Edson Abdala

Cytomegalovirus infection in transplant recipients

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.

Bacterial translocation during liver transplantation: A randomized trial comparing conventional with venovenous bypass vs. piggyback methods

The aim of this study was to evaluate the bacterial translocation in liver transplantation (LT), comparing the conventional and the piggyback methods. A total of 32 patients were randomized into the 2 groups. Samples of blood were collected from the radial artery, portal vein (PV) and hepatic vein (HV), in up to 120 minutes postreperfusion. The samples were sent for endotoxin level, as well as samples up to 2 minutes post‐perfusion were sent to culture. Hepatic artery and PV blood flows were measured at postreperfusion collection times. The results analyzed were: endotoxin concentration, its quantity, and hepatic clearance. The statistical treatment consisted of analyzing each groups mean profile. The analysis for endotoxin concentration in the radial artery was the deviation related to presurgery measure, and in the PV the deviation related to preclamping (PC) measure. The overall mean level of endotoxin concentration was 0.99 EU/mL in the artery, 1.30 EU/mL in the PV, and 1.22 EU/mL in the HV. The deviation was significant in the portal (P = 0.0031), but not in the artery samples (P = 0.2092). We detected a significant quantity of endotoxin in the artery and in the portal and the HVs (P < 0.001). There was no difference between the 2 groups and no hepatic clearance of endotoxin was detected either (P = 0.1515). All the cultures were negative. In conclusion, the study detected a significant translocation of endotoxin, but not of bacteria. The study also detected the absence of endotoxin hepatic clearance in both the piggyback and the conventional methods without any difference between them. Liver Transpl 13:488–496, 2007.

Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins

Treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae infections (KPC-EI) remains a challenge. Combined therapy has been proposed as the best choice, but there are no clear data showing which combination therapy is superior. Our aim was to evaluate the effectiveness of antimicrobial regimens for treating KPC-EI. This was a retrospective cohort study of KPC-EI nosocomial infections (based on CDC criteria) between October 2009 and June 2013 at three tertiary Brazilian hospitals. The primary outcomes were the 30-day mortality for all infections and the 30-day mortality for patients with bacteraemia. Risk factors for mortality were evaluated by comparing clinical variables of survivors and nonsurvivors. In this study, 118 patients were included, of whom 78 had bacteraemia. Catheter-related bloodstream infections were the most frequent (43%), followed by urinary tract infections (n = 27, 23%). Monotherapy was used in 57 patients and combined treatment in 61 patients. The most common therapeutic combination was polymyxin plus carbapenem 20 (33%). Multivariate analysis for all infections (n = 118) and for bacteremic infections (n = 78) revealed that renal failure at the end of treatment, use of polymyxin and older age were prognostic factors for mortality. In conclusion, polymyxins showed suboptimal efficacy and combination therapy was not superior to monotherapy.

Immunogenicity and reactogenicity of 2009 influenza A (H1N1) inactivated monovalent non-adjuvanted vaccine in elderly and immunocompromised patients.

Background Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them. Methods This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination. Results 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included. The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events. Conclusions The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)

Liver transplant from Anti-HBc-positive, HBsAg-negative donor into HBsAg-negative recipient: is it safe? A systematic review of the literature.

Avelino‐Silva VI, D′Albuquerque LAC, Bonazzi PR, Song ATW, Miraglia JL, de Brito Neves A, Abdala E. Liver transplant from Anti‐HBc‐positive, HBsAg‐negative donor into HBsAg‐negative recipient: is it safe? A systematic review of the literature. 
Clin Transplant 2010: 24: 735–746.

Liver transplantation: fifty years of experience.

Since 1963, when the first human liver transplantation (LT) was performed by Thomas Starzl, the world has witnessed 50 years of development in surgical techniques, immunosuppression, organ allocation, donor selection, and the indications and contraindications for LT. This has led to the mainstream, well-established procedure that has saved innumerable lives worldwide. Today, there are hundreds of liver transplant centres in over 80 countries. This review aims to describe the main aspects of LT regarding the progressive changes that have occurred over the years. We herein review historical aspects since the first experimental studies and the first attempts at human transplantation. We also provide an overview of immunosuppressive agents and their potential side effects, the evolution of the indications and contraindications of LT, the evolution of survival according to different time periods, and the evolution of methods of organ allocation.

Trichosporon asahii fatal infection in a non‐neutropenic patient after orthotopic liver transplantation

Abstract: Trichosporon asahii is a yeast that may cause systemic infection, especially in neutropenic patients. To our knowledge, only two cases of invasive infection with Trichosporon were previously described in liver transplant recipients. We describe an additional case of T. asahii infection after orthotopic liver transplantation in a non‐neutropenic patient who had no known risk factor for invasive fungal infection, and died in spite of amphotericin B therapy.

Surgical site infections in liver transplant recipients in the model for end-stage liver disease era: an analysis of the epidemiology, risk factors, and outcomes.

In recipients of liver transplantation (LT), surgical site infection (SSIs) are among the most common types of infection occurring in the first 60 days after LT. In 2007, the Model for End‐Stage Liver Disease (MELD) scoring system was adopted as the basis for prioritizing organ allocation. Patients with higher MELD scores are at higher risk for developing SSIs as well as other health care–associated infections. However, there have been no studies comparing the incidence of SSIs in the pre‐MELD era with the incidence in the period since its adoption. Therefore, the objectives of this study were to evaluate the incidence, etiology, epidemiology, and outcomes of post‐LT SSIs in those 2 periods and to identify risk factors for SSIs. We evaluated all patients who underwent LT over a 10‐year period (2002‐2011). SSI cases were identified through active surveillance. The primary outcome measure was an SSI during the first 60 days after LT. Risk factors were analyzed via logistic regression, and 60‐day survival rates were evaluated via Cox regression. We evaluated 543 patients who underwent LT 597 times. The SSI rates in the 2002‐2006 and 2007‐2011 periods were 30% and 24%, respectively (P = 0.21). We identified the following risk factors for SSIs: retransplantation, the transfusion of more than 2 U of blood during LT, dialysis, cold ischemia for >400 minutes, and a cytomegalovirus infection. The overall 60‐day survival rate was 79%. Risk factors for 60‐day mortality were retransplantation, dialysis, and a longer surgical time. The use of the MELD score modified the incidence and epidemiology of SSIs only during the first year after its adoption. Risks for SSIs were related more to intraoperative conditions and intercurrences after LT than to a patients status before LT. Liver Transpl 19:1011–1019, 2013.

Double-dose hepatitis B vaccination in cirrhotic patients on a liver transplant waiting list

Development of immunity to hepatitis B virus in cirrhotic patients waiting for liver transplantation is highly desirable. Though a double-dose regimen is available, little is know about its effectiveness. We examined the efficacy of double-dose hepatitis B virus vaccination in cirrhotic patients waiting for liver transplantation. We studied 43 patients who were waiting for liver transplantation. They were vaccinated with three doses of 40 mg hepatitis B vaccine at 0, 1 and 6 months; the normal dose is 20 microg. Efficacy was measured based on seroconversion of anti-HBs. Global response to the primary vaccination scheme was 67.5% (29 patients). Forty-one per cent of responders had anti-HBs titers above 1,000 IU/mL. No factors were associated with response, based on multivariate analysis. The vaccination scheme of 40 microg at 0, 1 and 6 months was superior to conventional vaccination doses (20 microg) for cirrhotic patients on a waiting list for liver transplantation.

Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial*

Objective: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. Design: Single center, randomized, double-blind controlled trial. Setting: Teaching hospital. Patients: Adult cancer patients with septic shock in the first 6 hours of ICU admission. Interventions: Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. Measurements and Main Results: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0–3] vs 0 [0–2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53–1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53–0.97; p = 0.03). Conclusions: We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.