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Eytan Mor

Publications and source records attributed to Eytan Mor.

29 records · Page 2Linked to original sources

Kidney transplantation from living-unrelated donors: comparison of outcome with living-related and cadaveric transplants under current immunosuppressive protocols.

OBJECTIVES: Living-unrelated donors may become an additional organ source for patients on the kidney waiting list. We studied the impact of a combination of calcineurin inhibitors and mycophenolate-mofetil together with steroids on the outcomes of living-related (LRD), unrelated (LUR), and cadaver transplantation. METHODS: Between September 1997 and January 2000, 129 patients underwent LRD (n = 80) or LUR (n = 49) kidney transplantation, and another 173 patients received a cadaveric kidney. Immunosuppressive protocols consisted of mycophenolate-mofetil with cyclosporine-Neoral (41%) or tacrolimus (59%) plus steroids. We compared the patient and graft survival data, rejection rate, and graft functional parameters. RESULTS: LRD recipients were younger (33.6 years) than LUR (47.8 years) and cadaver (43.7 years) donor recipients (P <0.001). HLA matching was higher in LRD patients (P <0.001). Acute rejection developed in 28.6% of LUR versus 27.5% of LRD transplants and 29.7% of cadaver kidney recipients (P = not significant). The creatinine level at 1, 2, and 3 years after transplant was 1.63, 1.73, and 1.70 mg% for LRD patients; 1.48, 1.48, and 1.32 mg% for LUR patients; and 1.75, 1.68, and 1.67 mg% for cadaver kidney recipients (P = not significant), respectively. No difference in patient survival rates was found among the groups. The 1, 2, and 3-year graft survival rates were significantly better in recipients of LRD (91.3%, 90.0%, and 87.5%, respectively) and LUR transplants (89.8%, 87.8%, and 87.8%, respectively) than in cadaver kidney recipients (81.5%, 78.6%, 76.3%, respectively; P <0.01). CONCLUSIONS: Despite HLA disparity, the rejection and survival rates of LUR transplants under current immunosuppressive protocols are comparable to those of LRD and better than those of cadaveric transplants.

Adult↗

Neoral dose monitoring using 2-hour cyclosporine post-dose levels in stable children with liver transplants: improvement in renal function.

In adult liver transplant recipiens, 2-h post-Neoral (C2) dose monitoring is associated with a lower incidence and severity of acute cellular rejection and improved renal function than C0 (trough level) monitoring. This study examined whether switching from C0 to C2 monitoring during maintenance also improves renal function in pediatric liver transplant recipients. Three boys aged 11-16 yr with stable graft function at 6-50 months after liver transplantation were switched from C0 to C2 monitoring. Median C0 was 148 ng/mL (range 100-186), and median C2 was 767 ng/mL (range 702-1187). At the time of conversion, C2 levels exceeded the recommended targets (0-6 months 1000 ng/mL; > 12 months 600 ng/mL in all children). Within 3 months, serum creatinine level decreased by a median of 42.8%, and glomerular filtration rate increased by a median of 86%. No clinical or biochemical evidence of rejection was noted during the 6-month follow-up. Our results suggest that in pediatric liver transplant recipients, C2 monitoring is associated with greater improvement in renal function than C0 monitoring; switching to C2 monitoring can correct cyclosporine-associated toxicity.

Adolescent↗

Intrahepatic cholestasis after liver transplantation.

Cholestasis is a common sequela of liver transplantation. Although the majority of cases remain subclinical, severe cholestasis may be associated with irreversible liver damage, requiring retransplantation. Therefore, it is essential that clinicians be able to identify and treat the syndromes associated with cholestasis. In this review, we consider causes of intrahepatic cholestasis. These may be categorized by time of occurrence, namely, within 6 months of liver transplantation (early) and thereafter (late), although there may be an overlap in their causes. The causes of intrahepatic cholestasis include ischemia/reperfusion injury, bacterial infection, acute cellular rejection, cytomegalovirus infection, small-for-size graft, drugs for hepatotoxicity, intrahepatic biliary strictures, chronic rejection, hepatic artery thrombosis, ABO blood group incompatibility, and recurrent disease. The mechanisms of cholestasis in each category and the clinical presentation, diagnosis, treatment, and outcome are discussed in detail.

Cholestasis, Intrahepatic↗

Genotypic and phenotypic resistance: longitudinal and sequential analysis of hepatitis B virus polymerase mutations in patients with lamivudine resistance after liver transplantation.

OBJECTIVE: Lamivudine-resistant strains appear in 27-62.5% of liver transplant recipients treated with lamivudine for hepatitis B virus (HBV) recurrence, and may lead to failure of antiviral therapy. In an extension of our previous study, we investigated the molecular events associated with the emergence of lamivudine-resistant mutants in this population. METHODS: Sequential serum samples from 10 consecutive patients with lamivudine resistance after liver transplantation were analyzed for viral genotype, precore mutants, and viral polymerase gene mutants (L528M, M552V, M552I) using restriction fragment length polymorphism. Quantitative analysis of HBV DNA was performed using hybridization assay and polymerase chain reaction. RESULTS: Eight patients (80%) were infected with genotype D and two (20%) with genotype C. Polymerase mutants (genotypic resistance) were identified in all the patients. Phenotypic resistance (rise in serum HBV DNA titers above the detection limit of the hybridization assay) developed in five patients (50%); of the remainder, three (30%) did not have phenotypic resistance, and two were primary nonresponders. Genotypic resistance was detected earlier than phenotypic resistance (median 285 days [range 42-510] vs median 387 days [range 320-420], p = 0.055). In five patients (50%), the emergence of the YMDD mutants took over the wild type; in three (30%), the YMDD mutant took over the wild type, but the wild type re-emerged during lamivudine therapy; and in two (20%), the YMDD mutants were detected in a mixture with the wild type (in different percentages). The mean pretreatment serum ALT level was significantly lower in the patients who did not develop phenotypic resistance (p = 0.0002). The M552I pure viral population was found mainly in these patients, and all retained stable graft function (median follow-up 33 months). A high pretreatment HBV DNA level (>50 x 10(6) copies/ml) was highly statistically significantly correlated with the rapid occurrence of phenotypic resistance (r = -0.90, p = 0.04). CONCLUSIONS: We reached the following conclusions: 1) In our area, liver transplant recipients who develop resistance to lamivudine given for recurrent HBV infection seem to be mainly infected with genotype D. 2) Re-emergence of the wild type can occur during lamivudine therapy. 3) Genotypic resistance precedes phenotypic resistance, although phenotypic resistance does not always follow genotypic resistance. 4) Quantitative determination of viremia and analysis of polymerase gene mutants are recommended for monitoring antiviral therapy of liver transplant patients with HBV reinfection in the graft.

Adult↗

Cytokine gene polymorphisms in patients infected with hepatitis B virus.

OBJECTIVE: Cytokines play a key role in the regulation of the immune response. The maximal capacity of cytokine production varies among individuals and correlates with the polymorphism in the cytokine gene promoters. The aim of this study was to characterize gene polymorphism in patients with chronic hepatitis B virus (HBV) infection and to determine the different patterns in patient subgroups. METHODS: The study population consisted of 77 patients with chronic HBV infection (23 low-level HBV replicative carriers, 23 compensated high-level HBV replicative carriers, 21 decompensated liver transplant candidates, and 10 patients with documented hepatocellular carcinoma). The genetic profile of five cytokines was analyzed by polymerase chain reaction-sequence-specific primer (SSP), and subjects were genotyped as high or low producers of tumor necrosis factor-alpha and interleukin (IL)-6, and as high, intermediate, or low producers of transforming growth factor-beta(1), interferon (IFN)-gamma, and IL-10 based on single nucleotide substitutions. The control group included 10 healthy individuals who recovered from HBV infection and 48 healthy controls. RESULTS: A highly statistically significant difference in the distribution of the IFN-gamma gene polymorphism (at position +879) was observed between patients with chronic HBV infection and controls. The majority of the patients (65.2%) exhibited the potential to produce low levels of IFN-gamma (A/A genotype) compared with 37.5% of the control group (p = 0.003). Healthy individuals who recovered from HBV infection had a similar distribution of IFN-gamma gene polymorphism as the healthy controls. No statistically significant difference in IFN-gamma production was found between patients with low- and high-level HBV replication and between compensated and decompensated patients. There was also no statistically significant difference in the genetic ability to produce tumor necrosis factor-alpha (at position -308), IL-6 (at position -174), IL-10 (at position -1082, -819, and -592), and transforming growth factor-beta(1) (at position +10 and +25). CONCLUSION: These findings suggest an association between the genetic ability to produce low levels of IFN-gamma and the susceptibility to develop chronic HBV infection.

Adult↗

Radiofrequency ablation for the management of liver tumors.

BACKGROUND: Radiofrequency ablation has recently become a viable treatment option for unresectable primary or secondary lesions confined to the liver. OBJECTIVE: To study the local therapeutic efficacy, side effects and complications of radiofrequency ablation for the treatment of hepatocellular carcinoma and liver metastases. This is the first reported experience of radiofrequency ablation for treating malignant hepatic tumors in Israel. METHODS: Fifteen consecutive patients, aged 53-73 years, with 23 lesions (8 patients with HCC and 7 with secondary liver tumors) underwent radiofrequency ablation under general anesthesia. RITA nine-array 5 cm thermal ablation catheter and the model 1500 generator were used. The mean diameter of all tumors was 4.28 cm (range 1-10 cm). Three lesions were 1-3 cm in diameter (small), 17 lesions measured 3.1-5 cm (medium), and 3 measured 5.1-10 cm (large). RESULTS: Complete necrosis was found in 8 (66%) of 12 HCCs by computed tomography scan. Of the remainder, diffuse tumor recurrence was demonstrated in three lesions (25%) after lipiodol injection and there was one local tumor recurrence. In the metastases group complete necrosis was found in 5 of 11 lesions (45%). One major complication (peritonitis) was treated with antibiotics and four (26%) minor complications (right pleural effusion, small subcapsular hematoma) were monitored. CONCLUSIONS: Radiofrequency ablation appears to be an effective, safe and relatively simple procedure for the treatment of liver tumors.

Aged↗

Kidney transplantation from living donors: comparison of results between related and unrelated donor transplants under new immunosuppressive protocols.

BACKGROUND: Recent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list. OBJECTIVES: To study the impact of the combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants. METHODS: Between September 1997 and January 2000, 129 patients underwent living related (n = 80) or unrelated (n = 49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups. RESULTS: LUD recipients were older (47.8 vs. 33.6 years) with a higher number of re-transplants (24.5% vs. 11.2% in LRD recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 years graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients. CONCLUSIONS: Despite HLA disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

Adult↗

Seroconversion after the addition of famciclovir therapy in a child with hepatitis B virus infection after liver transplantation who developed lamivudine resistance.

There is very little information about hepatitis B virus (HBV) infection in children after liver transplantation. This is the first report of the addition of famciclovir in a child who developed lamivudine resistance.A 5-year-old boy who was serum HBsAg-negative and was not vaccinated against HBV underwent living-related liver transplantation for fulminant hepatitis A. The donor was his mother, who was serum HBcAb-positive. No immunoprophylaxis was administered. HBV infection developed after 18 months and was treated with 3 mg/kg daily of lamivudine. Serum alanine aminotransferase normalized and HBV DNA load decreased significantly. Sixteen months later, lamivudine resistance developed; a mutation (M552I) was confirmed by sequencing through the YMDD locus of the HBV polymerase gene. The addition of 750 mg daily of famciclovir led to seroconversion and the disappearance of serum HBV DNA. Lamivudine in combination with famciclovir might be a therapeutic option for HBV reinfection after liver transplantation, also in children. Suppression of viral replication to undetectable values is possible even in the lamivudine-resistant mutant.

2-Aminopurine↗

[Living-related segmental liver transplantation: broadening application in adult recipients].

Living-related liver transplantation using the left lateral segment has evolved as a surgical procedure in response to the need for size-matched grafts for small children. Experience gained with this procedure over the last decade and superb results led many centers to apply similar techniques for use of the right lobe for adults. Right lobe living-related liver transplantation is advantageous mainly for patients who otherwise would have long waiting periods for cadaveric organs, such as those with cholestatic liver disease or stable cirrhotic patients with small hepatocellular carcinoma. However, it is important to remember that living donors are healthy volunteers, and the risk associated with right hepatectomy is considerably higher than the risk of left lateral segmentectomy. The estimated risk for morbidity, mainly for bile duct leaks and intra-operative blood loss is about 5%, and the risk for mortality after right lobectomy is 0.2-0.5%. Extended experience in liver resections and segmental liver transplantation techniques in children is a prerequisite before initiating an adult living-related program. In addition, use of strict criteria for donor and recipient selection may lessen the risk associated with living donor liver transplants and thus further justify its use.

Adult↗

[Porto-systemic shunts in children: Schneider Children's Medical Center experience].

UNLABELLED: Portal hypertension in the absence of liver disease in children remains a therapeutic challenge. Despite successful control of variceal bleeding in most children, the risk of massive GI bleeding and mechanical disturbance of a huge spleen associated with hypersplenism exists throughout life. Surgical shunt between the portal and systemic venous systems is considered a definitive solution for that problem. AIMS: We present our experience with the porto-systemic shunt for extrahepatic portal hypertension. PATIENTS AND METHODS: Nine children (mean age 11.4 years) with portal hypertension were referred for a shunt procedure during a 5-year period (1996-2001). We reviewed patients charts for clinical parameters before and after surgery as well as surgical data (type of shunt, portal pressure gradient). A mesocaval shunt was constructed in 5 children, a splenorenal shunt in 3 other children and one child with splenic vein thrombosis underwent splenectomy alone for presumed diagnosis of left sided portal hypertension. RESULTS: During a mean follow-up period of 21.2 months (range 6-63 months), the surgical shunt remained patent in 7 of the 8 children. An immediate drop in portal pressure and increased platelets count over time was noted in those 7 children. In two children high portal pressure persisted after surgery, including a child who underwent mesocaval shunt following a previous failed splenorenal shunt and another child who underwent splenectomy alone. None of the children bled following the shunt procedure and decreased splenic size was observed in the 3 children with massive splenomegaly. CONCLUSIONS: We suggest that the porto-systemic shunt is indicated for children with non-hepatic portal hypertension suffering with uncontrolled bleeding and those with massive splenomegaly associated with hypersplenism.

Adolescent↗