N Ascher

Hospital Universitari i Politècnic la Fe, Valenza, Valencia, Spain

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Publications (78)387.08 Total impact

  • Transplantation 01/2004; 78:491-492. DOI:10.1097/00007890-200407271-01324 · 3.78 Impact Factor
  • Transplantation 01/2004; 78. DOI:10.1097/00007890-200407271-00389 · 3.78 Impact Factor
  • Transplantation Proceedings 11/2001; 33(7-8):3646-8. DOI:10.1016/S0041-1345(01)02569-6 · 0.95 Impact Factor
  • Gastroenterology 04/2001; 120(5). DOI:10.1016/S0016-5085(01)80268-7 · 12.82 Impact Factor
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    ABSTRACT: The natural history and predictors of HCV-related disease severity post-transplantation are uncertain. The aims of this study were to define the natural history of post-transplantation HCV infection by assessing the rate of fibrosis progression, to determine if the post-transplantation natural history differs from that observed pre-transplantation, and to identify predictors of post-transplantation disease progression. Post-transplantation biopsies (mean: 3+/-1.6/patient) from 284 patients were scored according to histologic stage, using the method of Desmet et al. Change in fibrosis score (fibrosis progression/year) post-transplantation was used as the primary outcome. Predictors analyzed included viral factors (genotype and viral load at transplantation), patient demographics, year of transplantation, country of transplantation, pre-transplantation fibrosis progression, immunosuppression and laboratory data. There was a linear association between change in fibrosis score and time from transplantation, with a median rate of fibrosis progression per year of 0.3 (0.004-2.19/year). Using parametric time-to-event analysis, the expected median duration to cirrhosis was 10 years. The rate of post-transplantation fibrosis progression was significantly higher than pre-transplantation (0.2/year (0.09-0.8) p<0.0001), and higher in Spanish than US centers (0.48 (0.01-2.19) vs 0.28 (0.004-2.08); p=0.09) despite similar progression rates prior to transplantation. Variables independently associated with post-transplantation progression included year of transplantation (p=0.0001), race (p=0.02), number of methyl-prednisolone boluses (p=0.03), and HCV RNA levels at transplantation (p=0.01). HCV-related disease progression is accelerated in immunocompromised compared to immunocompetent patients, with a progressive increase in patients who have recently undergone liver transplantation. Changes in patient management post-transplantation over time and between transplant centers may account for the increase in fibrosis progression observed in recent years.
    Journal of Hepatology 05/2000; 32(4):673-84. DOI:10.1016/S0168-8278(00)80231-7 · 10.40 Impact Factor
  • Transplantation 01/1999; 67(7). DOI:10.1097/00007890-199904150-00574 · 3.78 Impact Factor
  • Gastroenterology 04/1998; 114(4). DOI:10.1016/S0016-5085(98)85365-1 · 12.82 Impact Factor
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    ABSTRACT: This is a discussion of transplant surgery fellowship training issues that pertain to educational quality guidelines of fellowship programs, the number of fellows being trained, and the individual's fate in securing transplant surgery positions after training. In 1995, the Council of the American Society of Transplant Surgeons (ASTS) revised the academic guidelines to enhance the educational standards of programs seeking ASTS approval as a transplant surgery fellowship training program. The criteria for accrediting training programs in kidney and liver transplant surgery were redefined, and new criteria for pancreas transplant surgery training were developed. Regarding the number of transplant surgery fellows being trained per year, during the period from 1991 to 1997, a total of 327 transplant surgery fellows completed training at ASTS-accredited transplant surgery fellowship training programs. The annual number of transplant surgery fellowship graduates has remained nearly constant at approximately 45 per year. However, the proportion of transplant surgery trainees who are foreign medical graduates has increased annually since 1995. Currently, 49% of the trainees are foreign medical graduates. Regarding the individual's fates in securing transplant surgery positions after training, the proportion of U.S./Canadian medical graduates who received transplant surgery training during the last year but are practicing in surgical disciplines other than transplant surgery appears to be increasing. Before 1996, it was rare for transplant surgery trainees to pursue surgical practice activities that did not include transplantation. Among the current group of 28 U.S./Canadian medical graduates who completed transplant surgery training between January 1997 and July 1997, six did not secure an acceptable position in transplantation. Instead, they are practicing in either general surgery or vascular surgery, or obtaining additional transplant training. These changes in the demographics and dynamics of transplant surgery fellowship training activity provoke important concerns.
    Transplantation 01/1998; 65(2):269-272. · 3.78 Impact Factor
  • Dixon B. Kaufman, Nancy L. Ascher
    Transplantation 01/1998; 66(9):269-272. DOI:10.1097/00007890-199801270-00023 · 3.78 Impact Factor
  • Transplantation 01/1998; 1. DOI:10.1097/00007890-199805131-00187 · 3.78 Impact Factor
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    ABSTRACT: Many centers perform biopsies on transplanted livers annually to assess allograft function because serum biochemical tests do not always correlate with histological findings. Although criteria exist for diagnosing acute cellular rejection, no similar criteria exist to describe the histopathological changes observed in the "normal" liver of an immunosuppressed but healthy child. The purpose of this study was to define the histopathological changes in the allografted livers of healthy children who have undergone transplantation and to evaluate them during long-term follow-up. One hundred fifty-eight yearly protocol liver biopsy specimens of 54 children who received transplants between January 1988 and March 1996 and at least 1 year of follow-up were reviewed, and the biopsy findings were correlated with those of serum tests of liver function performed concomitantly. Thirty-three biopsy specimens were excluded because serum transaminase levels were abnormal, the biopsy specimen was abnormal and diagnostic for a specific lesion, or follow-up showed progression of a specific disease process. In addition, time zero biopsy specimens from 21 of the 54 children were available for comparison. In the protocol biopsy specimens, portal and/or parenchymal mononuclear inflammatory infiltrates were frequent findings (48% and 25%, respectively). Other less common features were mild fibrosis (8%) and focal pericholangitis (6%). Findings in both protocol and time zero biopsy specimens included minimal to mild bile ductular proliferation (15% and 9.5%, respectively) and rare hepatocyte necrosis (1.6% and 5%). No yearly protocol biopsy specimens resulted in any patient benefit. Transplanted livers in immunosuppressed children who are clinically healthy and have normal transaminase levels commonly show histological changes consisting of scattered, mild to moderate, portal and/or parenchymal mononuclear infiltrates that are clinically insignificant. Yearly protocol biopsies in healthy pediatric recipients have been abandoned by the investigators after 3 years of follow-up.
    Liver transplantation and surgery: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 11/1997; 3(6):559-62. DOI:10.1002/lt.500030601
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    ABSTRACT: The outcome of orthotopic liver transplantation (OLTX) in patients retransplanted for severe hepatitis B virus (HBV) in the first allograft has been poor due to high rates of HBV reinfection and even more aggressive disease in the second graft. Recent data suggest that hepatitis B immunoglobulin (HBIg) given after transplantation can be successful in delaying or preventing HBV reinfection in patients transplanted for chronic hepatitis B cirrhosis. We report the successful retransplantation of patients who developed recurrent or de novo hepatitis B after OLTXY. Using similar HBIg regimens, two centers retransplanted seven patients after they developed recurrent or de novo hepatitis B in the first allograft. At retransplantation all seven patients were HBs antigen (Ag) positive; four patients were positive for HBeAg and HBV DNA by immunoblot assay, two patients were negative for HBeAg and HBV DNA, and one patient was positive for HBV DNA and negative for HBeAg. All patients were either HDV Ag or anti-HDV negative. One patient was anti-HCV positive. All patients received HBIg infusions after retransplantation to maintain serum anti-HBs levels >500 IU/L indefinitely. After retransplantation, six of seven patients are alive (86%): all are without evidence of HBV recurrence with serum negative for HBsAg, HBeAg, and HBV DNA by immunoblot assay. Liver biopsies are normal on routine studies with immunohistochemical stains for HBcAg and HBsAg also being negative. Mean follow-up of these six patients is 40.1 months (range 21-63 months). One patient (14%) developed HBV reinfection 7 months after his second transplant, in spite of maintaining target anti-HBs levels. He maintained stable liver function with minimal evidence of clinical hepatitis B, but died 8 months later from an unrelated stroke. We conclude that patients with recurrent or de novo hepatitis B after OLTX can be successfully retransplanted using aggressive immunoprophylaxis to prevent HBV reinfection. The failure of HBIg therapy in one patient underscores the need for other effective adjunctive anti-HBV modalities.
    Transplantation 09/1997; 64(3):410-4. DOI:10.1097/00007890-199708150-00006 · 3.78 Impact Factor
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    ABSTRACT: Background. The transjugular intrahepatic portosystemic shunt (TIPS) is an important treatment for complications of portal hypertension. As some authors have suggested that TIPS may facilitate liver transplantation technically, the objective of this study was to determine the impact of TIPS on the liver transplant operation and its outcome. Methods. The analysis was designed as a retrospective cohort study using a multicenter database. Fifty-five patients with TIPS were matched with 55 controls on the basis of 10 pretransplant laboratory, clinical, and demographic features. TIPS patients and control patients were compared with regard to duration of surgery, intraoperative blood product usage, liver and renal function, volume of ascites, survival, and hospital stay. For confirmatory purposes, a parallel analysis using linear regression methods was performed. Results. By matched analysis, TIPS patients had less ascites at surgery (mean 0.9±0.20 vs. 2.2±0.37 L, P=0.005) and a slightly shorter time from incision to cross-clamp (mean 2.1±0.10 vs. 2.5±0.15 hr, P=0.03). However, there were not significant differences for total operative time (mean 6.0±0.17 vs. 6.3±0.25 hr, P=1.00), blood product usage, or any other outcome variable. Regression analysis confirmed these results. Conclusions. TIPS does not significantly impact the course of liver transplantation surgery. Therefore, preoperative portal decompression solely to facilitate liver transplantation is not an appropriate indication for TIPS.
    Transplantation 04/1997; 63(8):1074-1079. DOI:10.1097/00007890-199704270-00005 · 3.78 Impact Factor
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    Nancy L. Ascher
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    ABSTRACT: Recombinant adenovirus vectors are efficient at transferring genes into somatic tissues but are limited for use in clinical gene therapy by immunologic factors that result in the rapid loss of gene expression and inhibit secondary gene transfer. This study demonstrates that systemic coadministration of recombinant adenovirus with soluble CTLA4lg, which is known to block co-stimulatory signals between T cells and antigen presenting cells, leads to persistent adenovirus gene expression in mice without long-term immunosuppression. This form of immunotherapy greatly enhances the likelihood that recombinant adenovirus vectors will be useful for human gene therapy.Recombinant adenoviruses are attractive vehicles for liver-directed gene therapy because of the high efficiency with which they transfer genes to hepatocytes in vivo. First-generation recombinant adenoviruses deleted of E1 sequences also express recombinant and early and late viral genes, which lead to development of destructive cellular immune responses. Previous studies indicated that class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTLs) play a major role in eliminating virusinfected cells. The present studies utilize mouse models to evaluate the role of T-helper cells in the primary response to adenovirus-mediated gene transfer to the liver. In vivo ablation of CD4+ cells or interferon γ (INF-γ) was sufficient to prevent the elimination of adenovirus-transduced hepatocytes, despite the induction of a measurable CTL response. Mobilization of an effective TH1 response as measured by in vitro proliferation assays was associated with substantial upregulation of MHC class I expression, an effect that was prevented in IFN-γ-deficient animals. These results suggest that elimination of virus-infected hepatocytes in a primary exposure to recombinant adenovirus requires both induction of antigen-specific CTLs as well as sensitization of the target cell by the TH1-mediated activation of MHC class I expression.
    Liver Transplantation 09/1996; 2(5). DOI:10.1002/lt.500020513 · 3.79 Impact Factor
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    Nancy L. Ascher
    Liver transplantation and surgery: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 03/1996; 2(2):168-9. DOI:10.1002/lt.500020215
  • Journal of Pediatric Gastroenterology and Nutrition 01/1996; 23(3). DOI:10.1097/00005176-199610000-00064 · 2.87 Impact Factor
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    ABSTRACT: Liver granulomas have long been known to pose diagnostic problems for pathologists; however, their prevalence and associated etiologic factors have not been studied in liver transplant patients. We reviewed 3632 liver biopsy specimens from 563 patients at two institutions and identified 42 patients with posttransplant granulomas. A possible or probable etiologic factor was identified in 30 (71%) cases. Most were epithelioid granulomas and microgranulomas located in the parenchyma associated with hepatocyte necrosis (21 cases, 50%). Portal-based granulomas were associated with recurrent primary biliary cirrhosis (5 cases, 12%), acute cellular rejection (2 cases, 4.8%), and a foreign body-type reaction (1 case, 2.4%). One case was associated with tuberculosis (2.4%), 4 cases occurred in a fatty liver (9.5%), and 8 patients had liver granulomas but no other significant abnormality. The granulomas were most frequent in the first 7 months after transplantation when the patients were biopsied more often and underwent episodes of rejection or acute hepatitis. Portal-based granulomas in this period were usually associated with acute cellular rejection. After 7 months, the frequency of granulomas as well as the number of biopsies decreased and portal-based granulomas associated with recurrent primary biliary cirrhosis were most common (5 cases, 12%). Rare, late-appearing parenchymal granulomas were also seen (3 cases) and consisted of 1 lipogranuloma and 2 cases of epithelioid granuloma. The latter were thought, in 1 patient, to be associated with parenchymal hepatocyte necrosis; the others were of unknown etiology.
    Transplantation 12/1995; 60(9):926-33. DOI:10.1097/00007890-199511150-00008 · 3.78 Impact Factor
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    Nancy L. Ascher
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    ABSTRACT: The shortage of liver grafts results in the fact that 8% of potential recipients die before receiving a graft. Liver graft division has therefore been proposed to maximize the current available liver graft pool. However, the question of benefit or additional risk for the recipients that this technique might carry remains unanswered. The European Split Liver Registry was opened in March 1993 and reviewed retrospectively the clinical experience obtained at nine European centers regarding the use of split liver transplants, during the five year period from March 1988 to March 1993. From 50 donors livers, 100 grafts were prepared: 2 grafts were discarded and the other 98 were transplanted in 53 children (2 times in 3 children) and 42 adults (2/42 heterotopic position). Sixty-three grafts were implanted in an urgent recipient (half of whom had acute hepatic failure). Portal vein thrombosis, hepatic artery thrombosis, biliary complications and retransplantation rates were 4%, 11.5%, 18.7% and 18.7% respectively. Most of these complications were unrelated to the technique itself. Actual 6 month graft survivals of elective and urgent orthotopic transplants were 80% and 61.3% in children, and 72.2% and 55.6% in adults; actual 6 month patient survivals rates for similar groupings were 88.9% and 61.1% and 80% and 67.7% respectively. Similar rates were reported after conventional transplant in Europe. It is concluded that split liver transplantation is an efficient transplant technique that benefits both urgent patients who otherwise could have died before getting a graft in time and elective patients.The minimum graft volume still remains unclear in reduced-size liver transplantation (RLT). This study reports the improved survival of canine RLT using a quarter graft with the aid of a portahepatic vein shunt (PHVS). In beagles, the donor liver was reduced to the right lateral and caudate lobes (quarter graft) with or without provision of PHVS, and transplanted orthotopically in the recipient. The PHVS was established by an end-to-end anastomosis of the portal vein branch and the hepatic vein in the resected left lateral lobe. Liver chemistries including arterial blood ketone body ratio (AKBR) were serially measured during and after surgery. All seven animals with PHVS survived more than 3 days (mean ± SD; 5.3 ± 1.7 days) whereas all six without PHVS died within 3 days (1.8 ± 0.8 days, P < 0.01). Portal vein pressures immediately after recirculation in animals with and without PHVS were 8.5 ± 1.2 mmHg and 16.9 ± 3.1 mmHg respectively (P < 0.01). Regardless of the presence or absence of PHVS, AKBR dropped to a level lower than 0.7, during the anhepatic period and returned promptly to above 1.0 as early as 30 min after recirculation. Thereafter, the AKBR values in animals with PHVS remained higher than 1.0, whereas those in animals without PHVS showed a progressive decrease, showing a statistically significant difference between the two groups after 12 hr (P < 0.05). Graft function, as assessed by AKBR, was well correlated with survival and other liver chemistries. These results indicate that, in an extreme RLT, portal hypertension is a risk factor predisposing to graft failure, most likely by increasing microvascular injury after recirculation.Hyperacute rejction of vascularized porcine to primate xenografts is initiated by the binding of xenoreactive natural antibodies to donor endothelium. We tested the hypothesis that the level of xenoantigen exnoantigen expression varies in the population of potential poricine donors and may determine the amount of binding of xenoreactive natural antibodies to a porcine organ perfused by xenogeneic blood. Two hundred ninety pigs were studied using an inhibition ESISA that quantitated the xenoantigen level on porcine platelets. Based on this assay, the levels of xenoantigen expression in the population adhered to a normal distribution. Kidneys from pigs found to express high antigen levels and kidneys from pigs found to expres high antigen levels and kidneys from pigs found to express low antigen levels were perfused with baboon blood using an extracorporeal circuit. In multiple experiments, a significant difference was observed in the amount of xenoreactive natural antibody adsorbed by high antigen versus low antigen organs. Normalizing for the weight of the perfused organs fro levels of natural antibody in individual baboons, high antigen organs adsorbed 3.6 ± 1.3 U of xenoreactive natural antibody/g and low antigen organ adsorbed −0.8± 1.0U of xenoreactive natural antibody/g (p
    Liver Transplantation 11/1995; 1(6). DOI:10.1002/lt.500010612 · 3.79 Impact Factor
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    Nancy L. Ascher
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    ABSTRACT: The shortage of organs for transplantation is especially severe for the critically ill newborn infant, for whom donors of the appropriate size are particularly scarce. One way to overcome this problem is to use animals in lieu of human as organ donors. The major limitation to using animals for this purpose is the susceptibility of animal organs to hyperacute rejection, a violent rejection reaction thought to be mediated by antidonor antibody and complement. To evaluate the potential application of xenotransplantation to newborns, we tested neonatal humans and neonatal baboons, and found that neither populatioh expressed significant levels of xenoreactive antipig antibodies. We transplanted heterotopically hearts from newborn pigs into unmanipulated newborn baboons (n = 4). There was no evidence of hyperacute rejection in any of the grafts; the animals were killed with functioning grafts at 15, 81, and 82 hour. This outcome contrasts with that of newborn pig-to-mature baboon and mature pig-to-mature baboon cardiac xenografts, which were rejected within one hour of transplantation. The histology of pig graft biopsies from the new born recipients was normal. Immunohistochemistry revealed only traces of IgM, C3, C4 and the membrane attack complex along graft endothelium. Fibrin deposition along endothelial surfaces was observed early after transplantation and became more extensive with time; in the absence of endothelial bound antibody or complement, this change may represent preservation injury. This study suggests that due to low levels of natural antibody, the newborn infant may permit prolonged xenograft survival.
    Liver Transplantation 09/1995; 1(5):320-321. DOI:10.1002/lt.500010508 · 3.79 Impact Factor
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    ABSTRACT: The waiting list for liver transplantation has more than doubled between 1988 and 1992, yet the number of liver transplantations during the same period increased by only 79%. This discrepancy is due to the limited availability of donors. The modest increase in donor pool is caused entirely by donors > or = 40 years of age, a trend likely to continue. To determine the impact of increasing donor age on the outcome of liver transplantation, we analyzed 6-month graft survival in 7,988 adults who received first liver graft between October 1987 and September 1992, and were observed through the United Network for Organ Sharing Scientific Liver Transplant Registry. Graft survival was measured by death and/or retransplantation, donor age by decades. The independent effect of donor age on graft survival was estimated by Cox regression analysis controlling for the possible confounding of donor, recipient, and institutional characteristics. Between 1987 and 1992, the percentage of donors over 50 years increased from 2.1% to 17.5% resulting in change of median donor age from 23 to 31 years. For donor age > or = 50, graft failure rate was 50% higher than with donor age less than 20 years (excess for mortality was 25% and for retransplantation 94%). Adjustment for characteristics associated to donor age or outcome did not eliminate the excess risk found with increasing donor age. Despite these adversities, graft failure rate in recipients from oldest donors (27.2%) in 1992 was nearly equivalent to recipients from the youngest donors (26.9%) in 1987 to 1988. Although increasing donor age has an adverse effect on 6-month graft survival, improvement in transplantation technology and patient care over time have more than compensated for poorer graft function associated with the simultaneous rise in median donor age.
    Liver transplantation and surgery: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 09/1995; 1(5):311-9. DOI:10.1002/lt.500010507

Publication Stats

3k Citations
387.08 Total Impact Points

Institutions

  • 2000
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
  • 1997
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 1992–1996
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, California, United States
  • 1995
    • National Institutes of Health
      • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      Bethesda, MD, United States
  • 1980–1988
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 1984
    • University of Minnesota Medical Center, Fairview
      Minneapolis, Minnesota, United States