E Mor

Hepatic artery thrombosis in pediatric liver transplantation: Graft salvage after thrombectomy

Abstract: Hepatic artery thrombosis (HAT) is a devastating complication that may occur after orthotopic liver transplantation (OLT). A higher incidence has been reported in children. Salvage of the graft by thrombectomy has been suggested as an alternative to re‐transplantation. In this study we report the outcome of three children who underwent thrombectomy for HAT. Between January 1992 and June 1998, 14 children (<u200317u2003yrs of age) underwent liver transplantation. Three developed HAT (one a whole‐liver graft recipient, age 17; two living‐related graft recipients, ages 4 and 4.5u2003yr). In the first patient, thrombosis of the hepatic artery was associated with scattered areas of parenchymal necrosis on computed tomography. In the two living‐related patients, HAT was found incidentally during re‐exploration for bleeding (day 2 andu2003dayu200310). Thrombectomy was performed in all three patients. At 18–24u2003months after thrombectomy, all three children had normal graft function. In the first patient, complete regeneration of the liver has been documented by computed tomography and a late asymptomatic recurrent thrombosis is suggested by absence of arterial flow on Doppler examination. The hepatic artery is patent in the two living‐related recipients. One of these living‐related recipients developed ischemic bile duct stricture and underwent successful percutaneous balloon dilatation. We conclude that long‐term normal graft function can be achieved by thrombectomy in pediatric liver recipients with HAT, even in the presence of limited parenchymal damage.

BK polyoma virus nephropathy in kidney transplant recipient: the role of new immunosuppressive agents.

BK POLYOMA virus (BKV) is a newly described agent causing renal dysfunction and failure among kidney transplant recipients. The virus remains latent following primary exposure at childhood and becomes activated in immunocompromised states. Clinically, the virus rarely causes symptoms such as hemorrhagic cystitis in bone marrow transplant recipients. Although viral shedding is detected in urine specimens of many renal transplant recipients, only a few will develop BKV transplant nephropathy. This disease process is characterized by a rapidly progressive loss of graft function. Introduction of new and more aggressive immunosuppressive protocols may explain the emergence of this new infectious complication. We describe our experience with 7 patients with BKV nephropathy with specific attention to possible risk factors.

Experience with lamivudine therapy for hepatitis B virus infection before and after liver transplantation, and review of the literature

Abstract.u2002 Ben‐Ari Z, Mor E, Tur‐Kaspa R (Beilinson Campus, Petah Tikva, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel). Experience with lamivudine therapy for hepatitis B virus infection before and after liver transplantation, and review of the literature. J Intern Med 2003; 253: 544–552.

The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation

Lapidus‐Krol E, Shapiro R, Amir J, Davidovits M, Steinberg R, Mor E, Avitzur Y. The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation.u2028Pediatr Transplantation 2010: 14:753–760.

New Immunosuppressive Agents for Maintenance Therapy in Organ Transplantation

SummaryTraditional cyclosporin-based immunosuppressive protocols are associated with relatively high incidences of early acute rejection and late graft loss due to chronic rejection. In addition, long-term immunosuppression with cyclosporin and corticosteroids has been associated with significant metabolic, infectious, malignant and cosmetic adverse effects. In the last decade, the goals of immunosuppression strategies have included not only short-term survival but also graft acceptance, with a low incidence of early acute rejection and minimal long-term toxicity.Tacrolimus and mycophenolate mofetil are 2 new immunosuppressive agents that have recently been approved for use. The mechanism of action and toxicity profile of tacrolimus are similar to that of cyclosporin. Tacrolimus reduces early acute rejection and is also effective in salvage of allografts with refractory rejection. A wide spectrum of adverse effects, including nephrotoxic, neurotoxic, gastrointestinal, metabolic and hematological effects, has been reported in association with tacrolimus but, unlike cyclosporin, this agent is not associated with hirsutism or gingival hyperplasia. Mycophenolate mofetil, an antimetabolite, has been effective in reducing early acute rejection and in treatment of refractory rejection when used in combination with cyclosporin instead of azathioprine. Its myelosuppressive and gastrointestinal toxicities are mild and reversible, but it may be associated with an increased risk of infections. Both agents permit early corticosteroid withdrawal.Other new immunosuppressive agents that act on different stages of the cell cycle but that have not yet been introduced for wide clinical use, including sirolimus (rapamycin), brequinar, mizoribine and gusperimus, are also discussed in this review

Combination hepatitis B immune globulin and lamivudine versus hepatitis B immune globulin monotherapy in preventing recurrent hepatitis B virus infection in liver transplant recipients.

UNTIL RECENTLY, liver transplantation in patients infected with the hepatitis B virus (HBV) was associated with a high rate of graft loss and poor survival because of viral recurrence. With the use of hepatitis B immune globulin (HBIG), allograft rejection rates have decreased (15% to 50%). However, recurrences still occur due to the saturation of the antibody-binding capacity of HBIG by the high viral load or by mutations in the hepatitis B surface antigen (HBsAg) molecule that render HBIG ineffective. Lamivudine, a purine nucleoside analog that serves as a reverse transcriptase inhibitor, is known to be a potent inhibitor of HBV replication. Lamivudine, administered before and after liver transplantation to prevent graft reinfection, was found to produce a complete and sustained suppression of viral replication. However, lamivudine escape mutations in the YMDD locus of the HBV DNA polymerase have been reported more frequently. Following 52 weeks of therapy post–liver transplantation, Perrillo et al documented a mutation rate of 27%. Our long-term study showed that 62.5% of patients developed lamivudine resistance. The aim of the present study was to determine the efficacy of the combination of HBIG and lamivudine compared with that of HBIG monotherapy to prevent recurrent HBV infection in patients undergoing orthotopic liver transplantation (OLT).

De novo tumors after liver transplantation: A single-center experience

ORGAN transplant recipients are considered to be at increased risk of malignancy because of prolonged immunosuppression therapy. Reported incidence rates range between 3% and 15%, twice that of the general population. De novo nonlymphoid solid tumors are an important cause of late allograft morbidity and patient mortality. The aim of the present study was to characterize the incidence and types of malignancies associated with liver transplantation in a single center. The analysis assessed the risk factors, clinical characteristics, and outcome of de novo malignancies particularly tumor-specific mortality.

Association of post-liver transplantation diabetes mellitus with hepatitis C virus infection

DDIABETES mellitus is a common complication of orthotopic liver transplantation, with an incidence of 5% to 27%. Although the disorder is generally attributed to the long-term use of immunosuppression agents, diabetes mellitus has been associated in recipients who undergo transplantation for hepatitis C virus (HCV) infection. The aim of the present study was to assess the prevalence and predictive factors for posttransplant diabetes mellitus (PTDM).

Effect of a Legal Initiative on Deceased- and Living-Donor Kidney Transplantation in Israel

The severe organ shortage in Israel has prompted many patients to undergo kidney transplantation abroad. In May 2008, the Israeli Knesset approved the Israel Transplant Law prohibiting organ trade and disallowing health insurers to reimburse the cost of illegal transplantation abroad. The aim of this study was to assess the initial effect of the law on kidney transplantations inside and outside the country. The number of kidney transplantations performed inside and outside Israel was compared between the 3-year periods before and after implementation of the transplant law (2006-2008 and 2009-2011). Further analysis compared the number of deceased-donor and live-donor transplantations performed in Israel during the same periods. The results showed that the number of transplants performed abroad dropped significantly, from a median of 143 per year during 2006-2008 to <45 per year during 2009-2011. There was a parallel increase in the number of kidney transplantations from living donors, from a median of 56 transplants per year in 2006-2008 to 78 per year in 2008-2011, with a peak of 117 transplants in 2011. In conclusion, the Israel Transplant Law has dramatically affected kidney transplantation practices in Israel by reducing transplantation tourism and increasing living-donor kidney transplantations.

Cholestasis and hypoalbuminemia as predictors of outcome after liver transplantation

WITH THE SEVERE organ shortage worldwide there has been a trend in recent years toward an increased use of liver allografts from older and otherwise suboptimal donors. The main disadvantage of this donor pool is the increased risk for primary graft non-function (PNF) on initial poor graft function (IPF) after transplantation. Whereas the criteria for retransplantation are well established for patients with PNF recipients with IPF, because of the possibility of full recovery often experience a delay in retransplantatation, which may explain the relatively high mortality rates among recipients with IPF. Several parameters have been proposed as potential prognostic markers for graft survival. Because transplant outcome depends on multiple donor, operative, and recipient factors, most predictive models lack accuracy. For patients with PNF, coagulation function and biochemical parameters are helpful to indicate the need for retransplantation. Severe preservation injury is characterized by cholestasis with rising bilirubin, alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGT) levels that peak at the 10th day posttransplantation. We hypothesized that persistence of abnormalities of these cholestatic parameters beyond day 10 after transplantation may predict subsequent graft loss in patients with IPF.