International Journal of Organ Transplantation Medicine
Volume:4 Issue: 2, Spring 2013

Improvements in surgical techniques, immunosuppression, and post-transplantation patient care have led to the optimization of liver transplantation outcomes. However, the waiting list for liver transplantation is increasing at a greater pace. The large gap between the growing pool of patients waiting for liver transplantation and the scarcity of donor organs has fueled efforts to maximize existing donors and identify new sources.This article will be focused on the current state of liver transplantation using grafts from extended criteria donors (elderly donors, steatotic donors, donors with malignancies, donors with viral hepatitis) and from donation after cardiac death (DCD), as well as the use of partial grafts (split grafts and living-donor liver transplantation) and other suboptimal donors (donors with hypernatremia, infections, hypotension and inotropic support). Overall, broadened criteria for acceptable donor livers appear to lessen graft survival rates somewhat compared with rates for standard criteria organs.

Immunosuppression by biologic response modifiers (BRM) is a crucial component for successful organ transplantation. In addition to their variable effectiveness in the prevention of organ rejection, these medications have safety concerns that complicate therapeutic outcomes in organ transplant patients. This study aims at identifying and characterizing safety signals of serious adverse events associated with exposure to BRM among organ transplant patients in a real-world environment. The FDA Adverse Event Reporting System was utilized to apply a pharmacovigilance disproportionality analysis to indentify serious adverse events. Associations between drugs and events were measured by empirical Bayes geometric mean (EBGM) and the corresponding 95% confidence intervals (EB05–EB95). Associations with EBGM≥2 were considered significant safety signals. From 1997 to 2012, a total of 12,151 serious adverse event reports for BRM were reported; 15.6% of them (n=1,711) met the safety signal threshold of EB05>1, and 11.6% of these signals (n=199) were significant (EBGM≥2). Sirolimus and mycophenolate accounted for the majority of all signals; antithymocyte immunoglobulin (ATI) and cyclosporine contributed to the majority of significant signals. The following significant signals were identified for ATI (reduced therapeutic response, pulmonary edema, hypotension, serum sickness, infusion-related reaction, and anaphylactic reaction); for azathioprine (alternaria infection, fungal skin infection, and lymphoproliferative disorder); for cyclosporine (neurotoxicity, graft vs. host disease, and thyroid cancer); for cyclophosphamide (disease progression); for daclizumab (cytomegalovirus infection); and for tacrolimus (coma and tremor). 33.6% of these events contributed to patient death (n=67); 6.5% were life-threatening (n=13); 32.1% lead to hospitalization (n=64); and 27.6% resulted in other serious outcomes (n=55). Utilization of BRM for the prophylaxis against transplant rejection is associated with serious adverse events that could be fatal.

The growing gap between organ supply and demand remains a worldwide serious problem. Losing dead-brain donor organs can be attributed to several reasons including un-recognition of potential donor by ICU staff, death before official declaration of brain death and high refusal rate of deceased donors’ families. To study the trend of dead-brain patients’ relatives refusal of organ donation from 2007 to 2011. This study was a retrospective review of all patients who had been introduced as brain death to the organ procurement unit (OPU) of Iranian Tissue Bank between April 2007 and April 2012 according to preliminary neurological exam performed in the hospital of origin. The refusal rate of dead-brain patients’ families and its reasons was evaluated. A total of 874 ICU admitted patients with severe brain injury (Glasgow coma score <7) was introduced to our center and were visited by the coordinator team during April 2007 to April 2012. 412 (47%) patients were excluded from the study mainly due to unsuitability for donation according to the approved medical protocols (n=205) and not fulfilling the brain death criteria (n=66). The families of the remaining cases (n=462) had been interviewed 343 (74.2%) of whom permitted donation. The mean±SD age of donors was 29.8±13.2 years; the male/female ratio was almost 2. The most common reason of brain death was traffic collision (n=120; 56.3%) and cerebrovascular accidents (n=40; 18.8%). The refusal rate from 2007 to 2011 has decreased respectively, from 30.4% to 20% in Tehran, and from 57.1% to 51.6% in other cities. The overall refusal rate was 25.8%. Our study confirmed that more level of expertise of the coordinator team and continuous public education, would result in higher rate of consent to organ donation.

A growing body of evidence demonstrated an immune etiology as well as nonimmune mechanisms for episodes of clinical acute rejection and long-term allograft dysfunction. To investigate the correlation of IFN-γ-producing cells and TGF-β with incidence of clinical acute rejection in living-related and unrelated kidney allogarft recipients during the first post-transplant year. This multi-center study was performed on 57 kidney allograft recipients from living-related (n=20) and unrelated (n=37) donors between April 2011 and September 2012 and who were followed prospectively for a mean period of one year. Peripheral blood samples were collected from all patients pre-transplantation and at days 14, 30 and 90 after transplantation; PBMCs were used as responding cells in enzyme-linked immunosorbent spot (ELISPOT) assay to measure the frequency of IFN-γ-producing cells after stimulation with donor lymphocytes. Additionally, TGF-β levels were measured in cell culture supernatants of ELISPOT assay. During the follow-up period, 45 (79%) patients were diagnosed with stable graft function (group A); 12 (21%) experienced clinical acute rejection episodes (group B). The frequency of IFN-γ-producing cells was significantly (p<0.001) higher in the rejection group in all three times after transplantation. Also, post-transplantation comparison for TGF-β showed a significantly (p<0.001) higher contents in group A vs. group B. Comparing the post-transplantation levels of TGF-β and mean numbers of IFN-γ-producing cells between groups A and B demonstrated a continuous increment in TGF-β and decreasing frequencies of IFN-γ-producing cells in group A vs. group B. Serial post-transplantation monitoring of IFN-γ-producing donor reactive cells during the first months is a clinically feasible approach for identification of kidney allogarft recipients at risk for ongoing immune-mediated graft damage and later graft loss.

Transient bone marrow suppression, characterized by acute inability of the bone marrow to produce circulating blood cells, may strongly relate to the pathogenesis of some viral infections. To study the prevalence of some DNA and RNA viruses in patients with transient bone marrow suppression. EDTA-treated blood samples were collected from 27 patients with clinically- and laboratoryconfirmed transient bone marrow suppression. The genomic DNA of hepatitis B virus, adenovirus, polyomavirus BK, and parvovirus B19, and genomic RNA of hepatitis C and G viruses were extracted and amplified by sensitive and specific in-house simple and nested PCR and RT-PCR protocols, respectively. The risk factors that might be related to the studied viral infections were analyzed. Hepatitis B virus infection was diagnosed in 9 (33%) of 27 patients; adenovirus infection in 2 (7%); and parvovirus B19 infection in 7 (26%) of 27 patients. The genomic DNA of polyomovirus BK was not detected in any patients. Both hepatitis C and G viruses were found in 3 (11%) of 27 patients. Diagnosis of the high prevalence of hepatitis B virus, and parvovirus B19 in patients with transient bone marrow suppression, reflects the importance of these viral infections in introducing bone marrow suppression. This hypothesis should be confirmed in further studies.