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Biomedical subjects

Paul J Marotta

Publications and source records attributed to Paul J Marotta.

8 recordsLinked to original sources
PubMed2006

Poor prediction of the glomerular filtration rate using current formulas in de novo liver transplant patients.

The utility of formulas estimating glomerular filtration rate (GFR) in liver transplant patients has not been well described. The purpose is to determine the correlation between the radionuclide GFR (rGFR) with formulas commonly used to estimate GFR. This study represented a secondary outcome measure of a multicenter randomized trial comparing the effectiveness of two immunosuppressive regimens in adult liver transplant patients (n=148). A total of 68 rGFR were measured, 33 at baseline and at 35 at three months after transplantation. GFR was estimated using 1/Scr and Cockcroft-Gault, MDRD, and Nankivell equations. At both time points assessed, all correlations with rGFR were poor: 1/Scr (r: 0.17 and 0.25), Cockcroft-Gault (r: 0.31 and 0.35), MDRD (r: 0.27 and 0.35), and Nankivell (r: 0.11 and 0.20). Accepted formulas to estimate GFR correlate poorly with rGFR during the first three months after liver transplantation. Recalibration of these formulas is required to improve the estimation of GFR in liver transplant patients.

Canada↗
PubMed2005

Evaluation of renal function in liver transplant recipients receiving daclizumab (Zenapax), mycophenolate mofetil, and a delayed, low-dose tacrolimus regimen vs. a standard-dose tacrolimus and mycophenolate mofetil regimen: a multicenter randomized clinical trial.

Posttransplant chronic renal failure, secondary to calcineurin inhibitor agents, is emerging as a major problem in liver transplantation. We report a randomized clinical trial comparing daclizumab, delayed low-dose tacrolimus (target trough level 4-8 ng/mL, starting day 4-6), Investigational Arm (n = 72), to standard tacrolimus induction/maintenance dosing, Standard Arm (n = 76), with mycophenolate mofetil and tapering corticosteroids in both study arms. The end-points were renal function indicated by the Modification of Diet in Renal Disease (MDRD). There was no significant difference in patient survival (86.6% Investigational Arm vs. 92.9% Standard Arm; P = 0.21) or acute rejection (23.2% vs. 27.7%, respectively; P = 0.68). Statistically significant differences in median glomerular filtration rate (GFR) were found in favor of the Investigational Arm. With the CG equation, the GFR at the end of the first week was 110.7 vs. 89.6 mL/min (P = 0.019) without significant differences thereafter. With the MDRD, statistically significant differences extended to the first posttransplant month (86.8 vs. 70.1 mL/min/1.73 m(2); P < 0.001) with and was seen at month 6 (75.4 vs. 69.5 mL/min/1.73 m(2); P = 0.038). In conclusion, delayed low-dose tacrolimus, in combination with daclizumab and mycophenolate mofetil, preserves early renal function post-liver transplantation without the cost of increased acute rejection.

Antibodies, Monoclonal↗
PubMed2005

Liver transplantation for incidental cholangiocarcinoma: analysis of the Canadian experience.

Cholangiocarcinoma is a biliary tumor, which not infrequently complicates primary sclerosing cholangitis. It carries a poor prognosis and, with the exception of carefully selected individuals in research protocols, contraindicates orthotopic liver transplantation. There has been some suggestion that cholangiocarcinomas incidentally discovered at the time of transplantation carry a better prognosis. The goal of this retrospective study was to perform a national review of outcomes after liver transplantation in Canadian recipients found to have incidental cholangiocarcinoma in their explanted native liver. Six of the seven liver transplant centers in Canada provided clinical and follow-up information on all liver transplant recipients found to have incidental cholangiocarcinoma in their explants. The diagnosis or suspicion of cholangiocarcinoma prior to transplantation were exclusion criteria for this study. Ten individuals with cholangiocarcinoma were transplanted between 1996 and 2003. The median duration of follow-up was 28 months. Eight of the 10 had PSC. All of the tumors were stage I or II. The 3-year survival for these patients was 30%. The median time to recurrence was 26 months (95% confidence interval 13-37), and the median time to death was 30 months (95% confidence interval 28-53). In conclusion, although early survival of patients transplanted for incidental cholangiocarcinoma appears good, intermediate- and long-term survival rates are not better than for individuals historically transplanted with known cholangiocarcinoma. Aggressive investigation for cholangiocarcinoma is mandated. Incidentally found tumours remain a difficult treatment problem, and prospective adjuvant chemo-, radio-, and immunotherapies should be investigated.

Adult↗
PubMed2005

Transplant immunosuppressive agents in non-transplant chronic autoimmune hepatitis: the Canadian association for the study of liver (CASL) experience with mycophenolate mofetil and tacrolimus.

BACKGROUND: Conventional treatment of autoimmune hepatitis consists of either prednisone alone or in combination with azathioprine. Ten to 20% of patients do not respond to or are intolerant of this treatment. Novel drug treatments include immunosuppressive drugs such as tacrolimus (TAC), mycophenolate mofetil (MMF), methotrexate and cyclosporine. We describe a multi-centre Canadian experience with MMF and TAC. OBJECTIVE: To study a multi-centre patient population who had failed conventional therapy and were treated with non-conventional medical therapy for autoimmune hepatitis and document response. METHODS: Members of the Canadian Association for the Study of Liver (CASL) obtained MMF from Hoffmann-La Roche Ltd, as part of a compassionate release program, were contacted for standardized data on patients with AIH who received MMF or TAC. Response definitions based on aminotransferase changes were: Complete response (CR)-sustained normalization, partial response (PR)-improvement by greater than 50%, non-response (NR)-less than 50% improvement and relapse (RP)-initial CR or PR followed by an increase in aminotransferases. RESULTS: A total of 16 patients were identified: six in Ontario, one in Quebec, five in Alberta and four in British Columbia. Three were treated with TAC, eleven with MMF and two with combination MMF and TAC. CR was observed in 50%, PR in 12.5%, RP in 25% and NR occurred in 12.5%. The CR for MMF without TAC was approximately 64%. CONCLUSIONS: MMF is effective and well tolerated by patients with autoimmune hepatitis who do not respond to, or are intolerant of, conventional immunosuppressive agents.

Adult↗
PubMed2004

The challenge of recurrent hepatitis C virus in liver transplant recipients.

Hepatitis C virus (HCV) has become the leading indication for liver transplantation (LT) worldwide. Short-term graft and patient survival after LT in these individuals is comparable with other indications for LT. There is, however, a disturbing trend for decreased survival over the longer term. The natural history of HCV infection after LT is evolving. Its early recurrence and the wide spectrum of recurrent disease is recognized, from minimal histological and clinical disease to very aggressive forms of hepatic damage such as fibrosing cholestatic hepatitis. There is growing concern that recurrent HCV is becoming more aggressive. Although many factors have been implicated, the causes have not been fully elucidated. Interferon-based antiviral therapy is challenging to use in this patient population because of significant toxicity. Nevertheless, these agents have some efficacy, and pegylated interferons, which are now being used more frequently, achieve superior response rates. The role of liver retransplantation in this patient population is controversial, because of both a reduced survival rate and an overall shortage of organ donors. The present review discusses the challenges that occur in LT recipients with HCV.

Antiviral Agents↗