FUT1-mediated terminal fucosylation acts as a new target to attenuate renal fibrosis.

BACKGROUNDS: Renal fibrosis is a common pathologic process of most chronic kidney diseases (CKDs), becoming one of the major public health problems worldwide. Terminal fucosylation plays an important role in physiological homeostasis and pathological development. The present study aimed to explore the role of terminal fucosylation during kidney fibrogenesis and propose a possible anti-fibrosis treatment via suppressing aberrant terminal fucosylation. METHODS: We investigated the expression level of fucosyltransferase1 (FUT1) in CKD patients by using public database. Then, we further confirmed the level of terminal fucosylation by UEA-I staining and FUT1 expression in unilateral ureteral obstruction (UUO)-induced renal fibrosis mice. Immunostaining, qPCR, western blotting and wound healing assay were applied to reveal the effect of FUT1 overexpression in human kidney proximal tubular epithelial cell (HK-2). What's more, we applied terminal fucosylation inhibitor, 2-Deoxy-D-galactose (2-D-gal), to determine whether suppressing terminal fucosylation ameliorates renal fibrosis progression in vitro and in vivo. RESULTS: Here, we found that the expression of FUT1 significantly increased during renal fibrosis. In vitro experiments showed upregulation of epithelial-mesenchymal transition (EMT) after over-expression of FUT1 in HK-2. Furthermore, in vivo and in vitro experiments indicated that suppression of terminal fucosylation, especially on TGF-ßR I and II, could alleviate fibrogenesis via inhibiting transforming growth factor-ß (TGF-ß)/Smad signaling. CONCLUSIONS: The development of kidney fibrosis is attributed to FUT1-mediated terminal fucosylation, shedding light on the inhibition of terminal fucosylation as a potential therapeutic treatment against renal fibrosis.

2-D-gal Targets Terminal Fucosylation to Inhibit T-cell Response in a Mouse Skin Transplant Model.

BACKGROUND: Organ allograft rejection is mainly driven by T-cell response. Studies have shown that fucosylation plays essential roles in the immune cell development and function. Terminal fucosylation inhibitor, 2-deoxy-D-galactose (2-D-gal), has been reported to suppress immunoresponse of macrophages, but its effects on T-cell-mediated immune response and transplant rejection have not been fully explored. METHODS: The terminal fucosylation level in T cells was detected through ulex europaeus agglutinin-I staining. The consequences of 2-D-gal on murine T-cell proliferation, activation, cytokine secretion, and cell cycle were investigated in vitro. T-cell receptor signaling cascades were examined. Last, mouse skin transplant model was utilized to evaluate the regulatory effects of 2-D-gal on T-cell response in vivo. RESULTS: The expression of fucosyltransferase1 was upregulated in CD3/CD28-activated T cells along with an elevation of α(1,2)-fucosylation level as seen by ulex europaeus agglutinin-I staining. Furthermore, 2-D-gal suppressed T-cell activation and proliferation, decrease cytokines production, arrest cell cycle, and prevent the activation of T-cell receptor signaling cascades. In vivo experiments showed that 2-D-gal limited T-cell proliferation to prolong skin allograft in mice. This was accompanied by lower level of inflammatory cytokines, and were comparable to those treated with Cyclosporin A. CONCLUSIONS: Terminal fucosylation appears to play a role in T-cell activation and proliferation, and its inhibitor, 2-D-gal, can suppress T-cell activation and proliferation both in vitro and in vivo. In a therapeutic context, inhibiting terminal fucosylation may be a potential strategy to prevent allogeneic transplant rejection.

Pre-transplant infusion of donor leukocytes treated with extracorporeal photochemotherapy induces immune hypo-responsiveness and long-term allograft survival in murine models.

Recipients of solid organ transplantation (SOT) rely on life-long immunosuppression (IS), which is associated with significant side effects. Extracorporeal photochemotherapy (ECP) is a safe, existing cellular therapy used to treat transplant rejection by modulating the recipient's own blood cells. We sought to induce donor-specific hypo-responsiveness of SOT recipients by infusing ECP-treated donor leukocytes prior to transplant. To this end, we utilized major histocompatibility complex mismatched rodent models of allogeneic cardiac, liver, and kidney transplantation to test this novel strategy. Leukocytes isolated from donor-matched spleens for ECP treatment (ECP-DL) were infused into transplant recipients seven days prior to SOT. Pre-transplant infusion of ECP-DL without additional IS was associated with prolonged graft survival in all models. This innovative approach promoted the production of tolerogenic dendritic cells and regulatory T-cells with subsequent inhibition of T-cell priming and differentiation, along with a significant reduction of donor-specific T-cells in the spleen and grafts of treated animals. This new application of donor-type ECP-treated leukocytes provides insight into the mechanisms behind ECP-induced immunoregulation and holds significant promise in the prevention of graft rejection and reduction in need of global immune suppressive therapy in patients following SOT.

Modulation of Donor-Specific Antibody Production After Organ Transplantation by Valproic Acid: A Histone Deacetylase Inhibitor.

BACKGROUND: Antibody-mediated rejection, mediated by donor-specific antibodies, is emerging as a leading cause for allograft dysfunction in organ transplantation. Histone deacetylase inhibitors (HDACi) have potential immunosuppressive action, but their effects on antibody-mediated rejection and B cell function in organ transplantation have not been fully explored. METHODS: The impacts of valproic acid (VPA), an HDACi, on isolated murine B cell proliferation, apoptosis, class switch recombination (CSR), differentiation, and secretion of immunoglobulin were investigated in vitro and in vivo. Molecular mechanisms were also explored by analyzing the expression of the activation-induced cytidinedeaminase, B lymphocyte-induced maturation protein-1 (Blimp-1/Pridm1), X-box-binding protein 1 and interferon-regulatory factor 4. Mouse cardiac transplant model was used to evaluate the regulatory effects of VPA on B cell response in vivo. RESULTS: Valproic acid significantly inhibited B cell CSR, plasma cell differentiation, thereby reduced antibody generation in a dose-dependent manner without altering B cell proliferation and apoptosis in vitro and in vivo. Activation-induced cytidinedeaminase, Blimp-1/Pridm1 and X-box-binding protein 1 expression were repressed by VPA treatment in a dose-dependent manner, whereas no obvious changes were observed on interferon-regulatory factor 4 expression. Although VPA alone did not prolong the graft medium survival time after murine heart transplantation, the low levels of donor-specific antibody, especially IgG in serum and the less numbers of plasma cells in the spleen were observed in VPA-treated mice. CONCLUSIONS: Valproic acid inhibited B cell CSR and plasma cell differentiation in vitro and in nitrophenyl-chicken gamma globulin-immunized and heart transplant recipient mice. HDACi might be a therapeutic agent targeting B cell response after organ transplantation.

[The correlation between platelet parameters and acute rejection after renal transplantation].

OBJECTIVE: To investigate the relationship between acute graft rejection early after renal transplantation and the variations of platelet parameters. METHODS: We retrospectively analyzed the clinical data of 167 renal transplant recipients before and within 2 months after the surgery. Before and at 1-10 days, 15 days, 30 days, 45 days and 60 days after the transplantation, 5 platelet parameters, including platelet count (PLT), platelet hematocrit (PCT), mean platelet volume (MPV), platelet volume distribution width (PDW), and large platelet ratio (P-LCR), were detected in the 35 patients with acute graft rejection within two months (AR group) and in the other 132 recipients with good graft recovery (control group). RESULTS: The AR group and control group showed no significant difference in PLT, PCT, MPV, or P-LCR before the surgery, but the PDW was significantly higher in the AR group (t=2.18, P=0.035). These parameters were similar within 5 postoperative days between the two groups (P>0.05), but in postoperative days 6-15, the AR group showed significantly increased MPV, PDW and P-LCR compared with the control group (P<0.05). In postoperative days 6-9, MPV, PDW and P-LCR became stable in AR group but tended to decrease in the control group, showing obviously different patterns of variation between the two groups (P<0.05). CONCLUSIONS: Preoperative PDW may have a positive correlation with acute graft rejection after renal transplantation. Monitoring the variations of MPV, PDW and P-LCR may help in the diagnosis of acute graft rejection early after renal transplantation.

Impaired selectin-dependent leukocyte recruitment induces T-cell exhaustion and prevents chronic allograft vasculopathy and rejection.

Selectin-selectin ligand interactions mediate the initial steps in leukocyte migration, an integral part of immune responses. Fucosyltransferase-VII (FucT-VII), encoded by Fut7, is essential for biosynthesis of selectin ligands. In an established model of cardiac allograft vasculopathy and chronic rejection, Fut7(-/-) recipients exhibited long-term graft survival with minimal vasculopathy compared with WT controls. Graft survival was associated with CD4 T-cell exhaustion in the periphery, characterized by impaired effector cytokine production, defective proliferation, increased expression of inhibitory receptors programmed death-1 (PD-1) and T cell Ig- and mucin-domain-containing molecule-3 (Tim-3), low levels of IL-7Rα on CD4 T cells, and reduced migration of polyfunctional CD4 memory T cells to the allograft. Blocking PD-1 triggered rejection only in Fut7(-/-) recipients, whereas depleting regulatory T cells had no effect in either Fut7(-/-) or WT recipients. Adoptive transfer experiments confirmed that this CD4 T cell-exhausted phenotype is seen primarily in Fut7(-/-) CD4 T cells. These data suggest that impaired leukocyte recruitment is a novel mechanism leading to CD4 T-cell exhaustion. Our experimental system serves as an excellent model to study CD4 T-cell exhaustion as a dominant mechanism of transplant tolerance. Further, targeting FucT-VII may serve as a promising strategy to prevent chronic allograft rejection and promote tolerance.

Effects of post-discharge nurse-led telephone supportive care for patients with chronic kidney disease undergoing peritoneal dialysis in China: a randomized controlled trial.

BACKGROUND: Patients with end-stage renal failure (ESRF) need integrated health care to maintain a desirable quality of life. Studies suggest that post-discharge nurseled telephone support has a positive effect for patients suffering from chronic diseases. But the post-discharge care is under-developed in mainland China and the effects of post-discharge care on patients with peritoneal dialysis have not been conclusive. AIM: The purpose of this study is to test the effectiveness of postdischarge nurse-led telephone support on patients with peritoneal dialysis in mainland China. METHODS: A randomized controlled trial was conducted in the medical department of a regional hospital in Guangzhou. 135 patients were recruited, 69 in the study group and 66 in the control group. The control group received routine hospital discharge care. The study group received post-discharge nurse-led telephone support. The quality of life (Kidney Disease Quality of Life Short Form, KDQOL-SF), blood chemistry, complication control, readmission and clinic visit rates were observed at three time intervals: baseline before discharge (T1), 6 (T2) and 12 (T3) weeks after discharge. RESULTS: Statistically significant effects were found for symptom/problem, work status, staff encouragement, patient satisfaction and energy/fatigue in KDQOL-SF and 84-day (12-week) clinic visit rates between the two groups. The study group had more significant improvement than the control group for sleep, staff encouragement at both T2 and T3, and pain at T2 and patient satisfaction at T3. No significant differences were observed between the two groups for the baseline measures, other dimensions in KDQOL-SF, blood chemistry, complication control, readmission rates at all time intervals and clinic visit rates at the first two time intervals. CONCLUSIONS: Post-discharge nurse-led telephone support for patients undergoing peritoneal dialysis is effective to enhance patients' well-being in the transition from hospital to home in mainland China.

USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation.

The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell-cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell-cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.

[Trichostatin A inhibits the activation of CD(4)(+) T cells by suppressing CD(28) expression in mice].

OBJECTIVE: To investigate the mechanism of trichostatin A(TSA), a histone deacetylase (HDAC) inhibitor, in inhibiting the activation of CD(4)(+) T cells in mice. METHODS: The CD(4)(+) T cells isolated from the spleen of C57BL mice were treated with different concentrations of TSA (2, 20, and 200 nmol/L) for 24 h, and CD(3), CD(28) and interleukin-2 (IL-2) mRNA levels were measured with reverse transcription-polymerase chain reaction. The protein expressions of CD(3), CD(28) and IL-2 were measured by fluorescence-activated cell sorting and ELISA analysis. ZAP70 and PI3K protein expression in CD(4)(+) T cells activated by CD(3) and CD(28) monoclonal antibody were analyzed by Western blotting. RESULTS: TSA dose-dependently inhibited the transcription and protein expression of CD28 in CD(4)(+) T cells and reduced the expression of PI3K protein in activated CD(4)(+) T cells, without showing significant effect on the expression of ZAP70. TSA treatment of the cells also resulted in significantly decreased mRNA and protein expressions of IL-2 (P<0.01). CONCLUSION: TSA can regulate the immunological activity of CD(4)(+) T cells by inducing mRNA and protein expressions of CD(28), which inhibits the activation of the co-stimulatory signal transduction in CD(4)(+) T cells and decreases the secretion of IL-2.

[Long-term survival of high-risk kidney transplant patients].

OBJECTIVE: To summarize the experiences in high-risk renal transplant recipients for ketter long-term survival. METHODS: From April 1991 to December 2008, a total of 921 kidney recipients with high-risk factors were divided into six groups as following: (1) pediatric patients (< 18 years old) (GI, n = 34); (2) retransplant recipients (GII, n = 169); (3) high sensitized patients (PRA> 30% or peak PRA > 50%)(GIII, n = 35); (4) elderly recipients (> 60 years old) (GIV, n = 297); (5) diabetic patients (GV, n = 112); (6) patients with HBV/HCV infection or HBV/HCV carrier (GVI, n = 274). Each group was compared to a control of 807 recipients without any above risk factor for patient and graft survival at 1, 3 and 5 years. Incidences of acute rejection (AR), chronic rejection (CR) and complication were analyzed and compared respectively between the studied subjects and the control group as well. RESULTS: Compared with the control group, patient/graft survivals were lower in GII, GIII and GVI (all P < 0.05), GIV had worse patient survival (P < 0.05); AR and CR incidences were greater in GI and GIII (all P < 0.05); GIV, GV and GVI had more complications. CONCLUSIONS: This study suggests the benefits for long-term outcome in high-immunological risk renal transplant recipients of low acute selection incidence rate, and reduction of complication incidences is the key to long term results for non-immunological high risk recipients.

L-carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway.

Oxidative stress has been considered as the possible mechanism of renal ischemia/reperfusion injury. L-carnitine is an endogenous mitochondrial membrane compound and could effectively protect ischemia-reperfusion injury in the kidney. To elucidate the nephroprotective effects of L-carnitine, here we assessed the effect of L-carnitine on hydrogen peroxide (H(2)O(2))-mediated oxidative stress in the human proximal tubule epithelial cell line, HK-2 cells. The results showed that pretreatment with L-carnitine 12h inhibited H(2)O(2)-induced cell viability loss, intracellular reactive oxygen species generation and lipid peroxidation in a concentration-dependent manner. Also L-carnitine promoted endogenous antioxidant defense components including total antioxidative capacity, glutathione peroxidase, catalase and superoxide dismutase. In parallel, cell apoptosis triggered by H(2)O(2) characterized with the DNA fragment and caspase-3 activity were also inhibited by L-carnitine. Furthermore, mitochondrial dysfunction associated with cell apoptosis including membrane potential loss, down-regulation of Bcl-2 and up-regulation of Bax and the release of cytochrome c were abrogated in the presence of L-carnitine. These results suggested that L-carnitine could protect HK-2 cells from H(2)O(2)-induced injury through the inhibition of oxidative damage, mitochondria dysfunction and ultimately inhibition of cell apoptosis, which indicates that L-carnitine may be a promising approach for the treatment of oxidative stress in renal diseases.

[Multivariate analysis of the risk factors of cytomegalovirus pneumonia after renal transplantation].

OBJECTIVE: To identify the risk factors for cytomegalovirus (CMV) pneumonia after renal transplantation and investigate the early precaution measures. METHODS: A retrospective study was conducted in a group of 28 patients undergoing renal transplantation who were readmitted because of CMV pneumonia between Jan, 2005 and Dec, 2007. Chi-square test and multivariate logistic regression were used to identity the significant risk factors. RESULTS: Seven factors, namely recipient age, acute graft rejection, pre-transplantation dialysis, delayed graft function recovery, recipient peak PRA level, donor CMV positivity and the use of MMF were found to significantly correlate to post-transplant CMV pneumonia. Multivariate logistic regression further confirmed that donor CMV IgG positivity, acute graft rejection and pre-transplantation dialysis for over 6 months were independent factors to predict the occurrence of CMV pneumonia. CONCLUSIONS: Acute graft rejection control, appropriate donor selection and shortened dialysis before the transplantation can be crucial factors to reduce the incidence of CMV pneumonia after renal transplantation.

[Clinical study of pulmonary infection in kidney transplantation recipients taking new immunosuppressant].

OBJECTIVE: To explore the etiopathogenesis, therapy and incidence of pulmonary infection in kidney transplantation recipients taking new immunosuppressant. METHODS: The clinical data from 752 kidney transplant recipients were retrospectively analyzed, who were divided into 3 groups according to the immunosuppressants administered, namely group A (CsA+MMF+Pred, n=226), group B (FK506+MMF+Pred, n=386) and group C (FK506+Rap+Pred, n=140). The incidence and mortality of pulmonary infection were recorded and the analysis of etiopathogenesis, diagnosis and therapy of pulmonary infection were carried out in the 3 groups. RESULTS: Fifty-three patients acquired post-transplant pulmonary infection. The incidence of pulmonary infection was 7.08% (16/226) in group A, 7.25% (28/386) in group B and 6.43% (9/140) in group C. One patient died in group A and 2 in group B. Among the 53 patients, 24 had simple bacterial infection, 9 had cytomegalovirus infection, 1 had mycotic infection, 17 had combined infection, and 2 had unidentified pathogen infection. Of the pathogenic bacteria detected, 68.35% were Gram-negative. CONCLUSION: Gram-negative bacteria are most likely responsible for pulmonary infection after kidney transplantation, which most possibly occurs within 6 months after kidney transplantation. Early diagnosis and early treatment are critical for decreasing the mortality of severe pneumonia and for improving the survival rate of the patients and grafts.

[Effect of trichostatin A on proliferation and interleukin-2 expression of mouse T cells in mixed lymphocyte culture].

OBJECTIVE: To investigate the effect of trichostatin A (TSA) on proliferation and interleukin-2 (IL-2) expression of mouse T cells in mixed lymphocyte culture (MLC), and explore its effect on T cell-mediated immune response. METHODS: BALB/c and C57BL mouse MLC was treated with different concentrations of TSA for different durations, and the lymphocyte inhibition ratio was measured by MTT assay. With CTX as the control, one-way MLC system of BALB/c and C57BL mouse was treated with the same concentrations of TSA, and IL-2 expression in the T cells was observed by flow cytometry. RESULTS: TSA inhibited the proliferation of T cells in the MLC in a time- and dose-dependent fashion. It also reduced the IL-2 expression in one-way MLC dose-dependently, showing it significantly differed from the effect of CTX (P<0.01). CONCLUSION: Histone deacetylase inhibitor TSA can inhibit the proliferation and reduce IL-2 expression of the T cells in MLC of mice, and therefore inhibit the T cell-mediated immune response.

[Application of mycophenolate mofetil in hepatitis C patients after kidney transplantation].

OBJECTIVE: To discuss adequate application of mycophenolate mofetil (MMF) in hepatitis C patients after kidney transplantation. METHOD: A one-year follow-up study was conducted in 49 patients with hepatitis C but normal liver function before kidney transplantation, who were given postoperatively immunosuppressants of predisone, MMF and CsA/FK506. Patients with abnormal liver function after kidney transplantation who continued MMF therapy at routine dose and those with reduced or suspended MMF therapy all received intravenous therapy for liver protection, and the duration of therapies was recorded. RESULTS: Nineteen patients presented with abnormal liver function after operation, and the duration of abnormal liver function till recovery was 32.82-/+4.13 days in the patients with unsuspended MMF therapy and 13.31-/+2.98 days in those with reduced or suspended MMF (P<0.05); the former patients required subsequently 62.7-/+3.23 days to recover normal liver function and the latter need only 23.4-/+2.29 days (P<0.05). CONCLUSION: MMF should be reduced or suspended when liver function abnormality occurred in patients with hepatitis C after kidney transplantation, and immediate intravenous therapy for liver protection may prove beneficial.

[Clinical observation on long-term surviving patients after combined abdominal organ transplantation].

OBJECTIVE: To summarize the treatment experience of long-term surviving patients after combined abdominal organ transplantation. METHODS: From October 2001 to January 2005, 19 patients received combined abdominal organ transplantation in Nanfang Hospital, including 6 with simultaneous kidney-pancreas transplantation (SKPT), 12 with combined liver-kidney transplantation (CLKT), and 1 with simultaneous liver-pancreas transplantation (SLPT). The periods of follow up were from 6 months to 3 years and 8 months. Summarize primary diseases of the patients, factors which impacted on patients long-term survival rate, and immunological characteristics of combined abdominal organ transplantation. RESULTS: All of 19 transplant cases were performed successfully. Among then, 18 were followed up; 16 survived till now; 2 patients undergoing liver-kidney transplantation were dead, one of which died from myocardial infarction in the 18 months after operation, and one died from cytomegalovirus in infection of lung in 13 months; 1 liver-kidney transplantation patient and 2 pancreas-liver transplantation patients experienced acute rejection once; 2 patients were found nephrotoxicity. Among the 18 patients, 4 patients' survival time were over 3 years, 7 over 2 years, 6 over 1 year, 1 over 10 months. CONCLUSIONS: Combined abdominal organ transplantation is effective for treatment of two abdominal organ failure diseases. Factors which impact on patients long-term surviving include choosing suitable recipient, high quality of donated organ, avoidance of surgical complication, the history of myocardial infarction before operation, immunosuppressive regime and virus infection late after transplantation. Combined abdominal organ transplantation has some different immunological characteristics from single organ transplantation.

[Simultaneous liver-pancreas-duodenum transplantation: one case report and review of the literature].

OBJECTIVE: To investigate the effect of treatment on end-stage liver disease and type-I diabetes mellitus with simultaneous liver-pancreas-duodenum transplantation. METHOD: In September 2003, one patient with chronic hepatitis B, liver cirrhosis, hepatic cellular cancer, and insulin-dependent diabetes received simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantation. Liver and pancreas graft function was monitored after transplantation. RESULTS: The function of pancreas allograft was recovered immediately and the patient became insulin-independence postoperatively. The liver allograft was experienced an acute rejection episode and reversed by intravenous bolus methylprednisolone. The recipient was currently liver disease-free and insulin-free more than 21 months. CONCLUSIONS: The simultaneous liver-pancreas-duodenum transplantation is an effective method in the treatment of end-stage liver disease and type-I diabetes mellitus.

[Perioperative management of multiorgan transplantation].

OBJECTIVE: To summarize the experience with perioperative management of multiorgan transplantation. METHODS: From October 2001 to January 2005, 19 patients received multiorgan transplantation in Nanfang Hospital, including 6 with simultaneous kidney-pancreas transplantation (SKPT), 12 with combined liver-kidney transplantation (CLKT), and 1 with simultaneous liver-pancreas transplantation (SLPT). The surgical techniques, application of immunosuppressants, and complication management were reviewed. RESULTS: All transplantation procedures were performed successfully. The transplantation-related complications included tacrolimus-induced renal toxicosis in 1 (5.3%) case, acute graft rejection in 3 (15.8%) cases, intestinal hemorrhage in 2 (10.5%) cases, intra-abdominal hemorrhage in 1 (5.3%) case, and lung infection in 1 (5.3%) case, all of which were cured after proper treatment. CONCLUSIONS: Donor selection, good quality of the donor organ, proper surgical approaches, adequate use of the-mmunosuppressants, and prevention of complications are essential to the success of multiorgan transplantation.

[Simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantation in a diabetic patient with end-stage liver disease].

OBJECTIVE: To study the effect of combined transplantation of the liver and the pancreas in diabetic patients with end-stage liver disease, and explore the optimal surgical procedure. METHODS: Simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantations were performed in a patient diagnosed as having chronic hepatitis B, hepatocirrhosis, hepatic cellular cancer, and insulin-dependent diabetes. Immunosuppression therapy utilized prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and simulect. The function of the liver graft, serum amylase and lipase, blood glucose, and C-peptide were monitored after transplantation. RESULTS: Insulin was withdrawn at the 6th day after operation, good liver allograft functional recovery was achieved, without such complications as pancreatitis, thrombosis, and localized infections. CONCLUSION: End-stage liver disease with concomitant insulin-dependent diabetes is the indication for combined liver-pancreas transplantations, for which simultaneous orthotopic liver and heterotopic pancreas-duodenum transplantations may constitute the optimal surgical approaches as the primary choice.