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Biomedical subjects

Eytan Mor

Publications and source records attributed to Eytan Mor.

At least 19 recordsLinked to original sources

Pregnancy in renal transplant recipients: long-term effect on patient and graft survival. A single-center experience.

BACKGROUND: There are limited data on the effect of pregnancy on long-term renal allograft function. The aim of the study was to compare long-term graft and patient outcome between pregnant and nonpregnant women after renal transplantation. METHODS: The study group consisted of 39 women attending the Perinatal Division of the Rabin Medical Center who conceived after undergoing renal transplantation (total number of live births: 55). All had a functioning allograft at the time of conception. Each patient was matched with 3 controls for 12 factors known to affect graft survival. The controls were derived from a cohort of 250,000 transplant patients registered in the Collaborative Transplantation Study (CTS) database. The groups were compared for graft survival, long-term patient survival, and kidney function (CTS clinical grading scale). RESULTS: Graft (61.6%) and patient (84.8 %) survival from transplantation to the end of follow-up (15 years) in the women who conceived after transplantation did not differ from the rates observed in the 177 women in the matched control group (68.7% and 78.8 %, respectively). There were no between-group differences in long-term graft function. CONCLUSION: Pregnancy does not appear to have adverse effects on long-term graft or patient survival or kidney function in women after renal transplantation.

Adolescent↗

Platelet-derived growth factor gene polymorphism in recurrent hepatitis C infection after liver transplantation.

BACKGROUND: Recurrent hepatitis C virus (HCV) infection is particularly aggressive in the post liver transplantation setting, with rapid progression of liver fibrosis. Platelet-derived growth factor (PDGF) is reportedly involved in the pathogenesis of liver fibrosis. The aim of this study was to evaluate the possible contribution of molecular variants of the PDGF-B gene to recurrent HCV infection after liver transplantation. METHODS: DNA was extracted from peripheral blood mononuclear cells of 40 patients who underwent liver transplantation for chronic HCV infection and genotyped for polymorphisms in PDGF-B at positions +1135 (A to C) and +286 (A to G). Intrahepatic PDGF-B expression was detected by immunohistochemistry and assessed semiquantitatively. Forty-seven healthy individuals served as controls. RESULTS: Recurrent HCV infection occurred in 34 patients (85%) after a median interval of 10.5 months (range 1.5-60.0). A statistically significant difference was observed in the distribution of the PDGF-B gene polymorphism at position +1135, but not +286 between patients and controls (P=0.05). The A/A genotype occurred at a highly significantly increased rate in patients with recurrent HCV infection than in those without (64.7% vs. 16.67%, P=0.0001), and in patients with severe than in those with nonsevere recurrence (100% vs. 53.85%, P=0.05). The expression level of intrahepatic PDGF-B was found to be highly correlated with the fibrosis stage (P<0.0001). Further analysis yielded a highly statistically significant relationship between the PDGF-B gene polymorphism at position +1135 and clinical parameters of disease severity. CONCLUSIONS: PDGF-B gene polymorphism appears to be associated with severe recurrent HCV infection after liver transplantation. PDGF-B may play an essential role in the development and progression of hepatic fibrosis. These findings, if confirmed, may have important therapeutic implications.

Female↗

[Changes in the transplantation world--from altruism to a utilitarian approach].

The lack of organs for transplantation is a worldwide problem that has created a moral conflict between the traditional altruistic basis of organ donation and alternative solutions based on utilitarian grounds. Survival of grafts achieved in recent decades after unrelated living-donor kidney transplantation between spouses is longer than with deceased donor transplantation. This experience justified the extension of kidney donation beyond the traditional close family relationships including: anonymous donors and paired exchange programs. However, unrelated donation of kidneys within altruistic norms could not provide an ultimate solution for the lack of organs for transplantation. On the other hand, globalization and development of advanced medical technology in developing countries that do not provide transplantation for all their citizens, created an opportunity for a worldwide flourish of transplant tourism as an alternative solution for transplant candidates. Transplant tourism functions according to market laws and is profit-driven, as opposed to the legal organ exchange programs in Europe and the U.S.A., which are non-profit and patient-oriented. The transition from trade in kidneys from unrelated living-donors to the use of other organs (heart, lung and liver) from death penalty prisoners in China was only a matter of deciding where to lay the moral border when justifying the act for the sake of life-saving. Considering the inability of current legal altruistic transplantation practice to supply the growing need for organs, healthcare authorities and professional transplantation organizations have to tackle the donor crisis by designing legally acceptable utilitarian solutions. For instance, through the formation of international organ exchange programs under formal agreements or, in the case of kidney transplantation, through the establishment of a regulated compensated donation system.

Altruism↗

Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells.

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue.

Adenoviridae↗

Percutaneous transluminal angioplasty of an occluded surgical splenorenal shunt in a 4-year-old child after liver transplantation.

Percutaneous transluminal angioplasty is increasingly used in children. We present a case of successful balloon angioplasty of an occluded surgical splenorenal shunt in a 4-year-old child who underwent liver transplantation because of biliary atresia. Percutaneous reopening of the shunt is a relatively safe procedure that may spare patients of surgical intervention.

Angioplasty, Balloon↗

Organ trafficking: scope and ethical dilemma.

The Israeli experience discloses the relationship between the traditional altruistic basis of organ donation and the new alternatives based on a utilitarian conception of unrelated compensated donation. Although organ trafficking in Israel was dramatically intensified, cadaveric and living-related donations decreased. Reforms in living donations, such as evaluation committees for unrelated directed donors, were insignificant in terms of meeting the demand of patients and reducing the volume of trafficking. It is our contention that battling organ trafficking should provide patients with a realistic alternative for kidney donations. Our model of regulated nondirect paid donations is planned to legalize significant compensation for the unrelated donors drawing individuals from falling into the trap of organ traders. This program, together with uncompromised penalties, would hopefully eradicate organ trafficking.

Altruism↗

Donor-specific hyporesponsiveness in ELISPOT assay is associated with early recurrence of hepatitis C in liver transplant recipients.

Recurrence of hepatitis C in liver transplant recipients is a common event that often leads to loss of the allograft. There are no means to prevent, or even predict, those patients who are more prone to early aggressive recurrence. Therefore there is an increased need for tailored immunosuppression protocols specific to this patient population. Fifteen liver transplant recipients (eight hepatitis C virus [HCV]+; 7 HCV-) were followed for 12-24 months after transplantation. The frequency of donor-specific interferon (IFN)-gamma- or interleukin-10-producing lymphocytes was monitored using ELISPOT assays. Of the eight HCV+ recipients, six experienced recurrence within the first year after transplant. All six patients had very low (negligible) frequency of donor-specific IFN-gamma precursors; in most cases not higher than the nonstimulated (spontaneous) secretion rate. The other two patients who did not recur exhibited donor-specific IFN-gamma reactivity. A significant difference in the frequency of alloantigen-specific T cells was observed between HCV+ recipients and patients with other indications for transplantation. The results of this preliminary study suggest that posttransplant monitoring of the frequency of donor-specific IFN-gamma-producing precursors may differentiate a subset of patients at risk for early recurrent hepatitis C and therefore may help to devise treatment strategies for HCV+ liver recipient after transplantation.

Aged↗

Negative impact of 'old-to-old' donations on success of cadaveric renal transplants.

The effect of 'old-to-old' cadaveric renal transplants on operative complications and graft survival was assessed in all 325 patients undergoing solitary cadaveric renal transplantations in Israel during a 3-yr period. Preoperative information and hospital course data were abstracted from the charts. Results were analyzed using Kaplan-Meyer survival curves, univariate and multivariate Cox models. Overall, 62 (19.1%) grafts failed within a year. Failure rate was 46.2% for 'old-to-old' transplants compared with 15.5% for all other donor/recipient age combinations (p < 0.0001). 'Old-to-old' transplants remained independently associated with graft failure in a multivariate Cox model after controlling the effect of other risk factors. 'Old-to-old' transplants were also associated with increased operative complications relative to other age combinations. The decision to use 'old-to-old' transplants, even when donors are scarce, is problematic and should be reconsidered.

Age Factors↗

Role of cytokine gene polymorphism and hepatic transforming growth factor beta1 expression in recurrent hepatitis C after liver transplantation.

Recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) is nearly universal. Cytokines play an important role in the immune response to viral infection, and cytokine gene polymorphism affects the overall expression and secretion of cytokines. The objective of this study was to define the relationship between cytokine polymorphism and recurrent hepatitis C after OLT. Blood samples were collected from 36 patients at a mean of 44.6+/-30.4 months after OLT for chronic HCV infection. DNA was extracted from peripheral blood mononuclear cells, and polymerase chain reaction-sequence specific primers (PCR-SSP) analysis was performed on promoter sequences of transforming growth factor beta1 (TGF-beta1), interleukin 6 (IL-6) interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (INF-gamma). Liver biopsies performed at diagnosis of recurrent disease were graded with the Knodell score, and hepatic TGF-beta1 expression was determined semiquantitatively by immunohistochemistry. The gene polymorphism of TGF-beta1 was correlated with its expression on hepatocytes and sinusoids. Polymorphism in all studied cytokine genes was correlated with recurrence, and interval to recurrence (>12 or < or =12 months post-OLT), and clinical (ascites, Child-Pugh score and death), biochemical parameters of recurrent HCV (serum alanine aminotransferase (ALT)), INR, albumin, bilirubin), and virological parameters (HCV genotype and load). Biopsies revealed recurrent HCV in 31 patients (86.1%); in 21 (67.7%), the interval to recurrence was 12 months. There was a statistically significant correlation between TGF-beta1 gene polymorphism, i.e., the genetic ability to produce high levels of TGF-beta1, and the intensity of TGF-beta1 staining on hepatocytes (p=0.003) and sinusoids (p=0.003), and the degree of fibrosis (p=0.02). A borderline correlation was found with the presence of ascites (p=0.007), but not with Child-Pugh score, synthetic liver function tests or HCV genotype and load. The genetic ability to produce low levels of IFN-gamma was correlated with recurrent disease (p=0.015). No such correlation was found for TGF-beta1 gene polymorphism. In conclusion, polymorphism in the TGF-beta1 gene correlates with its in situ hepatic expression in patients with recurrent HCV after liver transplantation. INF-gamma, but not TGF-beta1 gene polymorphism, correlates with early recurrent hepatitis C after transplantation. These findings might help to design preemptive prevention therapy in selected patients at risk.

Cohort Studies↗

Transhepatic balloon dilatation of early biliary strictures in pediatric liver transplantation: successful initial and mid-term outcome.

PURPOSE: To evaluate the initial and mid-term outcomes of transhepatic balloon dilatation for the treatment of early biliary strictures in lateral left-segment liver transplants in young children. METHODS: Between April 1997 and May 2001, seven children aged 9 months to 6 years with nine benign strictures in left-segment liver grafts were treated percutaneously. Sessions of two or three dilations were performed three or four times at average intervals of 10-20 days. In each session, the biliary stenoses were gradually dilated using balloons of 3-7 mm. Follow-up ranged from 12 to 54 months (mean 27 months, median 12 months). Clinical success was defined as resolution of the stenosis, normalization of liver enzymes and lack of clinical symptoms RESULTS: Technical success was achieved in all nine strictures. Hemobilia occurred in one patient and was successfully treated. On follow-up, all patients had complete clinical recovery with normalization of liver function and imaging of patent bile ducts. CONCLUSION: Balloon dilatation is an effective and relatively safe method for the treatment of early biliary strictures in left-segment liver transplantation in young children. We recommend this approach as the initial treatment for early strictures. Metal stents or surgery should be reserved for patients with late appearance of strictures or failure of balloon dilatation.

Anastomosis, Surgical↗

Serum cholestasis markers as predictors of early outcome after liver transplantation.

BACKGROUND: Early cholestasis is not uncommon after liver transplantation and usually signifies graft dysfunction. The aim of this study was to determine if serum synthetic and cholestatic parameters measured at various time points after transplantation can predict early patient outcome, and graft function. METHODS: The charts of 92 patients who underwent 95 liver transplantations at Rabin Medical Center between 1991 and 2000 were reviewed. Findings on liver function tests and levels of serum bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) on days 2, 10, 30, and 90 after transplantation were measured in order to predict early (6 months) patient outcome (mortality and sepsis) and initial poor functioning graft. Pearson correlation, chi(2) test, and Student's t-test were performed for univariate analysis, and logistic regression for multivariate analysis. RESULTS: Univariate analysis. Serum bilirubin >/=10 mg/dL and international normalized ratio (INR) >1.6 on days 10, 30, and 90, and high serum ALP and low albumin levels on days 30 and 90 were risk factors for 6-month mortality; serum bilirubin >/=10 mg/dL on days 10, 30, and 90, high serum ALP, high GGT, and low serum albumin, on days 30 and 90, and INR >/=1.6 on day 10 were risk factors for sepsis; high serum alanine aminotransferase, INR >1.6, and bilirubin >/=10 mg/dL on days 2 and 10 were risk factors for poor graft function. The 6-month mortality rate was significantly higher in patients with serum bilirubin >/=10 mg/dL on day 10 than in patients with values of <10 mg/dL (29.4% vs. 4.0%, p = 0.004). Patients who had sepsis had high mean serum ALP levels on day 30 than patients who did not (364.5 +/- 229.9 U/L vs. 70.8 +/- 125.6 U/L, p = 0.005). Multivariate analysis. Significant predictors of 6-month mortality were serum bilirubin >/=10 mg/dL [odds ratio (OR) 9.05, 95% confidence intervals (CI) 1.6-49.6] and INR >1.6 (OR 9.11, CI 1.5-54.8) on day 10; significant predictors were high serum ALP level on day 30 (OR 1.005, 1.001-1.01) and high GGT level on day 90 (OR 1.005, CI 1.001-1.01). None of the variables were able to predict initial poor graft functioning. CONCLUSIONS: Several serum cholestasis markers may serve as predictors of early outcome of liver transplantation. The strongest correlation was found between serum bilirubin >/=10 mg/dL on day 10 and early death, sepsis, and poor graft function. Early intervention in patients found to be at high risk may ameliorate the high morbidity and mortality associated with early cholestasis.

Alkaline Phosphatase↗

Scintigraphic patterns of veno-occlusive disease in liver transplantation.

Venous vascular complications in liver transplant recipients are rare. Diagnosis is usually based on clinical criteria and typical findings on liver biopsy. The scintigraphic patterns of posttransplant liver veno-occlusive disease are described, and the value of follow-up studies is suggested. The authors present 2 patients who developed posttransplantation hepatic veno-occlusive disease. The first patient had a severe form of the disease and a fatal outcome. The second patient had a mild to moderate form of this disorder with complete resolution following treatment.

Aged↗

Genotype prevalence, viral load and outcome of hepatitis B virus precore mutant infection in stable patients and in patients after liver transplantation.

OBJECTIVE: The precore mutant is detectable in most Israeli patients with persistent hepatitis B virus (HBV) infection. The aim of this study was to determine the prevalence of HBV genotypes, viral load and outcome of precore mutant infection in stable patients and in patients after liver transplantation. METHODS: The prevalence of HBV genotype and viral load were investigated in 81 patients with HBV precore mutant infection. Of these, 50 patients (40 males, 10 females; mean age 43.4 +/- 11.0 yr) underwent liver transplantation and were serum HBV DNA-negative by hybridization at the time of transplantation. Patients received long-term HBV immunoprophylaxis and immunosuppression, and lamivudine in cases of graft HBV recurrence. The remaining 31 patients were stable, with serum anti-HBe-positivity. Genotypes were tested by restriction fragment length polymorphism of an S gene amplicon. Precore mutations were studied with an INNO-LiPA probe assay. RESULTS: Follow-up was 46.6 +/- 37.7 months. Most of the transplanted group was of Middle Eastern origin (53.6%); the remainder were from Eastern Europe (21.4%), Western Europe and the USA (10.8%), Africa (7.1%), and Asia (7.1%). In the transplanted group, the pre-transplant HBV genotype D was the most prevalent (96%), while genotype A was found in only 4%. Eleven patients (22%) developed recurrent HBV infection post-transplantation. There were no differences in genotype distribution between patients with graft reinfection or lamivudine resistance and patients without recurrence. Mean viral load at recurrence was 148.4 x 10(6) +/- 60.4 x 10(6) copies/mL. The stable group had a similar origin and HBV genotype prevalence, but a lower mean viral load of 12.4 x 10(6) +/- 29.4 x 10(6) copies/mL (p = 0.007). The prevalence of mutations at the precore region and codon 28 was similar in both groups. CONCLUSIONS: The chronic precore mutant HBV-infected patients were characterized as follows: (i) genotype D was the most frequent genotype, (ii) the HBV genotype distribution was similar in patients with stable infection and after liver transplantation, (iii) viral load at recurrence was significantly higher than in stable infection, and (iv) HBV genotype was unrelated to the development of recurrence or lamivudine resistance in the tested population.

Adult↗

Factors associated with primary and secondary graft failure following cadaveric kidney transplant.

The risk profile for primary renal graft failure is largely unknown because of its inclusion with secondary failures or its exclusion from analysis. This study compares characteristics of the cadaveric transplant recipients who experienced primary failure, secondary failures or survived with a functioning graft for at least 6 months. Medical records of all cadaveric kidney-transplant patients performed in Israel over a 3-yr period 1997-2000 were reviewed. Fisher's exact test and multinomial regression models were used to assess the association of demographic, pre-operative and operative risk factors with the two types of failure outcomes. Of 325 grafts, 54 (16.6%) failed of which half were primary failures. Univariate analysis demonstrated a significant trend of increasing proportion of patients with specific risk factors from the functioning grafts group to the secondary and to the primary graft failure groups. Independent risk factors for primary graft failure included 'surgical complications', 'donor's age > or =60 yr', 'waiting for transplant > or =6 yr', and 'human leukocyte antigen-DR (HLA-DR) mismatch', based on the multivariate model. These factors may reflect the scarcity of organ donations in Israel, which leads to a prolonged waiting time, higher tolerance for HLA-DR mismatches, and utilization of kidneys from elderly donors.

Age Factors↗

[Pediatric liver transplantation--experience at Schneider Children's Medical Center].

BACKGROUND: Introduction of segmental graft transplantation from living donors and split livers from cadaver donors has led to major advances in liver transplantation (LTx) in children. AIM: To report our initial experience with pediatric LTx performed at our center. METHODS: Data collection on all children undergoing LTx between the years 1996-2003 including the analysis of the graft and patient survivals and reports of complications. RESULTS: Forty LTx were performed in 38 children at the mean age of 6.2 years, including two retransplants. There were 15 whole liver allografts and 25 segmental grafts including: 12 living donor grafts, 5 splits and 8 reduced grafts from cadaver donors. At 40 months mean follow-up period, patient and graft survival were 81% and 72.5%, respectively. There was post-transplant mortality in seven cases--5 children died during the first month and two children passed away after 6 months (recurrent disease) and 14 months (metastatic tumor). Vascular complications included: one early and one late portal vein thrombosis (5%) and six cases of hepatic artery thrombosis (15%). In the latest group, 3 grafts were salvaged by thrombectomy and another 3 children underwent re-transplantation. There were two bile leaks (5%) and 6 bile duct strictures (15%). The bile-duct strictures were successfully corrected by surgery in one child and by transhepatic dilatation in another 4 children. One child remained with intrahepatic strictures in one of the two hepatic segments. CONCLUSIONS: The use of segmental liver allografts enables the performance of pediatric liver transplantation in Israel. Gathered experience and enhanced skills will ensure improved results over time.

Adolescent↗