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Peter Neuhaus

Publications and source records attributed to Peter Neuhaus.

At least 37 records · Page 2Linked to original sources
PubMed2006

Major influence of liver function itself but not of immunosuppression determines glucose tolerance after living-donor liver transplantation.

Controversial data exists concerning the impact of immunosuppressive therapy on the development of post-transplantation diabetes mellitus (PTDM). Therefore, we investigated glucose metabolism in healthy donors and in recipients of living-donor liver transplants (LD-LTX, n=18) without pre-existing diabetes mellitus before, on day 10, month 6, and month 12 after intervention. The computer-assisted analysis of glucose, insulin, and C-peptide profiles obtained from frequently sampled intravenous glucose tolerance tests allows to achieve an integrated view of factors controlling glucose tolerance, i.e., insulin sensitivity (SI), first and second phase insulin secretion (phi1 and phi2). SI of donors declined by day 10 after operation (SI 2.65 +/- 0.41 vs. 4.90 +/- 0.50 10(-4) minute(-1) microU ml(-1), P < 0.01) but returned to values as before after 6 months. Phi1 did not change. Phi(2), however, significantly increased by day 10 (8.57 +/- 0.82 10(9) minute(-1) to 13.77 +/- 1.53 10(9) minute(-1), P < 0.01) but was in the same range as before after 6 months. In parallel to donors SI of recipients progressively increased after LD-LTX. Phi1 did not alter in recipients. Phi2 continuously decreased and was not different from donors by month 12. The extent of liver injury assessed by liver enzyme concentrations and liver function represented by cholinesterase activity, albumin, and INR were closely related with changes of SI in donors and recipients during the first year after intervention. In conclusion, the extent of liver damage plays a predominant role in regulating glucose tolerance. No impact of immunosuppressive therapy on SI, phi1 and phi2 was detected.

Adult↗
PubMed2006

Influence of donor/recipient HLA-matching on outcome and recurrence of hepatitis C after liver transplantation.

The aim of this study was to analyze the effect of human leukocyte antigen (HLA) matching on outcome, severity of recurrent hepatitis C and risk of rejection in hepatitis C positive patients after liver transplantation (LT). In a retrospective analysis, 165 liver transplants in patients positive for hepatitis C virus (HCV) with complete donor/recipient HLA typing were reviewed for recurrence of HCV and outcome. Follow-up ranged from 1 to 158 months (median, 74.5 months). Immunosuppression consisted of either cyclosporine-A- or tacrolimus-based quadruple induction therapy including or an interleukin 2-receptor antagonist. Protocol liver biopsies were performed after 1, 3, 5, 7, and 10 years and staged according to the Scheuer scoring system. The overall 1-, 5-, and 10-year graft survival figures were 81.8%, 69.11 and 62%, respectively. There was no correlation in the study population between number of HLA mismatches and graft survival. The number of rejection episodes increased significantly in patients with more HLA mismatches (P < 0.05). In contrast to this, the fibrosis progression was significantly faster in patients with 0-5 HLA mismatches compared to patients with a complete HLA mismatch. In conclusion, HLA matching did not influence graft survival in patients after LT for end-stage HCV infection, however, despite less rejection episodes, the fibrosis progression increased in patients with less HLA mismatches within the first year after LT.

Brain Death↗
PubMed2006

Safety, tolerability, and efficacy of everolimus in de novo liver transplant recipients: 12- and 36-month results.

Everolimus is a macrolide immunosuppressive agent with known consistent absorption. In this double-blind study, we examined the safety and tolerability of everolimus vs. placebo in de novo liver transplant recipients. One hundred and nineteen liver allograft recipients were randomized to 1 of 4 groups: everolimus 0.5 mg bid, everolimus 1.0 mg bid, everolimus 2 mg bid, or placebo. Patients received oral cyclosporine to achieve a target trough level of 150-400 ng/mL in combination with prednisone. Primary and secondary endpoints of safety, tolerability, and efficacy were determined at 12 months, and patients were followed through 36 months. There was a trend toward fewer treated acute rejections in the everolimus group than in the placebo group: everolimus 0.5 mg: 39.3%; everolimus 1.0 mg: 30.0%; everolimus 2 mg: 29.0%; placebo: 40.0% (P = not significant). Adverse events were higher in everolimus-treated patients especially at the 4-mg/day dose, but there was no difference in the incidence of thrombocytopenia or leukopenia between all groups and renal function as determined by serum creatinine, and creatinine clearance remained stable to 36 months in everolimus-treated patients. Mean cholesterol and triglycerides increased from baseline in all treatment groups, and maximum levels were seen at 6 months. In conclusion, this study demonstrates that everolimus in combination with oral cyclosporine had an acceptable safety and tolerability profile, paving the way for additional studies in this transplant indication.

Adult↗
PubMed2006

Validation of cardiovascular risk scores in a liver transplant population.

Increased prevalence of cardiovascular risk factors has been acknowledged in liver transplant recipients, and an increased incidence of cardiovascular events has been suspected. Individual risk determination, however, has not yet been established. Outpatient charts of 438 primary liver transplants have been reviewed, and suspected cardiovascular risk factors were correlated with cardiovascular events observed during a follow-up period of 10 yr. Receiver operation characteristics curve (ROC) analysis was performed to validate established cardiovascular risk scores. For calibration, the Hosmer-Lemeshow test was performed. A total of 303 of 438 patients were available for risk factor analysis at 6 months and demonstrated complete follow-up data (175 male, 128 female). A total of 40 of those 303 patients experienced fatal or nonfatal cardiovascular events (13.2%). In univariate analysis, age (P < 0.001), gender (P = 0.002), body mass index (P = 0.018), cholesterol (P = 0.044), creatinine (P = 0.006), diabetes mellitus (P = 0.017), glucose (0.006), and systolic blood pressure (P = 0.043), but not cyclosporine A (P = 0.743), tacrolimus (P = 0.870), or steroid medication (P = 0.991), were significantly associated with cardiovascular events. Multivariate analysis, however, identified only age, gender, and cholesterol as independent predictors. In ROC analysis, corresponding areas under the curve for Systematic Coronary Risk Evaluation Project (SCORE), Prospective Cardiovascular Münster Study (PROCAM), and Framingham risk scores (FRSs) were calculated with 0.800, 0.778, and 0.707, respectively. Calibration demonstrated an improved goodness of fit for PROCAM compared to SCORE risk calculations. In conclusion, SCORE and PROCAM proved to be valuable in discriminating our liver transplant recipients for their individual risk of cardiovascular events. Furthermore, calibrated PROCAM risk estimates are required to calculate the number of patients needed to treat in the setup of prospective intervention trials.

Adult↗
PubMed2006

Immunogenicity and safety of an experimental adjuvanted hepatitis B candidate vaccine in liver transplant patients.

Patients with chronic liver disease are at higher risk of hepatitis B (HB) virus infection before and after liver transplantation, and they commonly have a suboptimal immune response to HB vaccines. In this randomized trial, we compared the immunogenicity of primary vaccination with 2 doses of an experimental adjuvanted HB vaccine (adjuvant system 04 containing aluminium and monophosphoryl lipid A [HB-AS04]) to that of 3 double doses of a licensed HB vaccine in 93 liver transplant candidates. Depending on the waiting list for liver transplantation, a booster dose of HB-AS04 or double booster dose of the licensed HB vaccine was given before or after surgery, at 6 to 12 months after initiation of the vaccination course. The percentage of subjects with seroprotective anti-HB surface antibody concentrations 1 month after booster was twice as high in the HB-AS04 group (60.0%), vs. patients in the comparator group (32.0%) (P = 0.035). In subjects who did not undergo liver transplantation before administration of the booster, better immunogenicity results were obtained: 80% of subjects were seroprotected after HB-AS04 vaccination vs. 60% with the comparator (P = 0.2302). Despite a slightly higher reactogenicity, the safety profile of the HB-AS04 vaccine was clinically acceptable. In conclusion, an improved antibody response was observed in liver transplant candidates with 3 doses of HB-AS04, as compared to 4 double doses of a comparator. Liver transplant candidates could benefit from the use of this experimental adjuvanted HB vaccine to further increase their protection against HB infection.

Adjuvants, Immunologic↗
PubMed2006

Low viscosity histidine-tryptophan-ketoglutarate graft flush improves subsequent extended cold storage in University of Wisconsin solution in an extracorporeal rat liver perfusion and rat liver transplantation model.

Adequate flushing for liver donation requires large fluid volumes delivered at a high flow. This can be achieved more effectively with crystalloid solutions than with colloid-based solutions. This study examined the combination of initial histidine-tryptophan-ketoglutarate solution (HTK) graft flush and subsequent storage in University of Wisconsin solution (UW) to that of the single use of each solution. Livers from inbred Wistar rats were procured using aortic perfusion with UW or HTK for initial perfusion and reflushed after 30 minutes using either solution. In a third group, after perfusion with HTK, organs were reflushed with UW. A 60-minute in-vitro recirculating perfusion was performed after 24 hours of cold storage in the subsequent solution, as well as allotransplantation after 18 and 24 hours of cold storage. In extracorporeal perfusion, the HTK flush followed by UW storage was superior compared to the single use of either UW or HTK solution, as measured by portal venous pressure, bile flow, liver enzymes released into the effluent perfusate, glycerol leakage, and histological examinations. These data were consistent with the transplantation study. Histological damage and enzyme release after 5-day survival were lowest in the HTK flush and subsequent UW storage groups following 18 hours of cold storage; likewise, the 5-day survival was superior following 24 hours of cold storage. In conclusion, the combined use of HTK solution for initial graft rinse and subsequent storage in UW solution resulted in a cumulative protection. Choosing low-viscosity HTK solution for the initial organ flush may represent a feasible improvement in liver preservation, which also further reduces the required amount of UW solution.

Adenosine↗
PubMed2006

The surgical approach for radiofrequency ablation of liver tumors.

Radiofrequency ablation for the treatment of liver tumors is one of the best alternative treatment modalities when surgical resection is not possible. To find the right indication for the treatment, every patient should be treated in a high-volume center for the treatment of liver tumors in an interdisciplinary conference consisting of liver surgeons, interventional radiologists, medical oncologists, and gastroenterologists. With a multimodal approach including anatomic segmental and wedge resection of the liver, RFA, and chemotherapy, a median survival of 36 months was achieved in technically unresectable patients with colorectal liver metastases (Elias et al. 2005). This survival doubles the survival rate of any other treatment modality in this group of patients. These interdisciplinary conferences also serve to determine the approach for RFA, whether it should be percutaneous, laparoscopic, or open surgery. The safest ablation with the fewest adverse events from RFA is the open surgical approach, followed by the laparoscopic approach. The approach with the highest risk of injury to organs in proximity to the liver is the percutaneous approach. Therefore, many variables must be evaluated before making definite decisions. After choosing RFA as the best alternative treatment option after evaluation of all variables for a particular patient, it offers a treatment option with a potential cure. A major advantage is the possible combination with liver resection, which extends the indication for surgical or ablative therapy.

Catheter Ablation↗
PubMed2006

Mycophenolate mofetil in liver transplantation--is monotherapy safe?

Liver transplantation (LTX) today has become a routine procedure granting curative treatment for various hepatic diseases with excellent survival rates. Constant improvement of immuno-suppressive regimens has led to significant reduction of rejection frequency and increased safety in long-term management. Calcineurin-inhibitors play the key role in most immunosuppressive protocols providing strong T-cell suppression yet often associated with numerous side-effects. Increasing renal insufficiency as well as hypertension, hyperglycaemia, hyperuricaemia, and increased risk of secondary malignancy account for the major problems in short- and long-term follow-up of LTX patients. Mycophenolate mofetil (MMF) as a purine-synthesis inhibitor has proved to be a potent immunosuppressive agent largely free of the CI-associated side-effects. MMF therefore has been used to modulate immunosuppressive protocols in order to both increase efficacy and to reduce CI-related side-effects such as nephrotoxicity. In recent years, MMF-monotherapy protocols have been suggested for LTX patients with renal insufficiency. This review provides an overview on the current role of MMF in immunosuppressive protocols after LTX and evaluates innovative therapeutic concepts.

Graft Rejection↗
PubMed2006

24-h storage of pig livers in UW, HTK, hydroxyethyl starch, and saline solution: is microdialysis an appropriate method for the continuous graft monitoring during preservation?

Recent studies demonstrate the feasibility of microdialysis to monitor metabolism in ischemic livers. Whether these parameters correlate with markers of liver cell integrity in an experimental model using pig livers and different preservation solutions was an aim of this study. Pig livers were flushed with either 4 degrees C Histidine-Typtophan-Ketoglutarate solution (HTK) (Custodiol), University of Wisconsin solution (ViaSpan), and hydroxyethyl starch, or 12 degrees C saline solution. After 24-h storage, the livers were rinsed with saline to measure liver enzymes and lactate from the effluate. Utilizing microdialysis, intraparenchymal lactate, pyruvate, glucose, and glycerol was monitored. Tissue biopsies were taken for histological examinations. Cold preservation resulted in a decrease of metabolic activity measured by intrahepatic glucose, lactate, and pyruvate levels, as well as lactate in the effluate, independently of the solution used. Of particular interest, glycerol levels partially reflected the extent of hepatocellular damage and liver enzyme release. Glycerol levels partially discriminated preservation of different quality and were in accordance to histological findings and liver enzyme release. Lactate, pyruvate, and glucose levels were not appropriate as markers during cold storage. Whether or not glycerol monitoring could represent an additional and rational complementation to the current practice of macroscopic, microscopic and donor evaluation has to be clarified by further studies.

Adenosine↗
PubMed2006

Retrograde reperfusion via vena cava lowers the risk of initial nonfunction but increases the risk of ischemic-type biliary lesions in liver transplantation--a randomized clinical trial.

Initial nonfunction (INF) and biliary complications such as ischemic-type biliary lesion (ITBL) remain two major complications in clinical orthotopic liver transplantation (OLT). The influence of ischemia and reperfusion injury (I/R) as a significant risk factor for both complications is widely unquestioned. A new reperfusion technique that reduces I/R injury should lead to a reduction in both INF and ITBL. One hundred and thirty two OLT patients were included in this study and randomized into two groups. Group A underwent standard reperfusion with anterograde simultaneous arterial and portal reperfusion and group B received retrograde reperfusion via the vena cava before sequential anterograde reperfusion of portal vein and hepatic artery. Serum transaminase level as a surrogate parameter for I/R injury and serum bilirubin level as a parameter for graft function were significantly reduced during the first week after OLT in group B. INF rate was 7.7% in group A and 0% in group B (P = 0.058). ITBL incidence was 4.55% in group A versus 12.3% in group B (P = 0.053). Retrograde reperfusion seemed to be beneficial for hepatocytes, but was detrimental for the biliary epithelium. The unexplained increased incidence of ITBL after retrograde reperfusion will be focus of further investigation.

Adult↗
PubMed2006

A very low toxic agent induces apoptosis and reduces growth of human hepatocellular carcinoma cells.

AIM: To examine the efficacy on growth inhibition of 2-methoxyestradiol (2-ME) on human hepatocellular carcinoma in vitro. METHODS: Hep3B, SK-Hep1, and PLC/PRF/5 cells were used. Proliferation assays using 2-ME should show a dose-dependent reduction of cell number. Different staining methods in cells derived from human hepatocellular carcinoma and normal human hepatocytes were performed to demonstrate possible tumor specific induction of apoptosis. FACS-analysis was done to confirm the induction of apoptosis after treatment with 2-ME. RESULTS: A reduction of the cell number of 90-98% was observed in all cancer cells after treatment with 2 micromol 2-ME. The mechanism of action appeared to be induction of apoptosis. Normal human hepatocytes were unaffected by 2-ME. The most sensitive cell line to 2-ME, SK-Hep1, showed an up-regulation of the p53 and p21 proteins. CONCLUSIONS: 2-Methoxyestradiol appears to be highly effective in reducing tumor growth in vitro in human hepatocellular carcinoma. It may be tumor specific and applicable for clinical trials.

2-Methoxyestradiol↗
PubMed2006

Immune reactivity is more suppressed in patients with alcoholic liver disease than in patients with virus-induced cirrhosis after CRH stimulation.

BACKGROUND: The most frequent diagnoses for liver transplantation are virus-induced cirrhosis (VIC) and alcoholic liver disease (ALD), after an abstinence period of at least 6 months. Chronic ethanol consumption has been linked to an abnormal neuroendocrine-immune axis and to an altered surgical stress response inducing an increased infection rate. Preoperative stress testing might be relevant to detect stress-induced immune alteration. The aim of this study was to investigate the preoperative stress-like response to corticotrophin-releasing-hormone challenge (CRH) of patients with ALD compared with patients with VIC and their immune sequelae. METHODS: Nine patients with ALD and 8 patients with VIC were included in this clinical study prior to transplantation. All patients received CRH in the morning. Blood samples were drawn before and after stress testing. RESULTS: In response to CRH, the ALD patients showed a significant decrease in the plasma interleukin (IL)-6/IL-10 ratio. After lipopolysaccharide stimulation of whole blood from CRH-challenged ALD patients, IL-10 increased significantly. The cytotoxic T1-(Tc1) to cytotoxic T2 (Tc2) ratio was significantly decreased in ALD patients after the stress test. Infections occurred significantly more often in ALD patients within the past year before study inclusion. CONCLUSIONS: ALD patients showed a stronger anti-inflammatory immune status and response than VIC patients. This difference was associated with a higher infection rate despite a median alcohol abstinence time of 3.5 years. Although an altered immune response is well known among patients with actual alcohol-use disorders, to the best of our knowledge, it is not described in patients after such a long abstinence time.

Adrenocorticotropic Hormone↗
PubMed2005

Liver transplantation for Budd-Chiari syndrome: A European study on 248 patients from 51 centres.

BACKGROUND/AIMS: The results of liver transplantation for Budd-Chiari syndrome (BCS) are poorly known and the role and timing of the procedure are still controversial. The aim of this study was to investigate the results of transplantation for BCS, focusing on overall outcome, on prognostic factors and on the impact of the underlying disease. METHODS: An enquiry on 248 patients representing 84% of the patients transplanted for BCS in the European Liver Transplantation Registry between 1988 and 1999. RESULTS: Of the 248 patients, 70.4% were female and 29.6% male. The mean age was 35.7 years. The overall actuarial survival was 76% at 1 year, 71% at 5 years and 68% at 10 years. 77% of deaths occurred in the first 3 months: 47% were due to infection and multiple organ failure, and 18% to graft failure or hepatic artery thrombosis. Late mortality (>1 year) occurred in nine patients, due to BCS recurrence in four of them. The only pre-transplant predictors of mortality on multivariate analysis (Cox) were impaired renal function and a history of a shunt. CONCLUSIONS: Liver transplantation for BCS is an effective treatment, irrespective of the underlying cause, and should be considered before renal failure occurs.

Adult↗
PubMed2005

Human hepatocytes are protected from ethanol-induced cytotoxicity by DADS via CYP2E1 inhibition.

We investigated the protective effects of diallyl disulfide (DADS), a potent inhibitor of cytochrome P450 2E1 (CYP2E1), on ethanol-induced toxicity in human hepatocytes. We found a clear dose-dependent response between ethanol and CYP2E1 activity. The ethanol-dependent CYP2E1 enzyme activity and protein expression, lactate dehydrogenase and aspartate transaminase release, malondialdehyde formation and caspase-3 activity decreased dramatically in the presence of DADS. Furthermore, DADS increased the hepatocellular glutathione (GSH) content and prevented the ethanol-dependent cellular GSH depletion. Our data show that DADS reduces ethanol-induced toxicity in human hepatocytes by reducing CYP2E1 activity and/or stabilizing the cellular GSH content, which might be of therapeutic interest.

Allyl Compounds↗
PubMed2005

Megacolon in adulthood after surgical treatment of Hirschsprung's disease in early childhood.

Hirschsprung's disease (HD) is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel. However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of HD in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient's bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify HD patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage.

Adult↗
PubMed2005

Extended indications in living-donor liver transplantation: bile duct cancer.

The advantages of living donor liver transplantation are an individually available graft and a tremendously reduced waiting time until transplantation. One consequence is that many centers have extended the pretransplant selection criteria, especially for potential recipients suffering from hepatocellular carcinoma. In contrast, reports on living donor liver transplantation for cholangiocarcinoma are restricted to few case reports. We have analyzed our experience with seven patients suffering from cholangiocarcinoma (Klatskin tumors, n=5; intrahepatic cholangiocarcinoma, n=2). During a median follow-up of 20 months (range 2-46 months), all patients are alive except for one posttransplant death. Four patients suffering from Klatskin tumors are alive without recurrence; both patients suffering from intrahepatic cholangiocarcinoma are alive with bone and peritoneal metastases. Living donor liver transplantation may be beneficial in selected patients suffering from Klatskin tumors, whereas caution should prevail when considering intrahepatic cholangiocarcinoma.

Bile Duct Neoplasms↗