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Biomedical subjects

S Beckebaum

Publications and source records attributed to S Beckebaum.

11 recordsLinked to original sources
PubMed2006

Target range maximum of cyclosporine blood concentration two hours post dose in stable liver transplant patients.

Recently, single blood level measurement 2 hours after cyclosporine administration (C2) is taken as a more sensitive indicator of drug exposure in de novo transplant recipients than trough levels (C0). However, few studies focused on the determination of the C2 target range maximum and its associated adverse events in stable liver recipients. This prospective study was designed to assess the relative risk of developing CsA related side effects in patients with high C2-levels. Adverse effects were determined clinically, and by using a specially designed questionnaire. Eventual adverse events as well as C2 levels were determined repeatedly up to 4 times in 3-months intervals (observation period 9 +/- 3 months) in 36 long-term liver recipients (1-13.5 years post-transplant), in addition to conventional C0 levels. Cyclosporine dose was adjusted according to a predefined C0 target level range and clinical status. Totally 103 questionnaires and the corresponding paired CsA blood level records were obtained. C0 levels and C2 levels ranged from 90 to 287 (143 +/- 31) ng/ml and from 212 to 1358 (672 +/- 203) ng/ml respectively. No patient experienced a rejection episode during the observation period, demonstrating the efficiency of the immunosuppressive therapy. However, 33/36 patients (91%) showed symptoms attributable to CsA therapy. C2 levels above 750 ng/ml, determined at least twice in an interval of 3 months, were identified as a relevant risk factor for the presence of multiple adverse effects, which were defined as the combination of hypertension, renal insufficiency and more than two neurological complaints (RR = 3.11, p<0.01). This risk population was not completely identified by determination of C0 level.

Adult↗
PubMed2005

[New techniques in liver transplantation].

Due to innovative surgical techniques, improved immunosuppressive regimens and better postoperative management, orthotopic liver transplantation achieved patient and allograft survival rates of 80 to 90% that have expanded both the indications for transplantation as well as the number of potential recipients awaiting liver transplantation. One of the major challenges facing organ transplantation is the current shortage of donors. Despite supportive legislation, media network systems and the attempt to raise public awareness, the actual donor numbers have remained relatively constant and do not meet the growing need for more organs. In 2002 the mortality among patients waiting for a liver organ reached 20%. Among the several measures that can be undertaken to expand the donor pool is the use of previously unused donors, such as marginal livers, domino-, split- or living related liver transplantation.

Adult↗
PubMed2005

[Surgical and interventional treatment of liver metastases].

The liver is the most common target organ for metastatic disease. The majority of patients undergoing surgical treatment for liver metastases have colorectal primaries. Endocrine liver metastases, or metastases from other tumors such as mammary carcinoma, sarcomas, renal tumors or gastrointestinal stromal tumors (GIST) are appreciably less common for surgical treatment. The gold standard of treatment is resection of the metastatic lesions. In the meantime, advances in surgical techniques and improved perioperative patient management make it possible to perform extensive resections with acceptable morbidity and mortality rates. In the event of metastases that are not primarily resectable, various downstaging procedures are available, with the aid of which secondary resectability can be achieved. Among the interventional treatment options that should be applied only in palliative intent, radiofrequency ablation is in widespread use.

Antineoplastic Agents↗
PubMed2004

Future directions in immunosuppression.

As liver transplantation is now being performed with an excellent 5-year survival rate of approximately 70% at selected centers, attention has been shifted to reduce long-term complications of calcineurin inhibitors including diabetes, hypertension, and hyperlipidemia, which have a major effect on morbidity and mortality within the transplant setting. Cyclosporine (CsA) monitoring has been performed traditionally by measurement of predose "trough" blood concentrations (C0). Recent development of 2 hour postdose CsA (C2) monitoring strategy has emerged as a much more sensitive approach for assessing the pharmacokinetics and providing greater precision in the optimization of Neoral dosing than C0 measurements. Furthermore, a reduction of risk factors for atherosclerotic vascular disease and in the incidence and severity of acute cellular rejection have been associated with the adoption of C2 monitoring. However, further data from multicenter trials are required to evaluate the long-term benefits of this new therapeutic monitoring strategy.

Graft Rejection↗
PubMed2004

Combination therapy with peginterferon alpha-2B and ribavirin in liver transplant recipients with recurrent HCV infection: preliminary results of an open prospective study.

Allograft reinfection with hepatitis C virus (HCV) in transplant recipients occurs commonly and represents a major concern in the transplant setting. Suppression of viral replication in HCV transplant patients should prevent or delay progression to cirrhosis and graft failure. In this ongoing study, we present preliminary data from a prospective trial of standard interferon (IFN) alpha-2b (2 million units daily) for 3 months and subsequent peginterferon (PEG IFN) alpha-2b (1.5 microg/kg/week) for 9 months. IFN therapy was combined with ribavirin (10 to 12 mg/kg). So far, HCV has become undetectable by qualitative PCR in 33% of patients while 25% had a reduction of HCV RNA to undetectable by the bDNA assay and 42% had no virological response after 6 months of therapy. A biochemical response was detected in 42% of patients. Improvement of inflammatory activity was observed in 42% of patients after 6 months. In three patients anemia necessitated administration of erythropoietin and three patients received granulocyte-colony stimulating factor (G-CSF) due to leucopenia [corrected] In conclusion, we observed that daily IFN alpha-2b and subsequent PEG IFN alpha-2b therapy in combination with ribavirin provides biochemical and virological benefits in transplant recipients with established recurrent HCV infection.

Adult↗
PubMed2004

Impact of combined mycophenolate mofetil and low-dose calcineurin inhibitor therapy on renal function, cardiovascular risk factors, and graft function in liver transplant patients: preliminary results of an open prospective study.

As liver transplantation (LT) is now being performed with excellent 1-year graft survival rates of 85% to 90%, attention has been shifted to reducing long-term complications of calcineurin inhibitors (CNI). We randomized LT patients (2:1) who displayed renal dysfunction under CNI treatment to either mycophenolate mofetil (MMF) (1000 mg twice a day) followed by stepwise reduction of CNI (n = 21; Tac trough levels <4 ng/mL, CsA trough levels <50 ng/mL); or continue their current CNI dose (n = 11; control group). Three months after study entry, we observed significantly decreased mean values in the CNI reduction group of serum creatinine (1.88 +/- 0.36 versus 1.58 +/- 0.33 mg/dL, P < .001) and BUN (39.2 +/- 11.8 versus 29.9 +/- 9.59 mg/dL, P < .001) with a significantly increased GFR (51.4 +/- 10.8 versus 61.6 +/- 14.1 mL/min, P < .001). Improved renal function in these long-term LT recipients (5.6 +/- 3.6 years posttransplant; range, 2 to 13 years) suggests at least a partial reversibility of CNI-induced renal damage. Furthermore, we found an improved lipid profile as well as a significantly decreased mean systolic (140 +/- 19 versus 130 +/- 14 mm Hg, P < .01) and diastolic (82 +/- 9 to 74 +/- 8 mm Hg, P < .001) blood pressure 3 months after introduction of MMF therapy. Additionally, transaminases significantly improved in the CNI reduction group within this time period (ALT 37.9 +/- 25.9 versus 25.2 +/- 13.2, P < .05). MMF and CNI-reduced immunosuppressive regimens may improve long-term patient survival, suggesting a broad application within the liver transplant setting.

Aged↗
PubMed2004

CNI-sparing regimens within the liver transplant setting: experiences of a single center.

One- and 5-year survival rates after liver transplantation have improved with the development of potent immunosuppressive drugs. Thus, attempts have shifted to reduce long-term complications of CNI and prednisone therapy. Minimization of CNI and concomitant introduction of MMF has resulted in a significant improvement of renal function, blood pressure and triglyceride values in our transplant patients. In recipients who develop recurrent or de novo malignancies, SRL therapy might be recommended. In addition, the flexibility to individualize immunosuppression should be favored in selected patients. However, large prospective randomized trials are required in order to determine if SRL/low dose CNI or SRL monotherapy are reasonable options for prolonging patient survival. Moreover, important questions such as the appropriate SRL target dose for prevention of tumor growth need to be answered. Numerous studies investigating distinct immunosuppressive combination therapies and withdrawal or minimization of CNI are available in the literature; however it is not yet clear which treatment regimens will prove to be the most efficacious and least toxic.

Adult↗
PubMed2004

[Advances and limitations of liver transplantation in Germany].

Orthotopic liver transplantation (OLT) is now an established therapy for end stage liver disease as well as acute liver failure. Improvements in surgical techniques, meticolous selection of transplant candidates and advances in immunosuppression have markedly increased patient and graft survial. The demand for organ grafts has continuously increased. Living donor organ transplantation omits the problem of organ shortage with prolonged waiting times for OLT and the likelihood of disease progression especially in tumor patients. Advanced liver disease related to chronic viral hepatitis is one of the primary indications for OLT worldwide. Combination therapy with hepatitis B immunoglobulin and lamivudine has been widely adopted as an effective prophylactic treatment regimen against recurrent HBV infection. Reinfection of the allograft is obligate in viremic post transplant patients with HCV infection. However the use of pegylated interferon in combination with ribavirin holds promise for delaying rapid progression of HCV infection in the allograft and the need for retransplantation. Recurrence of PBC, PSC and autoimmune hepatitis affects between 20 % and 30 % grafts at 10 years but appears to have little impact on long-term graft function and survival. In patients with hepatocellular carcinoma fulfilling strict selection criteria for OLT, 5 year survival rates of approximately 75% have been reported.

Antiviral Agents↗
PubMed2003

Treatment of hepatitis B reinfection after liver transplantation.

Patients with chronic replicative hepatitis B virus (HBV) infection who undergo orthotopic liver transplantation (OLT) in the absence of prophylactic antiviral therapy have a high risk of graft reinfection. Serial monitoring of serum HBV DNA and HBV sequence analysis, especially of the polymerase and the "a" epitope of the surface antigen, may be a requisite diagnostic tool in order to provide optimal therapeutic management for inhibition of viral replication before and after OLT. Combination therapy with hepatitis B immunoglobulin (HBIG) and lamivudine has been widely adopted as an effective prophylactic treatment regimen against recurrent HBV disease. The major issue of concern has been the development of lamivudine resistance due to the emergence of mutations in the YMDD motif of the HBV DNA polymerase gene. Among newer antivirals, adefovir dipivoxil and entecavir have been demonstrated to be effective against both wild-type and lamivudine resistant mutants. Due to the availability of antiviral drugs, outcome of patient and graft survival has dramatically improved and has become similar or even better as compared to patients with non-HBV-related liver diseases.

Drug Therapy, Combination↗