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Liver Grafts (liver + graft)
Kinds of Liver Grafts Terms modified by Liver Grafts Selected AbstractsUnique Early Gene Expression Patterns in Human Adult-to-Adult Living Donor Liver Grafts Compared to Deceased Donor GraftsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009J. De Jonge Because of inherent differences between deceased donor (DD) and living donor (LD) liver grafts, we hypothesize that the molecular signatures will be unique, correlating with specific biologic pathways and clinical patterns. Microarray profiles of 63 biopsies in 13 DD and 8 LD liver grafts done at serial time points (procurement, backbench and postreperfusion) were compared between groups using class comparisons, network and biological function analyses. Specific genes were validated by quantitative PCR and immunopathology. Clinical findings were also compared. Following reperfusion, 579 genes in DD grafts and 1324 genes in LDs were differentially expressed (p < 0.005). Many upregulated LD genes were related to regeneration, biosynthesis and cell cycle, and a large number of downregulated genes were linked to hepatic metabolism and energy pathways correlating with posttransplant clinical laboratory findings. There was significant upregulation of inflammatory/immune genes in both DD and LD, each with a distinct pattern. Gene expression patterns of select genes associated with inflammation and regeneration in LD and DD grafts correlated with protein expression. Unique patterns of early gene expression are seen in LD and DD liver grafts, correlating with protein expression and clinical results, demonstrating distinct inflammatory profiles and significant downregulation of metabolic pathways in LD grafts. [source] Significance of CT Attenuation Value in Liver Grafts Following Right Lobe Living-Donor Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2005Taku Iida In adult living-donor liver transplantation (LDLT), the assessment of the allograft functional reserve is important for adequate graft regeneration. From March 2002 to December 2003, 30 adult recipients underwent right lobe LDLT. Mean CT attenuation values (CT-AVs) in the graft were measured on unenhanced CT for 6 months after LDLT. The histological features of the graft parenchyma were evaluated with post-operative liver biopsy specimens. Mean CT-AVs after LDLT were decreased significantly from the pre-operative values, recovered to over 60 HU within 6 months. There was a positive linear correlation between the CT-AVs and the receptor index (LHL15) in technetium-99m-diethylenetriaminepenta-acetic acid-galactosyl-human serum albumin (99mTc-GSA) liver scintigraphy (r = 0.803, p = 0.005). The recipients were divided into two groups according to the CT-AV at one post-operative week (group H; ,55HU, group L; <55HU). The low CT-AVs, under 55 HU, in group L were prolonged for 3 months compared with those in group H (p < 0.05). The 1-year cumulative survival rate was 94.7% and 45.5% in groups H and L, respectively (p = 0.014). Histological findings revealed that the parenchymal damage was severe in the grafts with low CT-AVs. The CT-AVs in the grafts may be a useful parameter for assessing the allograft functional reserve. [source] Liver Transplantation Using Liver Grafts Preserved Under High PressureARTIFICIAL ORGANS, Issue 10 2005Takuya Ueno Abstract: To extend organ preservation time, we attempted to establish a unique method of maintaining a preservation solution in a stable unfrozen state below its freezing point by pressurizing the solution. Livers removed from Lewis rats (RT1l) were stored in UW solution pressurized at the prescribed pressure. After the termination of preservation, orthotopic liver transplantation was performed. Experiment 1: Liver grafts were pressurized up to 30, 40, 50, and 70 MPa and preserved at 0°C for 60 min. Experiment 2: Liver grafts were compressed at a rate of 1.32 or 0.04 MPa/s to 35 MPa and preserved for 60 min at 0°C. Experiments 3 and 4: Liver grafts were pressurized up to 5, 10, 20, and 30 MPa and preserved at ,2°C (Exp. 3), ,3°C or ,4°C (Exp. 4) for 5 h. All rats transplanted with livers pressurized up to 30 MPa (Exp. 1), all rats in the 5 MPa and control groups at ,2°C (Exp. 3), and all rats in the 5 MPa group at ,3°C (Exp. 4) survived for 2 weeks. In light microscopy, diffuse hemorrhage and vacuolar degeneration of hepatocytes were observed in a pressure-dependent manner. Liver grafts preserved under pressurized, subzero nonfrozen condition have sufficient function to sustain the life of rats after orthotopic transplantation. [source] Liver graft exposure to carbon monoxide during cold storage protects sinusoidal endothelial cells and ameliorates reperfusion injury in ratsLIVER TRANSPLANTATION, Issue 11 2009Atsushi Ikeda Hepatic ischemia/reperfusion (I/R) injury significantly influences short-term and long-term outcomes after liver transplantation (LTx). The critical step initiating the injury is known to include sinusoidal endothelial cell (SEC) alteration during the cold preservation period. As carbon monoxide (CO) has potent cytoprotective functions on vascular endothelial cells, this study examined if CO treatment of excised liver grafts during cold storage could protect SECs and ameliorate hepatic I/R injury. Rat liver grafts were preserved in University of Wisconsin (UW) solution containing 5% CO (CO-UW solution) for 18 to 24 hours and were transplanted into syngeneic Lewis rats. After 18 hours of cold preservation, SEC damage was evident with propidium iodide (PI) nuclear staining on SECs, and the frequency of PI+ SECs was significantly lower in grafts stored in CO-UW solution versus those stored in control UW solution. SEC protection with CO was associated with decreased intercellular cell adhesion molecule translocation and less matrix metalloproteinase release during cold preservation. After LTx with 18 hours of cold preservation, serum alanine aminotransferase levels and hepatic necrosis were significantly less in the CO-UW group than in the control UW group. With 24 hours of cold storage, 35% (7/20) survived with control UW solution, whereas the survival with CO-UW solution improved to 80% (8/10). These beneficial effects of CO-UW solution were associated with a significant reduction of neutrophil extravasation, down-regulation of hepatic messenger RNA for tumor necrosis factor alpha and intercellular cell adhesion molecule 1, and less hepatic extracellular signal-regulated kinase activation. Liver grafts from Kupffer cell,depleted donors or pseudogerm-free donors showed less SEC death during cold preservation, and CO-UW solution further reduced SEC death. In conclusion, CO delivery to excised liver grafts during cold preservation efficiently ameliorates SEC damage and hepatic I/R injury. Liver Transpl 15:1458,1468, 2009. © 2009 AASLD. [source] Liver grafts from donors with central nervous system tumors: A single-center perspectiveLIVER TRANSPLANTATION, Issue 10 2009Randeep Kashyap Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 ± 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 ± 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality. Liver Transpl 15:1204,1208, 2009. © 2009 AASLD. [source] Susceptibility of Liver Allografts to High or Low Concentrations of Preformed Antibodies as Measured by Flow CytometryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2001Juan C. Scornik Liver grafts are more resistant to damage by HLA antibodies than other organ allografts, but it is not clear if the antibodies are associated with graft rejection or graft loss, or if different antibody concentrations have different effects. To explore potential associations between antibody concentrations and outcome, preformed IgG antibodies against donor cells were quantified by flow cytometry in 465 consecutive liver transplant recipients. Antibody-positive patients were classified according to whether they had high or low antibody concentrations and analyzed for possible correlation with graft rejection or graft loss. The results showed that the incidence of rejection was not significantly different between antibody-positive and -negative patients. However, patients with high antibody concentrations had a higher incidence of steroid-resistant rejections (31% at 1 year) than patients with low antibody (4%) or no antibody (8%, p <,0.0004). These effects were mainly due to T-cell (HLA class I) antibodies. The overall incidence of rejection at 1 year was 69% for high antibody patients, 51% for patients with low antibodies and 53% for patients with no antibodies (p not significant). In an apparent paradox, antibody-positive patients underwent fewer early graft losses. Thus, the associations of preformed antibodies and outcome depend, on the one hand, on antibody concentrations, and on the other hand on whether the outcome measured is steroid-sensitive rejection, steroid-resistant rejection or graft survival. These complex interactions may explain the controversial results observed in previous studies. [source] Liver Transplantation Using Liver Grafts Preserved Under High PressureARTIFICIAL ORGANS, Issue 10 2005Takuya Ueno Abstract: To extend organ preservation time, we attempted to establish a unique method of maintaining a preservation solution in a stable unfrozen state below its freezing point by pressurizing the solution. Livers removed from Lewis rats (RT1l) were stored in UW solution pressurized at the prescribed pressure. After the termination of preservation, orthotopic liver transplantation was performed. Experiment 1: Liver grafts were pressurized up to 30, 40, 50, and 70 MPa and preserved at 0°C for 60 min. Experiment 2: Liver grafts were compressed at a rate of 1.32 or 0.04 MPa/s to 35 MPa and preserved for 60 min at 0°C. Experiments 3 and 4: Liver grafts were pressurized up to 5, 10, 20, and 30 MPa and preserved at ,2°C (Exp. 3), ,3°C or ,4°C (Exp. 4) for 5 h. All rats transplanted with livers pressurized up to 30 MPa (Exp. 1), all rats in the 5 MPa and control groups at ,2°C (Exp. 3), and all rats in the 5 MPa group at ,3°C (Exp. 4) survived for 2 weeks. In light microscopy, diffuse hemorrhage and vacuolar degeneration of hepatocytes were observed in a pressure-dependent manner. Liver grafts preserved under pressurized, subzero nonfrozen condition have sufficient function to sustain the life of rats after orthotopic transplantation. [source] Development of antibody to hepatitis B surface antigen after liver transplantation for chronic hepatitis BHEPATOLOGY, Issue 1 2003Chung-Mau Lo Patients with chronic hepatitis B virus (HBV) infection have a defective HBV-specific immune response, and the spontaneous development of antibody against hepatitis B surface antigen (anti-HBs) after liver transplantation has not been observed. We report the spontaneous production of anti-HBs in 21 of 50 (42%) patients receiving lamivudine monoprophylaxis after liver transplantation. Seroconversion to anti-HBs status (>10 mIU/mL) was found at a median of 8 days (range, 1 to 43 days) after transplantation. In each case, serial serum samples showed a >100% increase in antibody titer as compared with that of day 7 after transplantation in the absence of any blood product transfusion. The anti-HBs titer increased to a maximum within 3 months, and the peak titer was <100 mIU/mL in 10 patients, 100 to 1000 mIU/mL in 5 patients, and >1,000 mIU/mL in 6 patients. In 12 patients, anti-HBs disappeared from serum at a median of 201 days (range, 24 to 414 days), whereas the other 9 patients remained positive for anti-HBs at a median of 221 days (range, 94 to 1,025 days) after transplantation. Patients in whom anti-HBs in serum developed had a more rapid clearance of serum hepatitis B surface antigen (HBsAg) (log rank test, P = .011). Using logistic regression analysis, the only predictor of anti-HBs production was an HBV-immune donor (odds ratio, 18.9; 95% confidence interval, 3.2 to 112.4; P = .001). In conclusion, patients who undergo liver transplantation for chronic hepatitis B using lamivudine prophylaxis may develop anti-HBs spontaneously. The antibody is likely to be of donor origin, suggesting the possibility of adoptive immunity transfer through a liver graft. [source] Over-expression of Toll-like receptors and their ligands in small-for-size graftHEPATOLOGY RESEARCH, Issue 3 2010Weiwei Jiang Aim:, Toll-like receptors (TLRs) participate in several physiological and pathological processes of transplantation, including inflammation and allograft rejection, but the expression of TLRs and their ligands remains undetermined in small-for-size graft transplantation. Methods:, A non-arterialized partial liver transplantation model was used. The expression of TLR2 and TLR4 mRNA and protein, CD14 and Myeloid Differentiation-2 (MD-2) mRNA, as well as TLR2 and TLR4 exogenous ligands (endotoxin) and endogenous ligands [heat shock protein (HSP) 60 and 70] were assessed. The signaling pathways induced by TLR2 and TLR4 were also assessed. Results:, In small-for-size liver graft, the expression of mRNA and protein of TLR2 and TLR4, CD14 and MD-2 mRNA, as well as endogenous ligands of TLR2 and TLR4 such as HSP60 and HSP70 was quickly and significantly increased after reperfusion, and reached a peak at 3 h after reperfusion. The levels of exogenous ligands (endotoxin) were increased and reached a peak at 6 h after reperfusion. The appearance of TLR2 and TLR4 mRNA was accompanied by increased HSP 60 and 70 mRNA within 24 h after reperfusion. In the small-for-size group, the peak levels of TLRs and their endogenous ligands appeared earlier than those in the full size group; the peak levels of TLRs and their endogenous and exogenous ligands were higher than those in the full size group. Conclusion:,TLR2 and TLR4, as well as their endogenous and exogenous ligands were activated in small-for-size liver graft transplantation. [source] Ischaemic preconditioning of the graft in adult living related right lobe liver transplantation: impact on ischaemia,reperfusion injury and clinical relevanceHPB, Issue 7 2010Paola Andreani Abstract Background:, Ischaemic preconditioning (IPC) of the right liver graft in the donor has not been studied in adult-to-adult living related liver transplantation (LRLT). Objective:, To assess the IPC effect of the graft on ischaemia reperfusion injury in the recipient and compare recipient and donor outcomes with and without preconditioned grafts. Patients and methods:, Alternate patients were transplanted with right lobe grafts that were (n= 22; Group Precond) or were not (n= 22; Group Control) subjected to IPC in the living donor. Liver ischaemia,reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes were compared. Univariate and multivariate analyses were performed to identify factors predictive of the aspartate aminotransferase (AST) peak and minimum prothrombin time. Results:, Both groups had similar length of hospital stay, morbidity/mortality, primary non-function and acute rejection rates. Post-operative AST (P= 0.8) and alanine aminotransferase (ALT) peaks (P= 0.6) were similar in both groups (307 ± 189 and 437 ± 302 vs. 290 ± 146 and 496 ± 343, respectively). In univariate analysis, only pre-operative AST and warm ischemia time (WIT) were significantly associated with post-operative AST peak (in recipients). In multivariate analysis, the graft/recipient weight ratio (P= 0.003) and pre-operative bilirubin concentration (P= 0.004) were significantly predictive of minimum prothrombin time post-transplantation. Conclusions:, Graft IPC in the living related donor is not associated with any benefit for the recipient or the donor and its clinical value remains uncertain. [source] Single nucleotide insertion in the 5,-untranslated region of hepatitis C virus with clearance of the viral RNA in a liver transplant recipient during acute hepatitis B virus superinfectionLIVER INTERNATIONAL, Issue 1 2002Consolato Sergi Abstract: Hepatitis C virus (HCV) infection is an important etiology in patients undergoing orthotopic liver transplantation (OLT) world-wide. Antiviral therapy-related clearance of HCV RNA may occur both in patients with chronic HCV infection and in transplanted patients for HCV-related liver cirrhosis, but the role of the 5,-untranslated region (UTR) of HCV containing the internal ribosome entry site (IRES), which directs the translation of the viral open reading frame has not hitherto been evaluated. We studied the 5,-UTR in an HCV-infected recipient of a liver graft that showed spontaneous clearance of HCV RNA during an acute hepatitis B virus (HBV) superinfection. Sequencing of the 5,-UTR of HCV showed a nucleotide A insertion at position 193 of the IRES. [source] Adenosine restores the hepatic artery buffer response and improves survival in a porcine model of small-for-size syndrome,LIVER TRANSPLANTATION, Issue 11 2009Dympna M. Kelly The aim of the study is to define the role of the HABR in the pathophysiology of the SFS liver graft and to demonstrate that restoration of hepatic artery flow (HAF) has a significant impact on outcome and improves survival. Nine pigs received partial liver allografts of 60% liver volume, Group 1; 8 animals received 20% LV grafts, Group 2; 9 animals received 20% LV grafts with adenosine infusion, Group 3. HAF and portal vein flow (PVF) were recorded at 10 min, 60 min and 90 min post reperfusion, on POD 3 and POD 7 in Group 1, and daily in Group 2 and 3 up to POD 14. Baseline HAF and PVF (ml/100g/min) were 29 ± 12 (mean ± SD) and 74 ± 8 respectively, with 28% of total liver blood flow (TLBF) from the HA and 72% from the PV. PVF peaked at 10 mins in all groups, increasing by a factor of 3.8 in the 20% group compared to an increase of 1.9 in the 60% group. By POD 7-14 PVF rates approached baseline values in all groups. The HABR was intact immediately following reperfusion in all groups with a reciprocal decrease in HAF corresponding to the peak PVF at 10 min. However in the 20% group HAF decreased to 12 ± 8 ml/100 g/min at 90 min and remained low out to POD 7-14 despite restoration of normal PVF rates. Histopathology confirmed evidence of HA vasospasm and its consequences, cholestasis, centrilobular necrosis and biliary ischemia in Group 2. HA infusion of adenosine significantly improved HAF (p < .0001), reversed pathological changes and significantly improved survival (p = .05). An impaired HABR is important in the pathophysiology of the SFSS. Reversal of the vasospasm significantly improves outcome. Liver Transpl 15:1448,1457, 2009. © 2009 AASLD. [source] Gene expression profiling of acute cellular rejection in rat liver transplantation using DNA microarraysLIVER TRANSPLANTATION, Issue 5 2009Naoki Hama Acute cellular rejection (ACR) is still a major problem in organ transplantation, and its genetic and molecular mechanisms remain poorly understood. We used DNA microarrays to investigate the gene expression profiles in ACR. We hypothesized that changes of gene expression in grafts could also be detected in peripheral blood leukocytes. We first compared the gene expression profiles in liver isografts (Lewis to Lewis) and allografts (Dark Agouti to Lewis) harvested from rats at days 1, 3, 5, and 7 after transplantation. Hierarchical clustering analysis indicated that gene expression started to change on day 3, and 89 differentially expressed genes were extracted from allografts in comparison with isografts at day 3. Most of the up-regulated genes were associated with graft-infiltrating leukocytes. We then confirmed the similarity of gene expression changes in peripheral leukocytes by quantitative real-time polymerase chain reaction. We also investigated the gene expression changes in other inflammatory and liver dysfunction models. Two interferon-gamma inducible genes, interferon regulatory factor 1 and guanylate nucleotide binding protein 2, were overexpressed in both the peripheral leukocytes and liver graft during ACR. Although further studies are necessary, these 2 genes in peripheral leukocytes could be potentially useful markers for rejection or immunosuppression. Liver Transpl 15:509,521, 2009. © 2009 AASLD. [source] Does middle hepatic vein omission in a right split graft affect the outcome of liver transplantation?LIVER TRANSPLANTATION, Issue 6 2007A comparative study of right split livers with, without the middle hepatic vein Preservation of the middle hepatic vein (MHV) for a right split liver transplantation (SLT) in an adult recipient is still controversial. The aim of this study was to evaluate the graft and patient outcomes after liver transplantation (LT) using a right split graft, according to the type of venous drainage. From February 2000 to May 2006, 33 patients received 34 cadaveric right split liver grafts. According to the type of recipient pairs (adult/adult or adult/child), the right liver graft was deprived of the MHV or not. The first group (GI, n = 15) included grafts with only the right hepatic vein (RHV) outflow, the second (GII, n = 18) included grafts with both right and MHV outflows. The 2 groups were similar for patient demographics, initial liver disease, and donor characteristics. In GI and GII, graft-to-recipient-weight ratio (GRWR) was 1.2 ± 0% and 1.6 ± 0.3% (P < 0.05), and cold ischemia time was 10 hours 55 minutes ± 2 hours 49 minutes and 10 hours 47 minutes ± 3 hours 32 minutes, respectively (P = not significant). Postoperative death occurred in 1 patient in each group. Vascular complications included anastomotic strictures: 2 portal vein (PV), 1 hepatic artery (HA), and 1 RHV anastomotic strictures; all in GI. Biliary complications occurred in 20% and 22% of the patients, in GI and GII, respectively (P = not significant). There were no differences between both groups regarding postoperative outcome and blood tests at day 1-15 except for a significantly higher cholestasis in GI. At 1 and 3 yr, patient survival was 94% for both groups and graft survival was 93% for GI and 90% for GII (P = not significant). In conclusion, our results suggest that adult right SLT without the MHV is safe and associated with similar long-term results as compared with those of the right graft including the MHV, despite that early liver function recovered more slowly. Technical refinements in outflow drainage should be evaluated in selected cases. Liver Transpl 13:829,837, 2007. © 2007 AASLD. [source] Detection of HCV antigens in liver graft: Relevance to the management of recurrent post-liver transplant hepatitis CLIVER TRANSPLANTATION, Issue 11 2006Alberto Grassi The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic diagnosis and influence the clinical management of post-liver transplantation (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients with post-LT liver disease were studied. Histologic coding was: hepatitis (126), rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and 74% of cases after more than 180 days. Overall, HCV-Ag were detected more frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical diagnosis of recurrent hepatitis (RHC) was made despite inconclusive histopathologic diagnosis. Multivariate analysis identified the percentage of HCV-Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P = 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive hepatocytes ,50% as the only independent predictor for nonresponse (P < 0.001) in 26 patients treated with ,-interferon plus ribavirin. In conclusion, HCV reinfection occurs early post-LT, reaching its peak within 6 months. Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of hepatitis when the histologic features are not conclusive. A high number of infected cells, independently from the genotype, represents a negative predictive factor of response to antiviral treatment. Liver Transpl, 2006. © 2006 AASLD. [source] Hematopoietic stem cells mobilized by granulocyte colony-stimulating factor partly contribute to liver graft regeneration after partial orthotopic liver transplantationLIVER TRANSPLANTATION, Issue 7 2006Feng Liu On the basis of the recently recognized potential of hematopoietic stem cells (HSCs) to give rise to hepatocytes, we investigated whether HSCs mobilized by granulocyte colony-stimulating factor (G-CSF) or G-CSF per se could contribute to faster recovery and promote tissue reparation after rats' (cross-sex) partial orthotopic liver transplantation (PLTx). Sex-mismatched (female to male) syngeneic rat PLTx was established. The recipients were repeatedly administrated recombinant G-CSF for 5 consecutive days before (G-CSF + PLTx group) and after PLTx (PLTx + G-CSF group). Compared with those in PLTx group, CD34+ cells in peripheral blood and portal tract region increased from day 1 to 7 after transplantation in G-CSF + PLTx group and from day 3 to 14 after transplantation in PLTx + G-CSF group, respectively, which suggested that CD34+ HSCs were mobilized and migrated into liver graft. Compared with that in G-CSF + PLTx and PLTx groups, there was a higher survival rate in the PLTx + G-CSF group. On day 3 after surgery, the level of aspartate aminotransferase and alanine aminotransferase were lower, whereas the mitosis index, proliferating cell nuclear antigen,positive nuclei, bromodeoxyuridine (BrdU) incorporation, and graft-to-recipient weight ratio were higher in the PLTx + G-CSF group. In contrast, these parameters had no significant difference between G-CSF + PLTx and PLTx groups. To define the origin of proliferating cells reconstituting liver after injury, sry+ (sex-determining region for Y chromosome) and sry+/cytokeratin 19+ (CK19) cells were quantitated. Higher percentage of sry+ and sry+/CK19+ cells in PLTx + G-CSF was detected than in G-CSF + PLTx groups on day 14 after surgery, although the liver engraftment rate still remained rather low. Some of the sry+/CK19+ cells in the portal tract areas were similar to hepatic oval cells/cholangiocytes. In conclusion, G-CSF administration after PLTx greatly improved survival rate and liver regeneration of partial graft, partly by its mobilizing HSCs into the injured liver to differentiate into hepatocytes through hepatic oval cells'/cholangiocytes' engraftment. Liver Transpl 12:1129,1137, 2006. © 2006 AASLD. [source] Five-year follow-up of a hepatitis B virus-positive recipient of hepatitis B surface antigen-positive living donor liver graftLIVER TRANSPLANTATION, Issue 6 2006Shin Hwang The shortage of cadaveric donor organs has led to the use of living donors and marginal cadaveric donors. To date, there have been only 2 reports on the use of hepatitis B surface antigen (HBsAg)-positive liver grafts. Here we describe the 5-yr posttransplantation sequence of a hepatitis B virus (HBV)-positive recipient who received an HBsAg-positive living donor liver graft. A 43-yr-old HBV-positive patient with hepatorenal syndrome received a living donor liver graft in October 2000 from a 27-yr-old HBsAg-positive carrier with no clinical evidence of HBV infection other than the serologic markers. The recipient recovered slowly after liver transplantation (LT). Recipient serum HBsAg was continuously positive despite anti-HBV therapy with high-dose hepatitis B immunoglobulin (HBIG) and lamivudine. The patient was also treated with famciclovir and interferon; to date, a final regimen of lamivudine and adefovir has kept liver function stable for 20 months. The recipient has lived for 64 months after transplantation. The donor has not revealed any clinical evidence of active hepatitis during follow-up. In conclusion, our result implicates that a recipient of liver graft from an HBsAg-positive carrier may survive for a long period following antiviral therapy with lamivudine and adefovir. Considering this living donor case and previously reported cases, the use of an HBsAg-positive cadaveric liver graft may deserve attention when no other donor is available. Liver Transpl 12:993,997, 2006. © 2006 AASLD. [source] Characterization of human liver dendritic cells in liver grafts and perfusatesLIVER TRANSPLANTATION, Issue 3 2006Brenda M. Bosma It is generally accepted that donor myeloid dendritic cells (MDC) are the main instigators of acute rejection after organ transplantation. The aim of the present study was to characterize MDC in human donor livers using liver grafts and perfusates as a source. Perfusates were collected during ex vivo vascular perfusion of liver grafts pretransplantation. MDC, visualized in wedge biopsies by immunohistochemistry with anti-BDCA-1 monoclonal antibody (mAb), were predominantly observed in the portal fields. Liver MDC, isolated from liver wedge biopsies, had an immature phenotype with a low expression of CD80 and CD83. Perfusates were collected from 20 grafts; perfusate mononuclear cells (MNC) contained 1.5% (range, 0.3-6.6%) MDC with a viability of 97 ± 2%. Perfusates were a rich source of hepatic MDC since 0.9 × 106 (range, 0.11-4.5 × 106) MDC detached from donor livers during vascular perfusion pretransplantation. Perfusate MDC were used to further characterize hepatic MDC. Perfusate MDC expressed less DC-LAMP (P = 0.000), CD80 (P = 0.000), CD86 (P = 0.003), and CCR7 (P = 0.014) than mature hepatic lymph node (LN) MDC, and similar CD86 (P = 0.140) and CCR7 (P = 0.262) as and more DC-LAMP (P = 0.007) and CD80 (P = 0.002) than immature blood MDC. Perfusate MDC differed from blood MDC in producing significantly higher amounts of interleukin (IL)-10 in response to lipopolysaccharide (LPS), and in being able to stimulate allogeneic T-cell proliferation. In conclusion, human donor livers contain exclusively immature MDC that detach in high numbers from the liver graft during pretransplantation perfusion. These viable MDC have the capacity to stimulate allogeneic T-cells, and thus may represent a major player in the induction of acute rejection. Liver Transpl 12: 384,393, 2006. © 2006 AASLD. [source] Liver laceration associated with severe seizures after living donor liver transplantationLIVER TRANSPLANTATION, Issue 1 2006Kazushige Sato Hemorrhagic complications commonly occur early after liver transplantation (LT), sometimes requiring emergent relaparotomy. However, active bleeding from the liver graft itself is a rare but life-threatening complication after living donor liver transplantation (LDLT). We report an unusual case of liver laceration with massive bleeding, associated with severe epileptic seizures as a result of tacrolimus-induced leukoencephalopathy, after LDLT. The patient was successfully rescued by conventional surgical management without a second transplantation. In conclusion, to our knowledge this is the first reported case of graft rupture due to immunosuppression-associated leukoencephalopathy after LT. Liver Transpl12:152,155, 2006. © 2005 AASLD. [source] Cryopreserved iliac artery is indispensable interposition graft material for middle hepatic vein reconstruction of right liver graftsLIVER TRANSPLANTATION, Issue 6 2005Shin Hwang Cryopreserved iliac vein grafts (IVGs) have often been used for reconstruction of middle hepatic vein (MHV) branches in right liver grafts, but their storage pool has often been exhausted in our institution due to the low incidence of deceased donor organ procurement. To overcome this shortage of IVG, we started to use cryopreserved iliac artery graft (IAG). During September and October 2004, we carried out 41 cases of adult living donor liver transplantation, including 29 right lobe grafts with MHV reconstruction. Interposition vessel grafts were autologous vein (n = 6), IVG (n = 13), and IAG (n = 10). IAG was used in 3 (21%) of 13 cases during the first month. For the next month, it was more frequently used (7 [44%] of 16) because handling of cryopreserved IAG was not difficult and its outcome was favorable. On follow-up with computed tomography for 3 months, outflow disturbance occurred in 1 (17%) of 6 autologous vein cases, in 2 (15%) of 13 IVG cases, and in 1 (10%) of 10 IAG cases. Two-month patency rate of IAG was not lower than that of IVG. In conclusion, we feel that cryopreserved IAG can be used as an interposition vessel graft for MHV reconstruction of right liver graft when cryopreserved IVG is not available. (Liver Transpl 2005;11:644,649.) [source] Transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a non-heart beating donorLIVER TRANSPLANTATION, Issue 6 2005Olivier Detry Transmission of an undiagnosed cancer with solid organ transplantation is a rare but dreadful event. In this paper the authors report the transmission of an undiagnosed sarcoma to recipients of kidney and liver grafts procured in a Maastricht category 3 non-heart beating donor. To the authors' knowledge this case is the first report of such a transmission with a liver graft procured in a non-heart beating donor. The cancer transferal was diagnosed 1 year after transplantation in the recipients of the liver and of one kidney. The liver recipient died from multiple organ failure after a failed attempt of tumor resection. The kidney recipient underwent immunosuppression withdrawal and transplantectomy. Non-heart beating donors should not be particularly at risk for undiagnosed cancer transmission if the procurement is performed according to the same rules of careful inspection of the abdominal and thoracic organs. After diagnosis of donor cancer transmission, kidney recipients should have the graft removed, and immunosuppression should be interrupted. The management of liver graft recipients is very difficult in this setting, and long-term survival was very rarely reported. (Liver Transpl 2005;11:696,699.) [source] Preclinical experiment of auxiliary partial orthotopic liver transplantation as a curative treatment for hemophiliaLIVER TRANSPLANTATION, Issue 5 2005Saiho Ko The cause of hemophilia is deficiency of coagulation factor VIII production in the liver, which can be cured by liver transplantation. Because the hepatic function of hemophilia patients is quite normal except for production of factor VIII, auxiliary partial orthotopic liver transplantation (APOLT) is beneficial in that patient survival is secured by preserving native liver even in the event of graft loss. However, it is not known whether the graft of APOLT would be enough to cure hemophilia. We evaluated the efficacy and feasibility of APOLT for hemophilia in a canine hemophilia A model that we established. Partial left liver graft was taken from the normal donor (blood factor VIII activity > 60%). The graft was transplanted to the hemophilia beagle dog (blood factor VIII activity < 5%) after resection of the left lobe preserving native right lobe. Changes in time of blood factor VIII activity and liver function parameters were observed after APOLT. APOLT and perioperative hemostatic management were successfully performed. The blood factor VIII activity increased to 30% after APOLT, and was sustained at least 6 weeks throughout the observation period without symptoms of bleeding. The result demonstrated sustained production of factor VIII in the hemophilia recipient after APOLT. Transplantation of approximately one third of whole liver resulted in cure of hemophilia. In conclusion, it is suggested that APOLT would be feasible as a curative treatment of hemophilia A to improve quality of life of the patients. (Liver Transpl 2005;11:579,584.) [source] Simplified standardized technique for living donor liver transplantation using left liver graft plus caudate lobeLIVER TRANSPLANTATION, Issue 11 2004Shin Hwang Concomitant resection of the caudate lobe (CL) would increase the liver mass in the left liver graft. We tried to define a simplified standardized technique for adult living donor liver transplantation using the extended left lobe (ELL) plus CL (ELLC) through a prospective study of 27 consecutive ELLC graft cases in 2003. Donor CL was dissected toward the 10 o'clock direction and transected at the midpoint between the trunks of the right hepatic vein (RHV) and the middle hepatic vein (MHV). This orthodox transection was performed in 18 cases, but the transection plane was moved left in 9 cases. Compared with conventional left liver implantation, there was no additional reconstruction except for single revascularization of the largest short hepatic vein of the CL (V1) in 21 cases. On 1-week computed tomography (CT) images, the perfusion states of the CL portion were good in 15 cases, fair in 7 cases, and poor in 5 cases. Regeneration of the CL portion during the 1st week was +43%, +18%, and ,10% in the good, fair, and poor perfusion groups, respectively. There were positive correlations among the perfusion state of the CL, the location of the CL transection plane, and the width of the CL portion that was attached to the left liver graft. CL implantation resulted in a mean gain of graft mass by 5.9% in the left liver at the time of operation and by 3.9% after 1 week. There were no donor complications, and 25 recipients (93%) survive to date. In conclusion, this simplified standardized technique was feasible for most of the living donor livers and required only 1 additional reconstruction of the V1. (Liver Transpl 2004;10:1398,1405.) [source] Detection of recipient's cells in liver graft using antibodies to mismatched HLA class I antigensLIVER TRANSPLANTATION, Issue 11 2004Alberto Grassi Engraftment by recipient's (R) cells has been already demonstrated in gender mismatched liver grafts using fluorescence in situ hybridization (FISH), with contrasting results concerning epithelial cells. Mismatch for human leukocyte antigen (HLA) class I (HLA-I) is quite common in patients with orthotopic liver transplantation (OLT). We thus aimed to assess whether monoclonal antibodies (MoAbs), currently employed in the HLA typing process, could be used to study the dynamics of R cells in liver grafts. A total of 50 frozen liver biopsies from 37 patients receiving a HLA mismatch liver were tested. Biopsies were obtained from 3 days to more than 360 days after OLT. Frozen sections of graft biopsies were stained using an immunoperoxidase technique with the proper MoAbs. In selected cases, a double immunofluorescence was also performed. Circulating R blood cells and sinusoidal cells were occasionally observed in liver biopsies obtained within 10 days after OLT and were commonly detected after 1 month. The number of sinusoidal cells continued to increase up to 6 months, as shown on serial biopsies. On the whole, R blood cells and R sinusoidal cells were detected in 86% and 82% of the biopsies, respectively. R hepatocytes and biliary cells were detected after 40 and 60 days after OLT, respectively, in 14% (hepatocytes), 8% (bile ducts), and 12% (proliferating bile ducts) of the biopsies. R hepatocytes presented as single cells or groups of few cells; their number was lower than 1% and apparently did not increase with time after OLT. In conclusion, it is possible to detect R cells in liver graft using MoAbs to specific mismatched HLA-I alleles. R sinusoidal cells start to appear after 10 days and are commonly observed after 1 month; bile duct cells and hepatocytes appear later and their number does not increase with time. Engraftment by R epithelial cells seems to be less important than previously reported. (Liver Transpl 2004;10:1406,1414.) [source] Advances in adult living donor liver transplantation: A review based on reports from the 10th anniversary of the adult-to-adult living donor liver transplantation meeting in TokyoLIVER TRANSPLANTATION, Issue 6 2004Yasuhiko Sugawara In 1993, the Shinshu Group performed the first successful adult-to-adult living donor liver transplantation (LDLT). During the first 10 years of LDLT, many technical innovations have been reported. The major limitation of LDLT for adult recipients is the size of the graft. To overcome the problem, several graft types were designed, including left liver graft with caudate lobe, right liver, modified right liver, and right lateral sector and dual grafts. The necessity and criteria of reconstruction of middle hepatic vein is still on debate in right liver graft without trunk of middle hepatic vein. Biliary reconstruction remains a significant source of morbidity in LDLT. Donor safety must always be the primary consideration in LDLT and the selection criteria and management of the living donor must continue to be refined. On February 21, 2004, the 10th anniversary of the adult-to-adult LDLT meeting was held in Tokyo to review the accumulated experience and the presented information is summarized. (Liver Transpl 2004;10:715,720.) [source] Tailoring donor hepatectomy per segment 4 venous drainage in right lobe live donor liver transplantationLIVER TRANSPLANTATION, Issue 6 2004See Ching Chan Including the middle hepatic vein (MHV) in the right lobe liver graft for adult-to-adult live donor liver transplantation provides more functional liver by securing adequate venous drainage. Donor outcome of this procedure in relation to different venous drainage patterns of segment 4 is unknown. Modification of graft harvesting technique by preserving segment 4b hepatic vein (V4b) in theory compensates for unfavorable venous drainage patterns. Consecutive 120 right lobe live donors were included. Computed tomography was studied in detail to assign each donor to one of the three types of the Nakamura classification of venous drainage pattern of segment 4. Type I drainage was mainly via the left hepatic vein (LHV), type II drainage was equally into the MHV and LHV, and type III drainage was predominantly into the MHV. Any distinct umbilical vein was also noted. In the early part of the series, the V4b draining into the MHV was divided to provide a long MHV stump in the graft. In the later part of the series, prominent V4b draining into the MHV was preserved in the donor as far as possible. Donor outcomes were measured by peak values of prothrombin time (PT), serum bilirubin and transaminases levels. There was no donor mortality. Type I donors (n=69) had the best outcome with peak PT of 17.9 sec (range 12.3,23.3 sec). Type II donors (n=44) had peak PT of 18.5 sec (range 15.4,24.4 sec). When V4b was preserved in type II donors (n=19), the peak PT (18.0 sec, range 15.4,20.7 sec) became significantly lower than that of type II donors who had V4b sacrificed (20.3 sec, range 16.2,24.4 sec) (P=0.001). A distinct umbilical vein (n=91, 75.8%) was insignificant for donor outcome measured by peak PT. Multivariate analysis identified that type II donors with V4b sacrificed (n=25), type III donors (n=7), and the first 50 cases had less favorable outcomes. In conclusion, unfavorable venous drainage patterns were one of the independent factors compromising postoperative donor liver function, but was circumvented by preservation of V4b. (Liver Transpl 2004;10:755,762.) [source] Metabolic changes in the liver graft monitored continuously with microdialysis during liver transplantation in a pig modelLIVER TRANSPLANTATION, Issue 5 2002Grzegorz Nowak MD Microdialysis provides the opportunity to continuously monitor metabolic changes in tissue. The aim of the study is to monitor metabolic changes in the liver graft over time during transplantation in a pig model. Fourteen littermate female pigs with a body weight of 30 to 34 kg were used for seven orthotopic liver transplantations. Intrahepatic implantation of a microdialysis catheter into the liver graft was performed in the donor. Microdialysis samples were collected at 20-minute intervals during the donor operation, cold preservation, and for 7 hours after reperfusion in the recipient. Glucose, lactate, pyruvate, and glycerol concentrations were measured. After cold perfusion, glucose, lactate, and glycerol levels increased, whereas pyruvate levels decreased rapidly. During cold storage, glucose and glycerol levels increased, whereas lactate levels remained stable and pyruvate levels were undetectable. During implantation of the liver graft, glucose, lactate, and glycerol levels showed an accelerated increase. After portal reperfusion, glucose, lactate, and glycerol levels continued to increase for another 40 to 60 minutes, after which they decreased and finally settled at normal levels. At this time, pyruvate levels increased, with a peak within 2 hours after reperfusion, and then decreased to normal levels. Calculated lactate-pyruvate ratio increased after cold perfusion and remained stable during cold storage. During rewarming, it showed an accelerated increase, but after reperfusion, it decreased rapidly. Rewarming and reperfusion are most harmful to the liver, reflected by an accelerated increase in glucose and glycerol levels and lactate-pyruvate ratio. High intrahepatic glucose levels during ischemia appear to be a liver-specific event, which may represent glycogen degradation in injured hepatocytes. [source] Outflow reconstruction in recipients of right liver graft from living donorsLIVER TRANSPLANTATION, Issue 2 2002Yasuhiko Sugawara MD Right-lobe transplantation is now a commonly used procedure in living donor liver transplantation (LDLT) to adult recipients. However, the risk for outflow obstruction is still an issue in LDLT. The right hepatic vein (RHV) was anastomosed end to end to the graft hepatic vein without unfavorable tension on the anastomosis. The anterior wall of the recipient hepatic vein was incised longitudinally, and a V-shaped vein graft was patched to form a wide and long orifice. This new hepatic venoplasty was used in 14 adult patients who received right liver grafts and gave good results without stenosis of the hepatic venous anastomosis or other complications. Our new technique may be useful in recipients of a right liver graft when the recipient or graft RHV is not long enough. [source] Postoperative tracheal extubation after orthotopic liver transplantationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2001M. Glanemann Background: The duration of postoperative mechanical ventilation and its influence on pulmonary function in liver transplant recipients is still debated controversially. Methods: We retrospectively analyzed the incidence of immediate tracheal extubation, prolonged mechanical ventilation (>24 h following surgery), and episodes of reintubation in 546 patients who underwent orthotopic liver transplantation (OLT) at our institution. Results: Immediate tracheal extubation in the operating theater was achieved in 18.7% of patients, and prolonged mechanical ventilation was required by 11.2% of patients. In these, median time of extubation was 49.5 h, whereas the remaining 70.1% of patients required ventilation support for a median 5 h after OLT. As risk factors for prolonged mechanical ventilation we identified the indications of acute liver failure and retransplantation, as well as factors such as mechanical ventilation prior to OLT, massive intraoperative bleeding, and severe reperfusion injury of the liver graft. The incidence of reintubation was 8.8% in patients who were immediately extubated following surgery, and 13.1% in patients who underwent extubation within 24 h. The incidence was significantly increased in patients requiring prolonged mechanical ventilation (36.1%). Conclusions: Immediate tracheal extubation was safe and well tolerated. The incidence of reintubation was not increased when compared to patients in whom extubation succeeded later. However, special attention should be given to transplant recipients presenting in reduced clinical condition at the time of OLT, undergoing complicated surgery, or receiving liver allografts with severe reperfusion injury because of an increased risk for prolonged mechanical ventilation. [source] Arterial anastomosis in a pediatric patient receiving a right extended split liver transplant: A case reportPEDIATRIC TRANSPLANTATION, Issue 4 2009Roberto Verzaro Abstract:, We report a case of a pediatric patient who received a right-extended liver transplant. The size of the recipient hepatic artery did not match with the donor right hepatic arterial stump. Moreover, recipient arterial anatomy made the direct anastomosis difficult or at increased risk for complications. The recipient's splenic artery was then mobilized, divided and anastomosed to the donor's right hepatic artery. The spleen was preserved and revascularization through collaterals is demonstrated by Angio CT Scan. Doppler US of the transplanted liver demonstrated good flow through the liver and the patient was discharged with perfect liver function. Splenic artery is perfectly suited for hepatic artery anastomosis. The use of splenic artery is favored in particular situations as in the case of a pediatric recipient receiving a right-extended liver graft with small caliber artery. [source] | ||||||||||||||||||||||||||||