N Ascher

University of California, San Francisco, San Francisco, California, United States

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Publications (62)250.5 Total impact

  • Transplantation 01/2004; 78. · 3.78 Impact Factor
  • Transplantation 01/2004; 78:491-492. · 3.78 Impact Factor
  • Transplantation Proceedings 01/2001; 33(7-8):3646-8. · 0.95 Impact Factor
  • Gastroenterology 01/2001; 120(5). · 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. · 9.86 Impact Factor
  • Transplantation 01/1999; 67(7). · 3.78 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
  • Gastroenterology 01/1998; 114. · 12.82 Impact Factor
  • Transplantation 01/1998; 1. · 3.78 Impact Factor
  • Dixon B. Kaufman, Nancy L. Ascher
    Transplantation 01/1998; 66(9):269-272. · 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 12/1997; 3(6):559-62.
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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. · 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. · 3.78 Impact Factor
  • Journal of Pediatric Gastroenterology and Nutrition - J PEDIAT GASTROENTEROL NUTR. 01/1996; 23(3).
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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. · 3.78 Impact Factor
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    ABSTRACT: The aims of this pilot study were to evaluate the safety and efficacy of interferon-alpha 2b for treatment of hepatitis C virus infection in liver transplant recipients, to monitor changes in hepatitis C virus RNA levels with treatment and to determine pretreatment parameters predictive of a complete response. Eighteen patients with documented hepatitis C virus viremia and histological evidence of hepatitis after liver transplantation received 3 million units of alpha interferon three times weekly for at least 4 mo. Pretreatment serum aminotransferase levels were at least 1.5 times the upper limit of normal and no patient had concomitant hepatitis B virus infection. Response to therapy was defined as normalization of both aspartate and alanine aminotransferase at the end of treatment. Five patients (28%) had a complete response, whereas 13 (72%) had persistent elevation of one or both aminotransferases (nonresponders). At the end of therapy, hepatitis C virus RNA levels were reduced in both responders and nonresponders (p = 0.043 and 0.039, respectively by Wilcoxon signed rank test). After cessation of treatment, aminotransferases remained normal in four of five responders but serum hepatitis C virus RNA levels returned to pretreatment levels in responders and nonresponders. There was no significant change in histological score with therapy. Responders were more likely than nonresponders to have low pretreatment hepatitis C virus RNA levels and low serum bilirubin (p = 0.0004 and 0.0077, respectively). Responders tended to have a prolonged interval between transplantation and initiation of therapy (p = 0.10 by rank logistic regression analysis). Side effects resulted in early cessation of therapy in two patients and dose reduction in six.(ABSTRACT TRUNCATED AT 250 WORDS)
    Hepatology 11/1994; 20(4 Pt 1):773-9. · 12.00 Impact Factor
  • Transplantation Proceedings 05/1993; 25(2):1766-7. · 0.95 Impact Factor
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    ABSTRACT: To examine whether unknown viruses or autoimmune processes contribute to the development of cryptogenic liver disease, we studied 48 patients undergoing liver transplantation who had non-A, non-B cirrhosis; non-blood-borne cirrhosis of unknown etiology; or autoimmune cirrhosis. After the diagnosis of hepatitis C virus infection was established by the presence of viral antibodies or viral RNA, patients were reclassified into three groups: hepatitis C virus infection, autoimmune cirrhosis and cryptogenic cirrhosis. Explant histological appearance, incidence of posttransplant hepatitis and immunological features were compared in the three groups. Thirty-one percent of patients had neither hepatitis C virus infection nor classical autoimmune cirrhosis and were classified as having cryptogenic cirrhosis. Unlike histological appearance in hepatitis C virus infection but similar to that in autoimmune cirrhosis, explant histological appearance of cryptogenic cirrhosis showed inactive cirrhosis with little inflammation. After transplantation, histological hepatitis of the allograft was demonstrated in 44% of patients with hepatitis C infection but in no patient with autoimmune or cryptogenic cirrhosis. The autoimmune score, developed from clinical criteria associated with autoimmune liver disease, was significantly lower in cryptogenic cirrhosis and hepatitis C virus infection than in autoimmune cirrhosis. Autoantibodies--including antinuclear antibodies, smooth muscle antibodies and liver-kidney microsomal antibodies--were not commonly present in serum of patients with cryptogenic cirrhosis, whereas antibodies to soluble liver antigens were found with increased frequency in this entity. We conclude that in many patients with liver disease, no pathogenesis can be identified.(ABSTRACT TRUNCATED AT 250 WORDS)
    Hepatology 05/1993; 17(4):593-8. · 12.00 Impact Factor
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    ABSTRACT: Hepatitis B recurrence remains a major problem facing liver transplantation programs. The risk of infection varies depending upon the HBV load. High doses of HBIg may reduce the risk of occurrence but it remains expensive. Finally, apparently new infections may occur posttransplantation, which may have been transmitted by organs or blood from HBsAg (-), HBcAb (+) donors, or may reflect reactivation of latent infections in patients who were HBsAg (-). HCV infections are common in patients undergoing liver transplantation, and HCV infection recurs in > 90% of patients; however, recurrent hepatitis C occurs in less than half of these patients. HCV is not an important cause of fulminant non-A, non-B hepatitis, but appears to be the most common cause of posttransplant hepatitis. So what is in the future? For hepatitis B, we still believe the efficacy of HBIg, and in which patients with hepatitis B HBIg should be used, remains to be defined. The effects of antivirals on posttransplant hepatitis B, as well as in prevention of HBV recurrence, also remain to be determined. In the United States, insurance companies are likely to play an important role in determining the future of transplantation for hepatitis B. Medicare recently excluded patients who were HBsAg (+) from coverage for liver transplantation, and a number of private insurers have subsequently followed suit. For HCV, newer screening tests for the virus are likely to decrease the rate of HCV acquisition following liver transplantation, from the current 35% incidence of HCV acquisition. The impact of antiviral treatment on posttransplant hepatitis remains to be determined and deserves study. Finally, the development of regimens that might allow prevention of recurrent HCV infections in patients undergoing liver transplantation also should be a matter of future study.
    Transplantation Proceedings 04/1993; 25(2):2006-9. · 0.95 Impact Factor
  • Source
    L Ferrell, N Bass, J Roberts, N Ascher
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    ABSTRACT: A distinct peliosis-like lesion arose in the liver allograft of a 51 year old man. This lesion was caused by necrotic, fat-laden hepatocytes that released fat globules into the sinusoids. These then became strikingly distended with cysts, thus mimicking peliosis hepatitis. It is suggested that this lesion be called lipopeliosis.
    Journal of Clinical Pathology 01/1993; 45(12):1109-10. · 2.44 Impact Factor

Publication Stats

1k Citations
250.50 Total Impact Points

Institutions

  • 1992–2001
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, California, United States
  • 2000
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
  • 1997
    • University of Virginia
      • Department of Surgery
      Charlottesville, VA, United States
  • 1984
    • University of Minnesota Medical Center, Fairview
      Minneapolis, Minnesota, United States
  • 1980
    • University of Minnesota Duluth
      Duluth, Minnesota, United States