Home About us Contact
|
Home About us Contact | ||
|
|
||
Liver Recipients (liver + recipient)
Kinds of Liver Recipients Selected AbstractsA Model for Graft Allocation After Intra-Operative Mortality of an Intended Living Donor Liver RecipientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2005Peter S. Knight No abstract is available for this article. [source] Active Immunization to Prevent De Novo Hepatitis B Virus Infection in Pediatric Live Donor Liver RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2007C.-C. Lin This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty received grafts from anti-HBc(+) donors, and another 30 received grafts from anti-HBc(,) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti-HBc(+) grafts for about 2 years. Forty-seven (78%) recipients achieved high levels of anti-HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti-HBc(,) graft and another received an anti-HBc(+) graft. Both recipients were in the lower anti-HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow-up period was 51 months in recipients with anti-HBc(,) grafts and 57 months in those with anti-HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti-HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT. [source] Themes of liver transplantation,HEPATOLOGY, Issue 6 2010Thomas E. Starzl Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as healthcare standards, the ethical, legal, equity, and the other humanism issues of Theme V have been resolved less conclusively than the medical-scientific problems of Themes I-IV. HEPATOLOGY 2010 [source] Impact of donor infections on outcome of orthotopic liver transplantationLIVER TRANSPLANTATION, Issue 5 2003Michael Angelis Infection occurs when microbial agents enter the host, either through airborne transmission or by direct contact of a substance carrying the infectious agent with the host. Human body fluids, solid organs, or other tissues often are ideal vectors to support microbial agents and can transmit infections efficiently from donor to recipient. In the case of blood transfusion and tissue transplantation, the main consequence of such a transmission is infection of the recipient. However, in the case of solid-organ transplantation, and particularly for liver transplantation, donor infections are not only transmitted to the recipient, the donor infection also may affect the donated liver's preservability and subsequent function in the recipient irrespective of the systemic consequences of the infection. In addition, solid organ recipients of infected organs are less able to respond to the infectious agent because of their immunosuppressive treatment. Thus, transmission of infections from organ donor to liver recipient represents serious potential risks that must be weighed against a candidate's mortality risk without the transplant. However, the ever-increasing gap between the number of donors and those waiting for liver grafts makes consideration of every potential donor, regardless of the infection status, essential to minimize waiting list mortality. In this review, we will focus on assessing the risk of transmission of bacterial, fungal, viral, and parasitic infectious agents from cadaveric liver donors to recipients and the effect such a transmission has on liver function, morbidity, and mortality. We will also discuss risk-benefit deliberations for using organs from infected donors for certain types of recipients. These issues are critically important to maximize the use of donated organs but also minimize recipient morbidity and graft dysfunction. [source] Extended Survival by Urgent Liver Retransplantation after Using a First Graft with Metastasis from Initially Unrecognized Donor SarcomaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2005Jorge A. Ortiz A 58-year-old man underwent orthotopic liver transplantation for polycystic liver disease. Shortly after the procedure, it was discovered that the donor harbored a sarcoma of the aortic arch that had metastasized to the spleen, and bilateral renal cell carcinomas. The two sole organ recipients, our liver recipient and a lung recipient at another institution, were both listed for urgent retransplantation, which they received from the same second donor. The liver explant contained metastatic sarcoma. Twenty-four months survival following lung retransplantation has been previously reported. We report the 76-month disease-free survival in the liver recipient. [source] Factor V Leiden and hepatic artery thrombosis after liver transplantationCLINICAL TRANSPLANTATION, Issue 1 2006Ty B Dunn Abstract:, Factor V Leiden (FVL) and other thrombophilias can be acquired during liver transplantation and can have a significant impact on clinical outcomes as well as cost. Standard practice does not include screening deceased donors for heritable thrombophilias, even if they have a personal history of thrombosis. Here we report a case of hepatic artery thrombosis in a liver recipient whose native and donor livers were heterozygous for FVL. The patient subsequently underwent a successful retransplant. FVL and its variants are expressed phenotypically as activated protein C (APC) resistance. We believe that testing liver donors (deceased or living) for APC resistance , a surrogate marker for the most common liver-based thrombophilia , will reduce the incidence of thrombotic events by identifying a need for posttransplant prophylactic anticoagulation in patients at risk. The estimated cost of testing all liver donors in the US for APC resistance is less than the cost of two complications secondary to thrombosis. Testing for APC resistance may further improve outcome and reduce cost after liver transplantation. [source] Fractures and avascular necrosis before and after orthotopic liver transplantation: Long-term follow-up and predictive factors,HEPATOLOGY, Issue 4 2007Maureen M. J. Guichelaar With early posttransplant bone loss, orthotopic liver transplantation (OLT) recipients experience a high rate of fracturing and some avascular necrosis (AVN), but little is known about the incidence of and predictive factors for these skeletal complications. We studied 360 consecutive patients who underwent transplantation for primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and assessed both vertebral and nonvertebral (rib, pelvic, and femur) fractures in a protocolized fashion. Before OLT, 20% of the patients had experienced fracturing, and 1.4% of the patients had experienced AVN. Following OLT, there was a sharp increase in fracturing, with a 30% cumulative incidence of fractures at 1 year and 46% at 8 years after transplantation. In contrast to previous studies, there was a similar incidence of posttransplant vertebral and nonvertebral fractures. The greatest risk factors for posttransplant fracturing were pretransplant fracturing and the severity of osteopenia and posttransplant glucocorticoids. Nine percent of the liver recipients experienced AVN after OLT, and this correlated with pretransplant and posttransplant lipid metabolism, bone disease (bone mineral density and fracturing), and posttransplant glucocorticoids. A novel association between cholestasis and AVN was also identified, the mechanism for which is not known. Conclusion: Fortunately, recent years have seen an increase in the bone mass of liver recipients and, along with this, less fracturing and less AVN. Nonetheless, 25% of patients undergoing OLT for chronic cholestatic liver disease still develop de novo fractures after OLT; this situation demands an ongoing search for effective therapeutic agents for these patients. (HEPATOLOGY 2007.) [source] Double-dose double-phase use of second generation hepatitis B virus vaccine in patients after living donor liver transplantation: Not an effective measure in transplant recipientsHEPATOLOGY RESEARCH, Issue 1 2009Noriyo Yamashiki Aims:, Post-transplant active immunization for chronic hepatitis B patients has been attempted in several studies with controversial results. We assessed the effect of a double-dose double-phase vaccination regimen among partial living donor liver recipients. Methods:, Eighteen patients who underwent liver transplantation (LT) for chronic hepatitis B and two non-hepatitis B virus (HBV)-infected patients who received hepatitis B core antibody (HBcAb)-positive donor organs were recruited 18,78 months after LT. All were on hepatitis B immunoglobulin (HBIG) mono-prophylaxis before and throughout vaccination, to maintain hepatitis B surface antibody (HBsAb) titers of more than 100 IU/mL. Recombinant hepatitis B surface antigen vaccine (40 µg) was administered intramuscularly during weeks 0, 4, 8, 24, 28 and 32. Results:, The patients consisted of 15 males and five females with a median age of 52 (39,59) years. None developed a sufficient HBsAb titer above 500 IU/mL by week 48. In two patients whose maximum HBsAb titer increased to above 300 IU/mL, we attempted to skip HBIG, but shortly thereafter the titer dropped below 100 IU/mL and HBIG administration was resumed. Although the HBIG dose was reduced during and after vaccination, cessation of administration was not achieved. Conclusion:, Double-dose double-phase use of second generation recombinant vaccine was not effective in this study population. The selected population should be targeted for a conventional vaccine regimen, and different approaches, such as strong adjuvant or pre-S containing protein, should be further tested in a larger number of patients after LT for chronic hepatitis B. [source] Relationships of tacrolimus pharmacokinetic measures and adverse outcomes in stable adult liver transplant recipientsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2006C. Dansirikul PhD Summary Background and objectives:, Alternative measures to trough concentrations [non-trough concentrations and limited area under the concentration,time curve (AUC)] have been shown to better predict tacrolimus AUC. The aim of this study was to determine if these are also better predictors of adverse outcomes in long term liver transplant recipients. Methods:, The associations between tacrolimus trough concentrations (C0), non-trough concentrations (C1, C2, C4, C6/8), and AUC0,12 and the occurrence of hypertension, hyperkalaemia, hyperglycaemia and nephrotoxicity were assessed in 34 clinically stable liver transplant patients. Results and discussion:, The most common adverse outcome was hypertension, prevalence of 36%. Hyperkalaemia and hyperglycaemia had a prevalence of 21% and 13%, respectively. A sequential population pharmacokinetic/pharmacodynamic approach was implemented. No significant association between predicted C0, C1, C2, C4, C6/8 or AUC0,12 and adverse effects could be found. Tacrolimus concentrations and AUC measures were in the same range in patients with and without adverse effects. Conclusions:, Measures reported to provide benefit, preventing graft rejection and minimizing acute adverse effects in the early post-transplant period, were not able to predict adverse effects in stable adult liver recipients whose trough concentrations were maintained in the notional target range. [source] Identification of operationally tolerant liver transplant recipients,LIVER TRANSPLANTATION, Issue S2 2010Alberto Sánchez-Fueyo KEY POINTS: (1) Liver allografts exhibit intrinsic tolerogenic properties that result in their spontaneous acceptance in many experimental animal models. (2) In clinical transplantation, liver allografts require milder immunosuppression (IS) regimens than other organs, are remarkably resistant to antibody-mediated rejection, and only very rarely are lost because of immunological insults. (3) A fraction of stable liver transplant recipients can withdraw from all IS therapy and then maintain normal graft function and not experience rejection. This phenomenon is known as spontaneous operational tolerance. (4) The intentional discontinuation of IS in stable liver transplant recipients has led to successful weaning in almost 20% of recipients, but the true prevalence of spontaneous operational tolerance in unselected recipients is still unknown. (5) The prevalence could be higher in pediatric recipients undergoing transplantation before 1 year of age and in adult recipients with more than 10 years of posttransplant follow-up. (6) Rejection occurring during medically supervised IS weaning trials tends to be mild and, in the overwhelming majority of cases, can be easily resolved without the administration of high-dose IS. (7) Tolerant liver recipients exhibit specific transcriptional patterns in peripheral blood and in liver tissue that may constitute future diagnostic markers of tolerance. (8) There is still no formal proof that the discontinuation of low-dose IS in long-term surviving liver recipients improves the morbidity and mortality rates associated with IS therapy. Liver Transpl 16:S82-S86, 2010. © 2010 AASLD. [source] Graft weight/recipient weight ratio: How well does it predict outcome after partial liver transplants?LIVER TRANSPLANTATION, Issue 9 2009Mark J. Hill Partial graft liver recipients with graft weight/recipient weight (GW/RW) ratios < 0.8% are thought to have a higher incidence of postoperative complications, including small-for-size syndrome (SFSS). We analyzed a cohort of such recipients and compared those with GW/RW < 0.8% to those with GW/RW , 0.8%. Between 1999 and 2008, 107 adult patients underwent partial graft liver transplants: 76 from live donors [living donor liver transplantation (LDLT)] and 31 from deceased donors [split liver transplantation (SLT)]. Of these, 22 had GW/RW < 0.8% (12 with LDLT and 10 with SLT), and 85 had GW/RW , 0.8% (64 with LDLT and 21 with SLT). The baseline demographics and median length of follow-up were similar. SFSS developed in 3 recipients with GW/RW < 0.8% (13.6%) and in 8 recipients with GW/RW , 0.8% (9.4%; P = not significant). Other early complications were similar between the 2 groups. Inflow modification with splenic artery occlusion was performed in 13 recipients: 7 with GW/RW < 0.8% and 6 with GW/RW , 0.8%. Graft survival at 1 year post-transplant did not differ (91% versus 92%; P = not significant). In conclusion, GW/RW did not appear to be the only determinant of outcome after partial liver transplantation. Using techniques such as inflow modification may help to prevent some of the problems seen with smaller grafts. Liver Transpl 15:1056,1062, 2009. © 2009 AASLD. [source] Early immunological monitoring after pediatric liver transplantation: Cytokine immune deviation and graft acceptance in 40 recipientsLIVER TRANSPLANTATION, Issue 3 2007Jérémie Gras Cytokine deviation may be a factor contributing to graft acceptance. We analyze, in the context of liver transplantation, circulating cytokine levels and their mRNA precursors in liver biopsy samples to study a putative correlation with early immunologic outcome. Forty primary pediatric liver recipients were submitted to a prospective immune monitoring protocol, including 8 of 40 patients with an early, biopsy-proven acute rejection episode. The 32 patients with graft acceptance showed markedly increased interleukin (IL)-10 blood levels at 2 hours after reperfusion on days 1 and 4 after transplantation as compared with baseline, whereas patients with graft rejection only exhibited increased IL-10 levels at 2 hours. A good correlation was observed between IL-10 peripheral levels and levels ascertained by IL-10 reverse transcriptase,polymerase chain reaction at 2 hours and on day 7. Patients with graft acceptance also showed a decrease in interferon gamma (IFN-,) at 1 and 2 hours after reperfusion on days 1, 4, 7, 14, and 28 after transplantation. One patient with graft tolerance who had subsequent immunosuppression withdrawal after posttransplantation lymphoproliferative disease showed a similar intraoperative IL-10 pattern, whereas posttransplantation tumor necrosis factor alpha and IFN-, levels greatly decreased. The occurrence of cytokine immune deviation may therefore be related to early graft acceptance in children who receive liver transplants. Liver Transpl 13:426,433, 2007. © 2007 AASLD. [source] Transthyretin-derived amyloid deposition on the gastric mucosa in domino recipients of familial amyloid polyneuropathy liverLIVER TRANSPLANTATION, Issue 2 2007Yo-ichi Takei Familial amyloid polyneuropathy (FAP) is a form of hereditary generalized amyloidosis. Liver tissue explanted from FAP patients has normal structure and function, except for the production of amyloidogenic variant transthyretin (TTR), and domino liver transplantation (DLT) using grafts from FAP patients was first performed in 1995. FAP symptoms usually develop in genetically determined individuals after the age of 20, but it is difficult to estimate when FAP symptoms will appear in domino recipients. Concerning this problem, histological findings showing amyloid deposition have recently been obtained in a few domino recipients of FAP livers. This study investigated the presence of de novo amyloid deposition in the gastroduodenal mucosa of domino recipients transplanted at our institution. Biopsy of gastroduodenal mucosa was carried out in 5 recipients of FAP livers and TTR-derived amyloid deposits were detected in 2 patients, both of whom had undergone DLT 47 months previously. In FAP liver recipients, de novo systemic amyloid deposition may begin much sooner than previously supposed. Therefore, careful follow-up of domino recipients of FAP livers is required. Liver Transpl, 2006. © 2006 AASLD. [source] Cardiovascular risk factors after liver transplantationLIVER TRANSPLANTATION, Issue S2 2005Santiago J. Muñoz Key Points 1Yearly screening of liver recipients with serum cholesterol, triglycerides, and lipoproteins, and assessment for risk factors for atherosclerotic cardiovascular disease, is an important component of comprehensive post transplant care. 2Revised guidelines and target levels of LDL-cholesterol levels specific for moderate and high cardiovascular risk patients have been recently revised. 3Transplant physicians should be aware of advances in the management of post transplant arterial hypertension, diabetes mellitus, obesity, and nicotine dependence. (Liver Transpl 2005;11:S52,S56.) [source] Immunosuppression for liver transplantation in HCV-infected patients: Mechanism-based principlesLIVER TRANSPLANTATION, Issue 11 2005Bijan Eghtesad We retrospectively analyzed 42 hepatitis C virus (HCV)-infected patients who underwent cadaveric liver transplantation under two strategies of immunosuppression: (1) daily tacrolimus (TAC) throughout and an initial cycle of high-dose prednisone (PRED) with subsequent gradual steroid weaning, or (2) intraoperative antithymocyte globulin (ATG) and daily TAC that was later space weaned. After 36 ± 4 months, patient and graft survival in the first group was 18/19 (94.7%) with no examples of clinically serious HCV recurrence. In the second group, the three-year patient survival was 12/23 (52%), and graft survival was 9/23 (39%); accelerated recurrent hepatitis was the principal cause of the poor results. The data were interpreted in the context of a recently proposed immunologic paradigm that is equally applicable to transplantation and viral immunity. In the framework of this paradigm, the disparate hepatitis outcomes reflected different equilibria reached under the two immunosuppression regimens between the relative kinetics of viral distribution (systemically and in the liver) and the slowly recovering HCV-specific T-cell response. As a corollary, the aims of treatment of the HCV-infected liver recipients should be to predict, monitor, and equilibrate beneficial balances between virus distribution and the absence of an immunopathologic antiviral T-cell response. In this view, favorable equilibria were accomplished in the nonweaned group of patients but not in the weaned group. In conclusion, since the anti-HCV response is unleashed when immunosuppression is weaned, treatment protocols that minimize disease recurrence in HCV-infected allograft recipients must balance the desire to reduce immunosuppression or induce allotolerance with the need to prevent antiviral immunopathology. (Liver Transpl 2005;11:1343,1352.) [source] MELD,Moving steadily towards equality, equity, and fairnessLIVER TRANSPLANTATION, Issue 5 2005James Neuberger Background and aims: A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list. Methods: The MELD model predicts liver disease severity based on serum creatinine, serum total bilirubin, and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis. In this study, we prospectively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant candidates with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November, 1999, and December, 2001. Results: In this study cohort with chronic liver disease, 412 (12%) died during the 3-month follow-up period. Waiting list mortality increased directly in proportion to the listing MELD score. Patients having a MELD score <9 experienced a 1.9% mortality, whereas patients having a MELD score > or =40 had a mortality rate of 71.3%. Using the c-statistic with 3-month mortality as the end point, the area under the receiver operating characteristic (ROC) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh (CTP) score (P < 0.001). Conclusions: These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers.(Gastroenterology 2003;124:91,96.) Context: The Model for Endstage Liver Disease (MELD) score serves as the basis for the distribution of deceased-donor (DD) livers and was developed in response to "the final rule" mandate, whose stated principle is to allocate livers according to a patient's medical need, with less emphasis on keeping organs in the local procurement area. However, in selected areas of the United States, organs are kept in organ procurement organizations (OPOs) with small waiting lists and transplanted into less-sick patients instead of being allocated to sicker patients in nearby transplant centers in OPOs with large waiting lists. Objective: To determine whether there is a difference in MELD scores for liver transplant recipients receiving transplants in small vs large OPOs. Design and setting: Retrospective review of the US Scientific Registry of Transplant Recipients between February 28, 2002, and March 31, 2003. Transplant recipients (N = 4798) had end-stage liver disease and received DD livers. Main outcome measures: MELD score distribution (range, 6,40), graft survival, and patient survival for liver transplant recipients in small (<100) and large (> or =100 on the waiting list) OPOs. RESULTS: The distribution of MELD scores was the same in large and small OPOs; 92% had a MELD score of 18 or less, 7% had a MELD score between 19 and 24, and only 2% of listed patients had a MELD score higher than 24 (P = .85). The proportion of patients receiving transplants in small OPOs and with a MELD score higher than 24 was significantly lower than that in large OPOs (19% vs 49%; P<.001). Patient survival rates at 1 year after transplantation for small OPOs (86.4%) and large OPOs (86.6%) were not statistically different (P = .59), and neither were graft survival rates in small OPOs (80.1%) and large OPOs (81.3%) (P = .80). Conclusions: There is a significant disparity in MELD scores in liver transplant recipients in small vs large OPOs; fewer transplant recipients in small OPOs have severe liver disease (MELD score >24). This disparity does not reflect the stated goals of the current allocation policy, which is to distribute livers according to a patient's medical need, with less emphasis on keeping organs in the local procurement area. (JAMA 2004;291:1871,1874.) [source] De novo breast cancer in patients with liver transplantation: University of Pittsburgh's experience and review of the literatureLIVER TRANSPLANTATION, Issue 1 2004M.Tahir Oruc De novo malignancies are one of the current problems in patients with organ transplantation. The incidence has been considered to be higher as a result of increases of oncogenic viruses in immunosuppressed organ recipients. Published reports have shown increased incidence of de novo tumors such as malignant lymphomas and cutaneous neoplasms but decreased incidence of breast cancer. A variety of factors affect de novo breast cancer development in organ recipients, including immunosuppression, viruses, and underlying disease. The aims of this review are to evaluate the incidence and management of patients with de novo breast cancer by giving the University of Pittsburgh's data, and to evaluate the incidence of de novo breast cancer in published reports in light of an age-adjusted rate. According to age-adjusted rates presented by the National Cancer Institute's Surveillance, Epidemiology and End Results data, we found increased incidence rate of de novo breast cancer in the previously published series. The University of Pittsburgh's incidence rate of de novo breast cancer was determined in a fashion similar to that for the Surveillance, Epidemiology and End Results data. Eighty-three percent of all patients were diagnosed at early stages, and it appeared to take longer for de novo breast cancer to develop in patients treated with tacrolimus than in patients treated with cyclosporine. In conclusion, surgical treatment of breast cancer in liver recipients is the same as treatment of breast cancer in patients without transplantation. However, the effects of chemotherapy, radiotherapy, and/or tamoxifen remain unclear in transplanted patients and need to be evaluated in larger studies. (Liver Transpl 2004;10:1,6.) [source] Late hepatic allograft dysfunctionLIVER TRANSPLANTATION, Issue 11B 2001Professor of Medicine Russell H. Wiesner MD Key Points 1Lifelong monitoring of graft function, immunosuppressive levels, and screening for drug toxicity is required in all liver recipients. 2Late hepatic allograft dysfunction is common and is caused by a variety of etiologies including rejection, infection, biliary/vascular abnormalities, recurrence of disease, and drug hepatotoxicity. 3In all patients with late hepatic allograft dysfunction, liver biopsy should be performed to assess for the presence of rejection, and to thus avoid excessive use of bolus corticosteroid therapy and guide appropriate immunosuppressive management. 4Recurrence of disease is the most common cause of late hepatic allograft dysfunction. 5Hepatitis C universally reinfects the hepatic allograft, and is associated with decreased patient and graft survival and leads to the recurrence of cirrhosis in 28% of patients within 5 years of transplantation. 6Major advances have been made in preventing recurrence of hepatitis B by the use of hepatitis B immune globulin in combination with lamivudine therapy. 7Autoimmune liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis have a recurrence rate of approximately 20% to 30%. 8In patients developing recurrence of autoimmune hepatitis, steroid withdrawal is the most common cause. 9Recurrent hepatocellular cancer can be markedly reduced if strict guidelines are adhered to in selecting patients. 10Drug hepatotoxicity must always be considered in the differential diagnosis of late hepatic allograft dysfunction. [source] Transplantation of three adult patients with one cadaveric graft: Wait or innovateLIVER TRANSPLANTATION, Issue 2 2000Daniel Azoulay Graft shortage continues to prolong waiting times for adults requiring liver transplantation. Living related donor transplantation is possible for only a small minority of adults. The techniques for in situ splitting of the liver used for right and left hepatectomies in living donors were adapted to a combined split-liver,domino procedure to obtain right and left hemiliver grafts from a patient undergoing total hepatectomy with liver transplantation for a metabolic disorder. The two grafts were adequate in size and function for transplantation to two adults with low priority for regular cadaver grafts. More frequent use of split-liver techniques in cadaver donors could considerably reduce the graft shortage and waiting time for adult liver recipients. [source] Post-transplant lymphoproliferative disorder after pediatric liver transplantation: Characteristics and outcomePEDIATRIC TRANSPLANTATION, Issue 3 2009María C. Fernández Abstract:,Purpose:, Post-Transplant Lymphoproliferative Disorder (PTLD) is a life threatening complication in organ transplant recipients. Risk factors include primary Epstein-Barr virus infection, intensity of immunosupression and cytomegalovirus infection. Objectives:, To evaluate the incidence, clinical presentation, risk factors, histopathologic appearance and outcome of pediatric liver recipients with PTLD at our institution. Method:, Retrospective, descriptive and observational analysis. Between November 1992 and December 2005, 383 liver transplants were performed. The diagnosis of PTLD was based on clinical history and physical examination and confirmed by histologic appearance and immunohistologic staining. Knowles' classification was used for histopathologic diagnosis. Results:, The incidence of PTLD was 5.7% (n: 22p). The average onset after tansplantation (OLT) was 24.9 months. Clinical manifestations were malaise, anorexia, fever of more than 3 days, peripheral adenopathy, tonsillar hypertrophy, abdominal mass, hepatosplenomegaly, snoring, interstitial pulmonary infiltrate, G.T.-tract bleeding, rash, submaxilar mass. Histopathologic diagnosis were Plasmocytic Hyperplasia (n: 10), Polymorphic Lymphoproliferative Disorder (n: 8), Non-Hodgkin Lymphoma (n: 4). Mortality was 18%. Conclusion:, The clinical presentations were protean and not specific. A high index of suspicion is important for early diagnosis as it correlates with more benign lesions and more favorable outcume. The lower mortality rate in our series is concordant with that reported in more recent articles. [source] Solid Organ Transplantation in AL AmyloidosisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010P. T. Sattianayagam Vital organ failure remains common in AL amyloidosis. Solid organ transplantation is contentious because of the multisystem nature of this disease and risk of recurrence in the graft. We report outcome among all AL patients evaluated at the UK National Amyloidosis Centre who received solid organ transplants between 1984 and 2009. Renal, cardiac and liver transplants were performed in 22, 14 and 9 patients respectively, representing <2% of all AL patients assessed during the period. One and 5-year patient survival was 95% and 67% among kidney recipients, 86% and 45% among heart recipients and 33% and 22% among liver recipients. No renal graft failed due to recurrent amyloid during median (range) follow up of 4.8 (0.2,13.3) years. Median patient survival was 9.7 years among 8/14 cardiac transplant recipients who underwent subsequent stem cell transplantation (SCT) and 3.4 years in six patients who did not undergo SCT (p = 0.01). Amyloid was widespread in all liver transplant recipients. Solid organ transplantation has rarely been performed in AL amyloidosis, but these findings demonstrate feasibility and support a role in selected patients. [source] Recurrence-Free Long-Term Survival After Liver Transplantation in Patients with 18F-FDG Non-Avid Hilar Cholangiocarcinoma on PETAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009A. Kornberg The aim of this retrospective study was to assess the value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for predicting biological tumor behavior and outcome after liver transplantation (LT) in patients with otherwise unresectable hilar cholangiocarcinoma (HC). Preoperative 18F-FDG-PET scanning was performed in 13 patients with type IV Klatskin tumor before LT. PET+ status indicated patients with an increased pretransplant 18F-FDG uptake, whereas PET, recipients had no increased preoperative 18F-FDG uptake on PET. Pretransplant PET findings were correlated with histopathological tumor characteristics and patient outcome after LT. Eight patients demonstrated positive preoperative PET findings (61.5%), whereas five patients had no increased preoperative 18F-FDG tumor uptake (38.5%) on PET. One PET+ patient died after 1 month due to liver allograft dysfunction. Seven PET+ liver recipients developed tumor recurrence, whereas five PET, patients were tumor-free alive after a median of 76 months post-LT (p = 0.001). The 2-year recurrence-free survival rate after LT was 100% in PET, patients and 28.6% in the PET+ population (log-rank = 0.008). Our results suggest that patients with 18F-FDG non-avid HC on PET may achieve recurrence-free long-term survival after LT. [source] Increased Expression of Regulatory Tr1 Cells in Recurrent Hepatitis C after Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009A. Carpentier Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the main reason for liver transplantation. However, 80% of transplanted patients present an accelerated recurrence of the disease. This study assessed the involvement of regulatory T-cell subsets (CD4+CD25+ cells: ,Treg' and CD49b+CD18+ cells: ,T regulatory-1' cells), in the recurrence of HCV after liver transplantation, using transcriptomic analysis, ELISA assays on serum samples and immunohistochemistry on liver biopsies from liver recipients 1 and 5 years after transplantation. Three groups of patients were included: stable HCV-negative recipients and those with mild and severe hepatitis C recurrence. At 5 years, Treg markers were overexpressed in all HCV+ recipients. By contrast, Tr1 markers were only overexpressed in patients with severe recurrence. At 1 year, a trend toward the overexpression of Tr1 was noted in patients evolving toward severe recurrence. IL-10 production, a characteristic of the Tr1 subset, was enhanced in severe recurrence at both 1 and 5 years. These results suggest that Tr1 are enhanced during severe HCV recurrence after liver transplantation and could be predictive of HCV recurrence. High levels of IL-10 at 1 year could be predictive of severe recurrence, and high IL-10 producers might warrant more intensive management. [source] Incidence Rate and Outcome of Gram-Negative Bloodstream Infection in Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009M. N. Al-Hasan Bacterial infections are common complications of solid organ transplantation (SOT). In this study, we defined the incidence, mortality and in vitro antimicrobial resistance rates of Gram-negative bloodstream infection (BSI) in SOT recipients. We identified 223 patients who developed Gram-negative BSI among a cohort of 3367 SOT recipients who were prospectively followed at the Mayo Clinic (Rochester, MN) from January 1, 1996 to December 31, 2007. The highest incidence rate (IR) of Gram-negative BSI was observed within the first month following SOT (210.3/1000 person-years [95% confidence interval (CI): 159.3,268.3]), with a sharp decline to 25.7 (95% CI: 20.1,32.1) and 8.2 (95% CI: 6.7,10.0) per 1000 person-years between 2 and 12 months and more than 12 months following SOT, respectively. Kidney recipients were more likely to develop Gram-negative BSI after 12 months following transplantation than were liver recipients (10.3 [95% CI: 7.9,13.1] vs. 5.2 [95% CI: 3.1,7.8] per 1000 person-years). The overall unadjusted 28-day all-cause mortality of Gram-negative BSI was 4.9% and was lower in kidney than in liver recipients (1.6% vs. 13.2%, p < 0.001). We observed a linear trend of increasing resistance among Escherichia coli isolates to fluoroquinolone antibiotics from 0% to 44% (p = 0.002) throughout the study period. This increase in antimicrobial resistance may influence the choice of empiric therapy. [source] Impaired Bone Health in Adolescents After Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2008H. Valta Long-term complications related to immunosuppressive medication are an important problem after liver transplantation (OLT). This study was carried out to evaluate the bone health and risk factors for osteoporosis and fractures in 40 pediatric liver transplant recipients. The results of 208 longitudinal bone mineral density (BMD) measurements were analyzed retrospectively. In addition, a dual-energy X-ray absorptiometry was performed to assess the bone mineral content more precisely and to detect subclinical vertebral fractures (VF). The median age of the patients was 14 years and mean postoperative follow-up 7.0 years. The results showed that over half (58%) had lumbar spine (LS) Z-score ,,1.0 and one-fifth (18%) had asymptomatic VF. LS Z-score tended to increase from the first year after OLT, but during puberty the bone mass gain was suboptimal and Z-scores decreased in some subjects. Patients with VF were older at the time of OLT (p = 0.002) and their LS Z-score was lower (p = 0.001). Children transplanted before 10 years of age had less VF (p = 0.004) and higher LS Z-score (p = 0.005) than older patients. In conclusion, adolescent liver recipients are prone to osteoporosis and prevention should be targeted especially to this age group. [source] Adenovirus Infection in Pediatric Liver and Intestinal Transplant Recipients: Utility of DNA Detection by PCRAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2003Gwenn E. McLaughlin To evaluate the incidence of adenovirus (AdV) infection in pediatric liver and intestinal transplant recipients, the records of patients with possible AdV infection were reviewed for demographic data, symptomatology, methods of diagnosis, treatment and outcome. To evaluate the impact of polymerase chain reaction (PCR) amplification and identification of AdV DNA as a diagnostic test, the incidence and outcome of AdV before and after the introduction of PCR were compared. Adenovirus infection was identified in 4.1% of liver recipients and 20.8% of intestinal transplant recipients. The overall incidence of AdV did not increase over time, even following the introduction of PCR for virus detection. The higher incidence of AdV in the pediatric intestinal transplant recipients may be attributed to the frequent application of PCR methodology to intestinal biopsy material. Detection of AdV by PCR was associated with reduced mortality compared with detection by culture, either because of earlier detection of invasive disease or because PCR detects the presence of latent as well as active AdV. [source] Indocyanine green elimination but not bilirubin indicates improvement of graft function during MARS therapyCLINICAL TRANSPLANTATION, Issue 6 2007Stefan Scheingraber Abstract:, Measurement of indocyanine green plasma disappearance rate (PDRICG) has been suggested as a meaningful liver function parameter. However, there are only very limited data concerning its value in the monitoring of graft dysfunction (GDF) and primary non-function (PNF) especially during molecular absorbent recirculating system (MARS) therapy. This study was therefore performed to evaluate the diagnostic accuracy to detect and monitor GDF with the measurement of the PDRICG in direct comparison with conventional markers like bilirubin and prothrombin time (PT). Of the 19 liver recipients, four patients with GDF and two patients with PNF were treated with 38 MARS cycles. Only PDRICG did reliably indicate liver function between patients with GDF/PNF and patients with sufficient graft function who served as controls. Moreover, receiver operating characteristic analysis showed the highest areas under the curve (AUC) for PDRICG (AUCPDRICG max: 0.840, AUCPDRICG max: 0.822), followed by bilirubin (AUCbilirubin: 0.528) and PT (AUCPT: 0.546). In contrast to the decrease of the serum bilirubin concentration due to MARS, a noticeable improvement of PDRICG was evident only in patients with GDF. Patients with acute fulminant failure and PNF had significantly lower PDRICG values, which did not improve even during continuous MARS treatments. Conclusively, monitoring of PDRICG is superior to bilirubin and PT measurements to determine the graft function especially in patients with PNF and GDF undergoing MARS therapy. [source] Optimal prophylactic dosage and disposition of micafungin in living donor liver recipientsCLINICAL TRANSPLANTATION, Issue 6 2004Satoshi Kishino Abstract:, Micafungin, a new candin antifungal drug, has a good safety profile and a significant therapeutic effect against Candida and Aspergillus. Little is known, however, about the optimal prophylactic dosage and the disposition of micafungin in liver transplant recipients, or about the effect of continuous venovenous hemodialysis (CVVH) on the pharmacokinetics of micafungin. Six living donor liver transplant patients were enrolled in this study. The mean Cmax and Cmin (trough) values of micafungin in plasma were 6.31 ± 1.08 and 1.65 ± 0.54 ,g/mL, respectively. The mean elimination half-life (t1/2) and mean area under the curve up to 12 h post-dosing (AUC 0,12 h) were 13.63 ± 2.77 h and 50.04 ± 6.48 ,g·h/mL, respectively. The concentrations of micafungin at the inlet and outlet of the dialyzer were very similar. The mean (±SD) ratio of micafungin concentrations at the inlet and outlet of the dialyzer (coutlet/cinlet) and the clearance of micafungin were 0.96 ± 0.04 and 0.054 ± 0.04 mL/min/kg, respectively. The amount in the ultrafiltrate was 1.0 mg. Micafungin effectively prevents systemic fungal infection in patients who have undergone liver transplantation. No significant differences were observed in the disposition of micafungin in recipients, and the therapeutic drug level can be achieved by administration of micafungin at a dosage of 40,50 mg/d. The CVVH had little effect on micafungin kinetics, and no dose adjustment or modification of dosing interval was needed during CVVH. [source] Use of lidocaine metabolism to test liver function during the long-term follow-up of liver transplant recipientsCLINICAL TRANSPLANTATION, Issue 3 2004Filoména Conti Abstract:, Background/Aims:, The aim of this study was to assess the usefulness of the monoethylglycinexylidide (MEGX) test to monitoring the long-term function of liver allografts. Methods:, MEGX production was measured prospectively in 60 consecutive liver transplant recipients undergoing their annual review. Results:, Median MEGX values in liver recipients (54 ng/mL; range 10,146) were lower than those found in healthy controls (78 ng/mL; range 44,118). MEGX values correlated negatively with alanine aminotransferase (ALT) activity (p = 0.004) and with the overall histological score (p = 0.01), and positively with sulfobromophthalein (BSP) and indocyanine green (ICG) clearances (p = 0.0002 and p = 0.002, respectively). A stepwise decline was observed with worsening liver fibrosis, from 71 ± 5 ,g/L in patients with no fibrosis to 27 ± 9 ,g/L in patients with bridging fibrosis (p = 0.002). BSP and ICG clearances correlated more closely than the MEGX test with the overall histological score (p = 0.001 and p = 0.001, respectively) and portal fibrosis (p = 0.002 and p = 0.001). Conclusions:, The measurement of MEGX formation is a simple and non-invasive method to monitor liver graft function. It may constitute a valuable tool for assessing the degree of fibrosis. [source] | ||||||||||||||||||||||