Month 3 post-intervention ,as compared with control group ,only non-punctual medication improved significantly in intervention group (P<0 .01);at Month 6 post-intervention ,all aspects of drug adherence improved in intervention group (P< 0 .05) ,at Month 12 post-intervention ,drug adherence ,non-punctual medication and missed dosing improved in intervention group ( P> 0 .05 ) . However , inter-group quality-of-life was not statistically significant at Month 3/6/12 post-intervention .Conclusions WeChat-based peer supports may partially improve the immediate compliance of patients with liver transplantation .However ,long-term outcomes and effects on quality-of-life are worth further researches .
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Objective To investigate the clinical efficacy of vena cava-atrium anastomosis liver transplantation (VCAALT) for Budd-Chiari syndrome (BCS).Methods The retrospective descriptive study was conducted.The clinicopathological data of 18 BCS patients who underwent VCAALT in the Zhongnan Hospital of Wuhan University (6 cases),the Third Xiangya Hospital of Central South University (8 cases) and Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (4 cases) from May 1996 to December 2012 were collected.All the 18 patients were males,aged from 29 to 61 years,with an average age of 42 years.According to characteristics and invasion extent of hepatic vein and vena cava after preoperative examinations,patients were performed different surgical procedures of VCAALT,including bridge piggyback liver transplantation (BPBLT),hanging atrium liver transplantation (HALT) and cava vena resection bridge liver transplantation (CVRBLT).Observation indicators:(1) surgical and postoperative situations;(2) typical case analysis;(3) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect patients' survival up to December 2018.Measurement data with normal distribution were represented as Mean±SD and measurement data with skewed distribution were described as M (range).Results (1) Surgical and postoperative situations:of 18 patients,11 underwent BPBLT,3 underwent HALT,4 underwent CVRBLT.The operation time and volume of intraoperative blood loss were (6.0± 1.3)hours and (1 264±435)mL.One patient died of bilateral pulmonary diffuse inflammation and sepsis due to severe infection.The duration of postoperative hospital stay was (18±5) days.(2) Typical case analysis:one 47-year-old male BCS patient was detected retrohepatic vena cava plaques and thrombus and hepatic venous thrombus by exploratory laparotomy,and underwent BPBLT.A 43-year-old male BCS patient was detected hepatic and retrohepatic vena cava plaques,thrombus,concomitant cavernous transformation,and underwent HALT.A 32-year-old male BCS patient was detected plaques and thrombus with red thrombus in the hepatic vein,from right renal vein to right atrium,and underwent CVRBLT.All the 3 patients underwent VCAALT successfully with a satisfactory recovery.(3) Followup situations:18 patients were followed up for 3.0-60.0 months,with a median time of 51.7 months.During the follow-up,3 patients died of acute rejection,biliary complications and chronic graft dysfunction at 1,3,5 years postoperatively.The 1-,3-,5-year survival rates were 16/18,15/18,14/18,respectively.Conclusion Different surgical procedures of VCAALT for BCS are selected according to different situations of patients,which are safe and feasible with a satisfactory efficacy and beneficial to long-term survival of patients.
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Orthotopic liver transplantation (OLT) was first implemented by Starzl in 1963.With the development of liver transplantation,Tzaris was the first to report piggyback liver transplantation (PBLT) in 1989.The fundamental difference between OLT and PBLT:end to end vascular anastomosis between the donor and recipient is performed after diseased liver resection with the posthepatic inferior vena cava in OLT,while PBLT is to preserve the recipient's hepatic vein and end to end vascular anastomosis between interior vena cava of donor and shaped hepatic vein is performed.However in the clinical practice,the above two techniques cannot meet the needs of clinical liver transplantation technology.Since 1993 the author has implemented a series of improvements in liver transplantation technology based on PBLT and performed ameliorated piggyback liver transplantation (APBLT).This article focuses on the technical characteristics and clinical application of APBLT.
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Objective To investigate the correlation between red cell volume distribution width (RDW) and the mortality rate of acute respiratory distress syndrome (ARDS) patients after renal transplantation. Methods Clinical data of 106 ARDS patients undergoing renal transplantation were retrospectively analyzed. According to RDW, all patients were assigned into the normal (≤15.0%, n=68) and increasing RDW groups (>15.0%, n=38). Baseline data and the incidence of adverse events were statistically compared between two groups. Kaplan-Meier survival curve was adopted to compare the 50 d-mortality rate between two groups. Cox's proportional hazards regression model was utilized to identify the risk factors of the mortality of ARDS patients. Results Among 106 patients, the 50 d-mortality rate was calculated as 43.4% (46/106). The sequential organ failure assessment (SOFA) score, serum creatinine, hemoglobin and platelet count significantly differed between two groups (all P<0.05). In the increasing RDW group, the 50 d-mortality rate and the incidence of infectious shock were significantly higher than those in the normal RDW group (both P<0.05). Kaplan-Meier survival curve demonstrated that the 50 d-mortality rate significantly differed between two groups (P<0.01). Cox's proportional hazards regression model univariate analysis revealed that hemoglobin level<100 g/L, serum creatinine>133 μmol/L, platelet count<100×109/L, severe ARDS and RDW>15.0% were the potential risk factors of the 50 d-mortality rate in ARDS patients (all P<0.05). Multivariate analysis demonstrated that severe ARDS [odd ratio (OR)=12.77, 95%confidence interval (CI) 11.63-15.39, P<0.001] and RDW>15.0% (OR=2.01, 95%CI 1.02-3.94, P<0.043) were the independent risk factors of the 50 d-mortality rate in ARDS patients. Conclusions RDW elevation is correlated with the severity of disease and 50 d-mortality rate in ARDS patients following renal transplantation. RDW can serve as a clinical parameter to predict the prognosis of ARDS patients after renal transplantation.
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Objective To observe the clinical efficacy and safety of direct-acting antiviral agents(DAAs)in the treatment of hepatitis C after renal transplantation. Methods Six patients were complicated with hepatitis C virus(HCV) at 8 to 43 months after renal transplantation with a median time of 19 months. Prior to treatment, the virus load was detected from 4.03×103 to 8.18×107 IU/mL. Four cases were administered with tacrolimus(FK506)+mycophenolate mofetil(MMF)+prednisone(Pred), and the remaining 2 received cyclosporin(CsA)+MMF+Pred. The serum creatinine level was lower than 200μmol/L. The amount of urine and body weight remained stable. No severe mental irritation or trauma history wasreportedwithin6monthsbeforeantiviraltherapy.SixpatientsdidnotreceivegenotypetestofHCVbeforeDAAstherapy. Fourpatientswereadministeredwithsofosbuvir,1withsofosbuvir+ledipavirand1withsofosbuvir+daclatasvirfor12weeks. The complete blood cel count, serum transaminase level, creatinine level and blood concentration of immunosuppressive agents were measured each week and serum HCV RNA level was quantitatively detected every 4 weeks. Results Among 6 patients, 5 were negative for HCV at 4 weeks after DAAs therapy and obtained sustained virological response(SVR)after DAAs treatment. One case administered with sofosbuvir alone was positive for HCV after DAAs therapy. The patient was infected with genotype 5 HCV. After 12-week administration of sofosbuvir+daclatasvir, the patient was negative for HCV and obtained SVR. No significant changes were observed in complete blood cel count, serum transaminase level, creatinine level and blood concentration of immunosuppressive agents. Adverse reactions included evanescent eruption in 1 case and mild dizziness in 1 case. Conclusions DAAs treatment is an effective and safe approach for patients with stable renal function after renal transplantation. Combined use of sofosbuvir+daclatasvir is recommended as the optimal therapy.
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Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.
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Objective To compare three different types of donor livers (C-Ⅰ,C-Ⅱ,C-Ⅲ) in clinical efficacy,complications and survival rate of liver transplantation.Methods Using the retrospective descriptive study method,the clinical data of 422 patients undergoing liver transplantation,including 124 cases of C-Ⅰ,81 cases of C-Ⅱ and 81 cases of C-Ⅲ in recent 6 years (from June 2010 to June 2016) were analyzed.The same surgical method was performed with piggyback liver transplantation.Observation indicators contained (1) recipient postoperative liver function;(2) the postoperative complications;(3) the recipient survival rate.SPSS 19.0 statistical software was used for analysis.Results (1) The curative effect was evaluated by the changes of ALT and TBIL among three groups of recipients postoperatively.As compared with C-Ⅰ transplantation group and CⅢ transplantation group,the level of ALT in C-Ⅱ transplantation group was significantly increased (P ＜0.05),the clinical efficacy was poorer.(2) The incidence of PNF was 3.23％ in C-Ⅰ group,9.88％ in C-Ⅱ group and 9.88％ in C-Ⅲ group (P＜0.05).The incidence of acute rejection was respectively 9.68％ in C-Ⅰ group,38.27％ in C-Ⅱ group and 38.27％ in C-Ⅲ group (P＜0.001).The incidence of SIRS was respectively 5.65％ in C-Ⅰ group,39.50％ in C-Ⅱ group and 39.50％ in C-Ⅲ group (P＜ 0.001).There were significant differences in the incidence of other complications among the three groups.(3) There were 14 deaths within 3 months,accounting for 17.28％,and the survival rate was 82.72％ in C-Ⅱ group,the 1-,3-,and 5-year survival rate was 76.55％,74.18％ and 76.55％ respectively in C-Ⅰ group,and that was 88.02％,85.72％ and 81.11％ respectively in C-Ⅲ group.Conclusion Since June 2015,C-Ⅰ donors grow up more quickly on year-on-year basis than C-Ⅱ.Simultaneously,the sort-term and long-term clinical efficacy is better in C-Ⅰ transplantation group than in C-Ⅱ transplantation group.How to repair the three types of Chinese standard donor organs and optimize the quality is still a hot point to ensure the healthy development of organ transplantation in China,which needs further investigation.
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Objective To sum up the experiences in liver transplantations from donation after brain death (DBD),and compare the clinical effect,complications and influential factors with international situation.Methods The retrospective descriptive study was adopted.All the data of 66 DBD liver donors and the matched recipients from authors' affiliations during June 2010 and June 2013 were collected.Original articles,meta-analysis and data reports with high academic influence were read and data were analyzed with SPSS 22.0.Results The incidence of serious complications,vascular complications and biliary complications during the first year among 66 recipients was 21.2％,10.6％,and 6.1％,respectively.Compared to international situation,graft 1-,3-,and 5-year survival rate was similar (P＞0.05) (83％,80％ and 73％ respectively),similar to that of recipients.There was no statistically significant difference in primary nonfunction and vascular complications between our center and other centers.As for biliary complications,morbidity was lower in our center (P＜0.05).The 3-and 5-year survival rate of recipients was also similar (P＞0.05),though the 1-year survival rate was slightly lower (P＜ 0.05).Conclusion These findings provide evidence that patient's prognosis under DBD liver transplantation in our center is acceptable,and long-term survival rate has reached international level.Still,1-year survival rate of recipients is unsatisfactory.In order to achieve a good clinical efficacy,we need to find out disadvantages during donor maintenance,recipient selection,surgical procedure and postoperative management.
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International norms of organ transplantation mainly depends on the organ donation after the death of citizens. Numbers of studies on the quality of donated livers were conducted to reduce the early postoperative primary dysfunctions and relevant complications. The donations is based on donation after brain death (DBD) and donation after cardiac death (DCD). Hence, the differences in the quality of liver from DBD and DCD are the focus.
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Humans , Brain Death , Liver , Physiology , Liver Transplantation , Tissue Donors , Tissue and Organ ProcurementABSTRACT
Recent years, the researchers have found a new type of cell death, referred to programmed necrosis or necroptosis, which involves the death receptor and the ligand binds and is initiated under the inhibition of apoptosis pathway. Programmed necrosis possesses the morphological features of typical necrosis accompanied by inflammation. The receptor interacting protein kinase 1/3(RIPK1/3) can be inhibited by the specific inhibitors, such as necrostatin-1. RIPK1/3 could regulate programmed necrosis and play a key role in the process. The significance of programmed necrosis in ischemia-reperfusion injury (IRI) has been attracted great attention at present. Simultaneously, a series of studies have found it also involves in the IRI of heart, kidney, brain and retina.
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Humans , Apoptosis , Imidazoles , Indoles , Inflammation , Necrosis , Receptor-Interacting Protein Serine-Threonine Kinases , Reperfusion InjuryABSTRACT
Auto liver transplantation (ALT) is a treatment option for patients with liver space-occupying lesion that could not be removed by conventional surgery and severe liver trauma,which also helps alleviate the shortage of donor liver.But many problems like the preoperative assessment,the tolerance of patients to surgery and anesthesia,delayed postoperative recovery of the liver function,primary non-function,liver failure and hepatic encephalopathy and even death still need to be addressed.Thus,it is particularly important to evaluate the operative indication,completely and accurately assess the preoperative liver function and liver function reserve,and reduce the perioperative mortality and complication in order to improve the prognosis of ALT.Combined with literalure and the experience in our center,this paper summarized the research advance of preoperative assessment in patients with ALT.
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Objective To investigate the extraction and purification methods of serum specific endothelial cell antibody of renal transplant recipients with rejection after renal transplantation.Methods Human umbilical vein endothelial cell (HUVEC)was isolated and cultured.The serum samples of the renal transplant recipients with poor renal function after renal transplantation were collected.Specific endothelial cell antibody was screened out with flow cytometry;antibodies against human leukocyte antigen (HLA)and major histocompatibility complex class Ⅰ-related chain A (MICA)were detected by Luminex platform.After the existence of specific endothelial cell antibody in the serum sample was confirmed,specific endothelial cell antibody was absorbed with HUVEC.The cell was washed and then the absorbed antibody was eluted from the cell membrane.Antibody IgG in the eluent was purified and concentrated again with Protein-A /G magnetic beads.Antibody activity in the eluent was detected by flow cytometry and the purified specific endothelial cell antibody (IgG)was identified by SDS-polyacrylamide gel (SDS-PAGE)and Western blot.Results In the serum of 386 renal transplant recipients,the serum samples of 5 renal transplant recipients with serum creatinine (Scr) >400 μmoI /L,negative anti-HLA antibody,negative anti-MICA antibody and median fluorescence intensity (MFI) >16 were selected.Purified specific endothelial cell antibody IgG showed immunoglobulin heavy chain (purity > 95%)by SDS-PAGE gel.Flow cytometry showed that the purified antibody had the feature of rebinding with the surface antigen of vascular endothelial cell.Conclusions The purification method of using human umbilical vein endothelial cell to absorb specific endothelial cell antibody in the serum of renal transplant recipients may obtain good effect.
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Auto liver transplantation (ALT) has been tremendously popular in hepatic surgery for the liver masses due to lack of enough donor for allogeneic transplantation of liver.But ALT remains stagnant because it is technically more difficult than liver transplantation.Much difficulties in this field lying ahead.Related surgical technical requirements for surgeons operating ALT,complications,difficult liver resection,hypothermic liver perfusion,veno-venous bypass,ex vivo ECMO perfusion and liver trim,assess the quality and volume of autoplast,autoplast implant and vascular anastomosis.On the other hand,the therapeutic effect largely depends on the intraoperative vascular separating range,the location and size of the tumor,the scope of lymphoid infiltrates by neoplast,the intubation site for perfusion and the sequence of opening the occlusion vessel.Thus,it's necessary to set up a scientific,normative ALT procedure to improve the therapeutic effect and prognosis.
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Organ transplantation is the effective method to replace the function of the patient failed organ. But it is very disappoint that recipients have to receive the long-term immunosuppression regimens for prevention of allograft rejection. To induce allograft immune tolerance without immunosuppressant is in great demand. Although several tolerance strategies for organ transplant have been proposed, even some has already been tested in the 1st clinical trial, these strategies haven ' t approached to ideal efficacy. Helminths are remarkably successful parasites to achieve immunological tolerance to host immune response. It is now well established that the parasites′ success is the result of active immunomodulation of their hosts ' immune response. We suggest that injecting B cells from donor spleen and helminth soluble antigens, recipient might become tolerance to donor organ, but not tolerated to other antigens. Research based on this approach has great translated value for future clinic practice.
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Objective To investigate modified technique of renal transplantation model in rats.Methods Sprague-Dawley rats were selected as donors ( n=21 ) and Wistar rats as recipients ( n=42 ) .Renal allografts of both sides were harvested from the donors for renal transplantation.After resection of left kidney , end-to-end anastomosis of renal arteries between donor and recipient was performed by the assistance of home-made catheter.And end-to-end anastomosis between recipient's renal vein and donor's inferior vena cava was also performed.The donor's ureter with bladder patch was anastomosed to the recipient's bladder.Finally the right kidney was removed , cefminox (10 mg) was injected intraperitoneally , and then the abdominal cavity was closed.The operation data were recorded , including the operation time , artery and vein anastomosis time , cold and warm ischemia time and so on.Living for 3 days after operation was regarded as a success model.The success rate of modeling was calculated and the cause of death was analyzed.Results The operation time of donor was (32.7 ±5.6) min, and repair time for kidney was (4.2 ±1.1) min.The operation time of recipient was (42.3 ±42.3) min, including (10.1 ±3.2) min of the artery anastomosis time , (13.9 ±2.5) min of vein anastomosis time, (6.3 ±1.4) min of urinary tract reconstruction time.Warm ischemia time was (5.4 ± 1.8) s, and cold ischemia time was (56.2 ±7.3) min.In 42 recipient rats, 40 rats were successful modeling and the success rate was 95.2%.Two rats died.One died of artery anastomosis hemorrhage , and the other died of diffuse peritonitis caused by urine leakage.Conclusions Renal transplantation model in rats with modified vascular end-to-end anastomosis has the characters of simple handling , short operation time and high success rate.
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<p><b>BACKGROUND</b>Our goal was to evaluate the outcomes of kidney transplants from controlled cardiac death donors compared with brain death donors by conducting a meta-analysis of cohort studies.</p><p><b>METHODS</b>The PubMed database and EMBASE were searched from January 1980 to July 2013 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, and outcome assessments.</p><p><b>RESULTS</b>Nine cohort studies involving 84 398 participants were included in this meta-analysis; 3 014 received kidneys from controlled cardiac death donors and 80 684 from brain death donors. Warm ischemia time was significantly longer for the controlled cardiac death donor group. The incidence of delayed graft function was 2.74 times (P < 0.001) greater in the controlled cardiac death donor group. The results are in favor of the brain death donor group on short-term patient and graft survival while this difference became nonsignificant at mid-term and long term. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.</p><p><b>CONCLUSION</b>This meta-analysis of retrospective cohort studies suggests that the outcome after controlled cardiac death donors is comparable with that obtained using kidneys from brain death donors.</p>