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Transplant Setting (transplant + setting)
Selected AbstractsWorse recent efficacy of antiviral therapy in liver transplant recipients with recurrent hepatitis C: Impact of donor age and baseline cirrhosis,LIVER TRANSPLANTATION, Issue 7 2009Marina Berenguer We hypothesized that antiviral efficacy [sustained virologic response (SVR)] has improved in recent years in the transplant setting. Our aim was to assess whether the efficacy of pegylated interferon (PegIFN),ribavirin (Rbv) has improved over time. One hundred seven liver transplant patients [74% men, 55.5 years old (range: 37.5,69.5), 86% genotype 1a or 1b] were treated with PegIFN-Rbv for 355 (16,623) days at 20.1 (1.7,132.6) months after transplantation. Tacrolimus was used in 61%. Sixty-seven percent had baseline F3,F4 (cirrhosis: 20.5%). Donor age was 49 (12,78) years. SVR was achieved in 39 (36.5%) patients, with worse results achieved in recent years (2001,2003: n = 27, 46.5%; 2004: n = 23, 43.5%; 2005: n = 21, 35%; 2006 to January 2007: n = 36, 24%; P = 0.043). Variables associated with SVR in the univariate analysis included donor age, baseline viremia and cirrhosis, bilirubin levels, rapid virologic response and early virologic response (EVR), premature discontinuation of PegIFN or Rbv, and accumulated Rbv dose. In the multivariate analysis, the variables in the model were EVR [odds ratio (OR): 0.08, 95% confidence interval (CI): 0.016,0.414, P = 0.002] and donor age (OR: 1.039, 95% CI: 1.008,1.071, P = 0.01). Variables that had changed over time included donor age, baseline viremia, disease severity (cirrhosis, baseline bilirubin, and leukocyte and platelet counts), interval between transplantation and therapy, and use of growth factors. In the multivariate analysis, variables independently changing were donor age (OR: 1.041, 95% CI: 1.013,1.071, P = 0.004), duration from transplantation to antiviral therapy (OR: 1.001, 95% CI: 1.000,1.001, P = 0.013), and baseline leukocyte count (OR: 1.000, 95% CI: 1.000,1.000, P = 0.034). In conclusion, the efficacy of antiviral therapy with PegIFN-Rbv has worsened over time, at least in our center. The increase in donor age and greater proportion of patients treated at advanced stages of disease are potential causes. Liver Transpl 15:738,746, 2009. © 2009 AASLD. [source] How to diagnose and treat hepatitis B virus antiviral drug resistance in the liver transplant settingLIVER TRANSPLANTATION, Issue S2 2008Anna S. F. Lok Key Points 1Hepatitis B virus variants with antiviral drug,resistant mutations and/or hepatitis B immune globulin,resistant mutations are the main cause of hepatitis B virus reinfections post,liver transplant. 2Early diagnosis of antiviral drug resistance and prompt initiation of rescue therapy are important in preventing hepatitis flares and hepatic decompensation. 3Virologic breakthrough is the first indication of antiviral drug resistance. 4Genotypic resistance testing should be performed when possible to avoid unnecessary modification of treatment in patients who do not have confirmed antiviral drug resistance and to permit appropriate selection of rescue therapy in those who have confirmed antiviral drug resistance. 5Choice of rescue therapy requires knowledge of the past history of hepatitis B virus treatments and virologic response to those treatments, patterns of mutations detected at the time of virologic breakthrough, and in vitro cross-resistance data. 6Occurrence of antiviral drug resistance can be reduced by the use of the most potent nucleos(t)ide analogue(s) with the highest genetic barrier to resistance, emphasis of medication compliance, and close monitoring of virologic response. Liver Transpl 14:S8,S14, 2008. © 2008 AASLD. [source] Analysis of a successful HCV-specific CD8+ T cell response in patients with recurrent HCV-infection after orthotopic liver transplantation,,LIVER TRANSPLANTATION, Issue 12 2004Norbert Hubert Gruener Virus-specific CD8+ T cells play a major role in antiviral immune defenses; their significance in the transplant setting, however, is unclear. In the present study, we asked whether hepatitis C virus (HCV)-specific CD8+ T cells were detectable in the presence of an immunosuppressive treatment and whether the HCV-specific CD8+ T cell response correlates with treatment outcome in patients who receive interferon (IFN)-, / ribavirin therapy after orthotopic liver transplantation (OLTx). Liver- and blood-derived T cell lines of 21 patients after OLTx were studied before, at the end of, and after antiviral treatment. Virus-specific IFN-, production in response to a panel of previously identified HCV-specific epitopes restricted by the human leukocyte antigen (HLA) class I molecules A2, A3, B7, B35, and B44 of structural and nonstructural HCV protein was determined by enzyme-linked immunospot (ELISPOT) assay. Before treatment, only low numbers of HCV-specific CD8+ T cells were detectable. In 6 patients with a sustained virological response, a significant, multispecific, and sustained CD8+ T cell response was detectable, which was mainly found in the peripheral blood. Nonresponders and transient responders showed undetectable, weak, or transient HCV-specific CD8+ T cell responses. (Sustained responders vs. transient and nonresponders: Wilcoxon rank-signed test; P < .01). In conclusion, our data indicate that despite immunosuppression, HCV-specific CD8+ T cells are detectable in patients with recurrent HCV infection after OLTx and that a significant, multispecific, and long-lasting HCV-specific CD8+ T cell response contributes to viral elimination. (Liver Transpl 2004;10:1487,1496.) [source] Prevalence of Human Herpesvirus-6 Chromosomal Integration (CIHHV-6) in Italian Solid Organ and Allogeneic Stem Cell Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009L. Potenza The unique phenomenon of human herpesvirus-6 (HHV-6) chromosomal integration (CIHHV-6) may account for clinical drawbacks in transplant setting, being misinterpreted as active infection and leading to unnecessary and potentially harmful treatments. We have investigated the prevalence of CIHHV-6 in 205 consecutive solid organ (SO) and allogeneic stem cell transplant (alloSCT) Italian patients. Fifty-two (38.5%) of 135 solid organ transplant (SOT) and 16 (22.8%) of 70 alloSCT patients resulted positive for plasma HHV-6 DNA by real-time polymerase chain reaction. Seven SOT and three alloSCT patients presented HHV-6-related diseases, requiring antivirals. Two further patients (0.9%) were identified, presenting high HHV-6 loads. The quantification of HHV-6 on hair follicles disclosed the integrated state, allowing the discontinuation of antivirals. Before starting specific treatments, CIHHV-6 should be excluded in transplant patients with HHV-6 viremia by the comparison of HHV-6 loads on different fluids and tissues. Pretransplantation screening of donors and recipients may further prevent the misdiagnosis of CIHHV-6. [source] Human herpesviruses-6, -7 and -8 in organ transplant recipientsCLINICAL MICROBIOLOGY AND INFECTION, Issue 9 2000N. Singh The newer herpesviruses are being increasingly recognized as significant opportunistic pathogens in organ transplant recipients. Published data support the role of human herpesvirus-6 as a potential cause of encephalitis and bone marrow suppression in transplant setting. An association of human herpesvirus-6 with fungal infections and cytomegalovirus infection has also been documented. Human herpesvirus-7 also appears to be an immunomodulatory agent and may facilitate the pathogenicity of cytomegalovirus. Unlike human herpesviruses -6 and -7, human herepsvirus -8 is not ubiquitous; its seroprevalence exhibits wide geographic variation. Human herpesvirus-8 has been causally associated with post-transplant Kaposi's sarcoma. The complete spectrum of pathogenicity and ultimately the effective prophylaxis and management of these viruses has yet to be fully elucidated. [source] The dual role of Fas-ligand as an injury effector and defense strategy in diabetes and islet transplantation,BIOESSAYS, Issue 2 2006Michal Pearl-Yafe The exact process that leads to the eruption of autoimmune reactions against , cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of , cell injury is controversial and points to possibly important roles for the perforin,granzyme, Fas,Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of , cells to FasL-mediated apoptosis, the conditions that underlie this , cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of ,-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211,222, 2006. © 2006 Wiley periodicals, Inc. [source] | ||||||||||