Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation.

Background: Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients.

Methods: Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected.

IL-33-mediated IL-13 secretion by ST2+ Tregs controls inflammation after lung injury.

Acute respiratory distress syndrome is an often fatal disease that develops after acute lung injury and trauma. How released tissue damage signals, or alarmins, orchestrate early inflammatory events is poorly understood. Herein we reveal that IL-33, an alarmin sequestered in the lung epithelium, is required to limit inflammation after injury due to an unappreciated capacity to mediate Foxp3+ Treg control of local cytokines and myeloid populations.

Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers in Liver Transplant Recipients.

Biomarker profiles of acute rejection in liver transplant recipients could enhance the diagnosis and management of recipients. Our aim was to identify diagnostic proteoform signatures of acute rejection in circulating immune cells, using an emergent "top-down" proteomics methodology. We prepared differentially processed and cryopreserved cell lysates from 26 nonviral liver transplant recipients by molecular weight-based fractionation and analyzed them by mass spectrometry of whole proteins in three steps: (i) Nanocapillary liquid chromatography coupled with high-resolution tandem mass spectrometry; (ii) database searching to identify and characterize intact proteoforms; (iii) data processing through a hierarchical linear model matching the study design to quantify proteoform fold changes in patients with rejection versus normal liver function versus acute dysfunction without rejection.

Fibroinflammatory biliary stricture: a rare bile duct lesion masquerading as cholangiocarcinoma.

Introduction: Fibroinflammatory biliary stricture (FIBS) is a rare benign tumor-like process of the extrahepatic bile duct that masquerades as cholangiocarcinoma.

Methods: In order to distinguish this unusual entity from cancer, we performed a systematic analysis of 11 patients with FIBS. All patients presented with jaundice; six patients had coexisting autoimmune disease.

Posttransplant lymphoproliferative disorders in liver transplantation: a 20-year experience.

Objective: To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution.

Summary Background Data: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms.

A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients: an interim report.

Background: Tacrolimus (Tac) and mycophenolate mofetil (MMF) are newly approved immunosuppressive agents. However, the safety and efficacy of the combination of MMF and Tac in primary liver transplantation has not been determined.

Methods: An Institutional Review Board-approved, open-label prospective randomized protocol was initiated to study the efficacy and toxicity of Tac and steroids (double-drug therapy) versus Tac, steroids, and MMF (triple-drug therapy) in primary adult liver transplant recipients.

Clinical intestinal transplantation: new perspectives and immunologic considerations.

Background: Although tacrolimus-based immunosuppression has made intestinal transplantation feasible, the risk of the requisite chronic high-dose treatment has inhibited the widespread use of these procedures. We have examined our 1990-1997 experience to determine whether immunomodulatory strategies to improve outlook could be added to drug treatment.

Study Design: Ninety-eight consecutive patients (59 children, 39 adults) with a panoply of indications received 104 allografts under tacrolimus-based immunosuppression: intestine only (n = 37); liver and intestine (n = 50); or multivisceral (n = 17).

In vitro culture of B-lymphocytes derived from Epstein-Barr-virus-associated posttransplant lymphoproliferative disease: cytokine production and effect of interferon-alpha.

Epstein-Barr-virus-associated posttransplant lymphoproliferative disease ranges from transient lymphadenitis to aggressive lymphoma. This study characterizes an in vitro model to study the pathogenesis of this disease with a cell culture system. Five B-cell lines derived from posttransplant lymphoproliferative disease tissue were characterized with regard to immunophenotype, karyotype, molecular genetics, cytokine production, and growth regulation.

Survival and quality of life after liver transplantation for acute alcoholic hepatitis.

The applicability of liver transplantation for ALD remains limited because of ethical arguments and also because of the perception of poor outcome after transplantation. Patients with alcoholic cirrhosis are known to do as well as patients with nonalcoholic liver disease after receiving liver allografts; however, the outcome in patients with severe acute alcoholic hepatitis in this setting is unclear. We studied 9 liver transplant recipients in whom severe acute alcoholic hepatitis was retrospectively diagnosed; 8 had underlying cirrhosis, and 1 had advanced fibrosis.

Immune status of recipients following bone marrow-augmented solid organ transplantation.

It has been postulated that the resident "passenger" leukocytes of hematolymphoid origin that migrate from whole organ grafts and subsequently establish systemic chimerism are essential for graft acceptance and the induction of donor-specific nonreactivity. This phenomenon was augmented by infusing 3 x 10(8) unmodified donor bone-marrow cells into 40 patients at the time of organ transplantation. Fifteen of the first 18 analyzable patients had sequential immunological evaluation over postoperative intervals of 5 to 17 months, (which included 7 kidney (two with islets), 7 liver (one with islets), and one heart recipient).

The current status of hepatic transplantation at the University of Pittsburgh.

Tacrolimus is a more potent and satisfactory immunosuppressant than CyA for combination therapy with prednisone. In randomized trials comparing the 2 drugs, the ability of tacrolimus to rescue intractably rejecting grafts on the competing CyA arm allowed equalization of patient and graft survival on both arms when the intent-to-treat analytic methodology was applied. The ability of tacrolimus to systematically rescue the treatment failures of CyA suggested, as a matter of common sense, that it is the preferred baseline drug for hepatic transplantation.

Interleukin-10 production by a B-cell line derived from human post-transplant lymphoproliferative disease.

Interleukin-10 (IL-10) is a cytokine known to regulate growth and differentiation in activated human B cells. We studied IL-10 production in a B-cell line derived from Epstein-Barr virus associated post-transplant lymphoproliferative disease (PTLD). Reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated IL-10 mRNA within the cells.

Allografts surviving for 26 to 29 years following living-related kidney transplantation: analysis by light microscopy, in situ hybridization for the Y chromosome, and anti-HLA antibodies.

We studied seven patients aged 14 to 40 years who received living-related kidney transplants and had allograft survivals of 26 to 29 years. The blood urea and creatinine were either within normal limits or marginally elevated. Histopathologic examination showed only mild mesangial expansion, interstitial fibrosis, and arteriosclerosis.

EBER gene expression in Epstein-Barr virus-associated hematopoietic neoplasms.

Epstein-Barr virus encoded RNA's (EBER) are small RNA species found in cells latently infected by the virus. The physiological function of these molecules is currently a matter of speculation. Nonetheless, their presence in extremely high copy number has made it possible to reliably detect the Epstein-Barr virus by in-situ hybridization, in human tissues routinely fixed with formalin and embedded in paraffin.

Acceleration of chronic failure of intrahepatic canine islet autografts by a short course of prednisone.

A topic of current interest in islet transplantation is the selection of an optimal site for long-term graft survival since the intrahepatic site may be characterized by long-term failure. Additionally, the use of immunosuppressive agents such as prednisone may adversely affect long-term graft function. In this study, we examined the long-term outcome of intrahepatic canine islet autografts and compared this with results obtained in animals treated with a short-term course of steroids or steroids plus insulin.

Hepatic transplantation at the University of Pittsburgh: new horizons and paradigms after 30 years of experience.

In the 1993 edition of this book, we described 4 major initiatives in liver transplantation: First, the evaluation of the new immunosuppressive drug FK506 (tacrolimus); second, the feasibility of combined liver-intestinal and multivisceral transplantation; third, 2 clinical attempts at hepatic xenotransplantation; and fourth, beginning attempts to enhance donor-specific nonreactivity with adjuvant bone marrow infusion. These and other new clinical studies during the last 12 months are the concerns of this update. The topics will be considered separately because of the unique design of each and the heterogeneity of the enrolled patient population.