Biomedical subjects

Peter Neuhaus

Publications and source records attributed to Peter Neuhaus.

At least 73 records · Page 4Linked to original sources

PubMed2005

Changing impact of cytomegalovirus in liver transplantation -- a single centre experience of more than 1000 transplantations without ganciclovir prophylaxis.

As cytomegalovirus (CMV) disease was a leading cause of death following liver transplantation in earlier reports, general CMV prophylaxis is widely used. We re-evaluated the impact of CMV in a recent time period under balanced immunosuppression and effective CMV diagnostics and therapy. A retrospective analysis of 1200 liver transplantations between 1988 and 2000 was performed comparing the incidence of CMV infection and disease and patient survival rates in two different time periods (before and after availability of the pp65-antigenaemia assay). In addition, risk factors for CMV in the recent time period were analysed. No ganciclovir prophylaxis was administered during the whole study period. The incidence of CMV tissue invasive disease decreased from 9.4% in period I to 2.7% in period II, whereas the incidence of viral syndrome was about 6% in both periods. Especially CMV pneumonia and generalized disease were almost abandoned in period II. Patients with tissue invasive disease, but not with infection or viral syndrome had reduced survival rates in both periods. However, the disease-specific mortality was 10% and 0% respectively. The overall rate of CMV infection in period II was low (25.9%). Risk factors for CMV infection in the univariate analysis were: Initial nonfunction, D+R- seroconstellation, acute liver failure, triple or quadruple immunosuppression, OKT3 or ATG treatment, transfusion of >10 packed red cells, steroid boluses, postoperative mechanical ventilation and retransplantation. In the multivariate analysis only quadruple or triple immunosuppression, OKT3-treatment, transplantation for acute liver failure and initial nonfunction. The incidence of CMV tissue invasive disease as well as the disease-specific mortality has markedly decreased during the last years. Using routine surveillance with the pp65-antigenaemia assay, CMV infection and disease rates compare well to data with long-term ganciclovir prophylaxis. As D+R- patients still more often develop symptomatic disease, pre-emptive therapy could be useful in this patient group.

Antibodies, Viral↗

PubMed2005

Coronary event rates in liver transplant recipients reflect the increased prevalence of cardiovascular risk-factors.

Increased prevalence of cardiovascular risk-factors in liver transplant recipients compared with pretransplant and standard population data has been acknowledged. The impact of risk-profiles on cardiovascular event rates or death, however, has not yet been established. Here we evaluate the development of risk-factors during a prospective follow-up of 10 years in 302 patients and compare numbers of coronary events with data from the German Prospective Cardiovascular Münster (PROCAM)-Score population. Prevalence of overweight (17% vs. 27%), hypertension (70% vs. 80%), and diabetes (21% vs. 25%) increased from early to late after transplantation, while elevated serum cholesterol (64% vs. 37%) and triglycerides (40% vs. 21%) became less frequent. Cardiovascular risk-profiles favoring tacrolimus over ciclosporin A based immunosuppression early after transplantation converged over time. Increased risk-scores in liver transplant recipients matched with score standardized event rates in the PROCAM population (ratio: 1.11, 95% CI: 0.53-2.03), nine events were predicted for the transplant population and oppose 10 events observed. Thus, indicating a reflection of increased cardiovascular risk-profiles in corresponding numbers of cardiovascular events.

Adult↗

PubMed2005

Induction of long-term graft acceptance by a combination treatment of donor splenocytes and CTLA4Ig in a high responder rat liver transplantation model.

The CTLA4Ig has led to an improved survival rate in various allograft transplantation models. We investigated in a high responder rat model (Dark Agouti to Lewis) of orthotopic liver transplantation (ORLT), whether an additional adoptive cell transfer can enhance the effect of CTLA4Ig. After transplantation, recipients (n = 13/group) were treated with donor or third-party splenocytes alone or in combination with CTLA4Ig. Administration of splenocytes alone had no significant effect on survival (median 13 days, range 9-14) compared with untreated controls (median 10 days, range 8-12). CTLA4Ig monotherapy prolonged survival to a median of 30 days (range 11-150) but resulted in long-term graft rejection. The additional administration of third-party splenocytes showed no significant improvement over CTLA4Ig monotherapy. Only the combination of donor splenocytes with CTLA4Ig led to long-term graft acceptance (>150 days) without clinical and/or histological signs of rejection. A higher rate of apoptosis could be detected in livers at early time-points in long-term survivors receiving CTLA4Ig and donor splenocytes. Analysis of cytokine mRNA expression revealed a decrease of interleukin-2 at early time-points in all groups receiving CTLA4Ig; whereas, interferon-gamma was increased in long-term survivors receiving CTLA4Ig and donor cells or donor cells alone. The combination of CTLA4Ig and donor derived splenocytes is potent to induce long-term survival and graft acceptance. The mechanisms appear to involve the induction of an early inflammatory impulse and apoptosis.

Abatacept↗

PubMed2005

Preoperative evaluation of living kidney donors using multirow detector computed tomography: comparison with digital subtraction angiography and intraoperative findings.

To assess the accuracy of multirow detector computed tomography (MDCT) for the evaluation of renal anatomy for preoperative donor assessment in living related kidney transplantation. MDCT-scans (4- and 16-slice-CT) of 51 consecutive living kidney donors (age, 51.6 +/- 9.7 years; range, 28-68 years) were analysed by three blinded observers and compared with digital subtraction angiography (DSA) and surgery. Contrast-enhanced MDCT was performed with 1 mm slice thickness reconstruction interval during arterial and venous phases. Supernumerary renal arteries, veins, early branching of vessels and abnormalities of the ureters were documented. The overall accuracy of computed tomography angiography (CTA) for detection and classification of surgically relevant arterial variants was 97% (99/102). The interpretation of 16-channel MDCT images was correct in all cases (accuracy, 100%), while the four-channel CTA had three incorrect results regarding the differentiation of early branching vessels from double renal arteries (accuracy, 93%). The overall accuracy of DSA was 91%. Renal vein abnormalities were correctly diagnosed with MDCT in 100% compared with 89% correct findings with DSA. There were three kidneys with incomplete ureter duplication, detected both with MDCT and DSA. MDCT demonstrated superior accuracy compared with non-selective DSA for the preoperative assessment of renal anatomy in living kidney donors; and for the distinction of supernumerary arteries versus early branching patterns, 16-channel CTA data were better than those of the four-channel system.

Adult↗

PubMed2005

Major influence of oxygen supply on 13CO2:12CO2 ratio measurement by nondispersive isotope-selective infrared spectroscopy.

BACKGROUND: The nondispersive isotope-selective infrared spectroscopy (NDIRS) is a valid method for the measurement of the 13CO2:12CO2 ratio in breath samples. Methodical influences have to be considered to obtain valid results. AIM: To evaluate the effect of oxygen supply to patients on the measurement of 13C:12C ratio in breath samples by NDIRS. METHODS: Breath samples of 26 healthy volunteers were taken before, immediately after, and 5 minutes after inhalation of 100% oxygen via a continuous positive air pressure (CPAP) mask. Analysis of breath samples was performed by NDIRS. RESULTS: Delta per thousand before oxygen inhalation was -25.8 +/- 0.2. Immediately after 5 minutes of 100% oxygen inhalation, delta per thousand increased to -14.8 +/- 0.5 (delta over baseline [DOB] 11.0 +/- 0.4) and after additional 5 minutes of room air inhalation, delta per thousand normalized to -25.6 +/- 0.2 (DOB 0.2 +/- 0.1). CONCLUSIONS: Oxygen supply to patients and, therefore, changes in gas composition in breath samples clearly influence 13CO2 measurement by NDIRS. This has to be taken into account in the clinical setting. Thus, oxygen supply during measurement of exhaled 13CO2 by NDIRS has to be avoided or maintained at a strictly constant level.

Adult↗

PubMed2005

"Blogs" and "wikis" are valuable software tools for communication within research groups.

Appropriate software tools may improve communication and ease access to knowledge for research groups. A weblog is a website which contains periodic, chronologically ordered posts on a common webpage, whereas a wiki is hypertext-based collaborative software that enables documents to be authored collectively using a web browser. Although not primarily intended for use as an intranet-based collaborative knowledge warehouse, both blogs and wikis have the potential to offer all the features of complex and expensive IT solutions. These tools enable the team members to share knowledge simply and quickly-the collective knowledge base of the group can be efficiently managed and navigated.

Communication↗

PubMed2005

In vitro evaluation of the transportability of viable primary human liver cells originating from discarded donor organs in bioreactors.

BACKGROUND: The use of primary human liver cells obtained from discarded donor organs is increasingly favored for cell-based extracorporeal liver support systems. However, as cryopreservation of primary human hepatocytes causes a significant loss of metabolic activity, the transport of bioreactors with viable liver cells is required. The aim of this study was to evaluate the impact of two major potential threats to viable cells during transport: temperature changes and mechanical stress. METHODS: In each experiment three hollow fiber-based bioreactors were charged with primary human liver cells originating from the same discarded donor organ and were simultaneously kept under culture conditions for 8 days. In total, 18 bioreactors were evaluated. On the fifth day the bioreactors were exposed to hypothermia (4 degrees C, n = 3), to hyperthermia (42 degrees C, n = 3), or served as normothermic controls (37 degrees C, n = 3). In a second test series bioreactors were exposed to vibration (21 Hz for 20 min, thereafter 7 Hz for 160 min, n = 3), or were operated as control cultures (n = 6). The release of hepatocyte-specific enzymes was determined as an indicator for cell damage. RESULTS: Hypothermic stress resulted in a significant release of transaminases and led to disturbances of the histological integrity, all indicating a high degree of cell damage. When compared with the control cultures, hyperthermia and mechanical stress in terms of vibration had no significant effect on the cells. CONCLUSION: The transport of hollow fiber bioreactors charged with viable primary human liver cells appears to be feasible in transport monitors for perfusion and temperature control.

Bioreactors↗

PubMed2005

The SlideReactor--a simple hollow fiber based bioreactor suitable for light microscopy.

Most bioartificial liver support systems are based on hollow fiber capillaries within modified dialysis cartridges or more sophisticated bioreactor constructions. Due to their design microscopic follow-up of reorganization and growth of tissue between the hollow fibers is not possible. The SlideReactor is a simple hollow fiber based bioreactor construction suitable for light microscopy and time-lapse video observation. The SlideReactor offers a cell compartment separated from a medium inflow and outflow compartment. Cell compartment access ports enable easy filling of the cell compartment with cell suspension, as well as fixation of the tissue. For more complex procedures or full access to all the cells, the bioreactor can be opened easily by cutting the silicone seal with a scalpel. Due to its simple design and the utilization of standard materials, it could serve as a suitable, cost-efficient tool to evaluate the behavior of cells cultured between hollow fiber capillaries. The paper describes the production process: similar to open source projects in software engineering, we would like to propose the concept as an open platform to anyone interested in hollow fiber based cell culture.

Bioreactors↗

PubMed2005

Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation--a randomized, double-blind trial.

Bacterial infections frequently occur early after liver transplantation. We recently reported significant progress with a synbiotic composition, consisting of one lactic acid bacteria (LAB) and one fiber, which reduced the infection rate from 48% (with selective bowel decontamination) to 13%. Now, our aim is to study if a combination of different LAB and fibers would further improve outcome. A prospective randomized double-blind trial was undertaken in 66 liver transplant recipients. All patients received enteral nutrition immediately post-operatively. Comparison was made between one group (A) receiving a composition of four LAB and four fibers and another group (B) receiving the fibers only. The treatment started the day before surgery and continued for 14 days. Thirty-day infection rate, length of hospital stay, duration of antibiotic therapy, non-infectious complications and side effects of enteral nutrition were recorded. The incidence of post-operative bacterial infections was significantly reduced; being 48% with only fibers and 3% with LAB and fibers. In addition, the duration of antibiotic therapy was significantly shorter in the latter group. In both groups, mainly mild or moderate infections occurred. Fibers and LAB were well tolerated. Early enteral nutrition supplemented with a mixture of LAB and fibers reduces bacterial infection rates following liver transplantation. Treatment with only fibers led to a low incidence of severe infections.

Anti-Bacterial Agents↗

PubMed2005

In vivo imaging of human pancreatic microcirculation and pancreatic tissue injury in clinical pancreas transplantation.

Pancreatitis remains to be a major complication following clinical pancreas transplantation. We performed orthogonal polarized spectral (OPS) imaging for direct in vivo visualization and quantification of human pancreatic microcirculation in six healthy donors for living donor liver transplantation and 13 patients undergoing simultaneous pancreas-kidney transplantation. We further determined the impact of microvascular dysfunction during early reperfusion on pancreatic graft injury. Exocrine and endocrine pancreatic impairment was determined by analysis of serum lipase, amylase and C-peptide levels. Compared to normal pancreas in liver donors (homogeneous acinar perfusion) functional capillary density (FCD) and capillary red blood flow velocity of reperfused grafts were significantly decreased. Elevated CRP concentrations on day 2 post-transplant and serum lipase and amylase levels determined on days 4-5 significantly correlated with microvascular dysfunction during the first 30 min of graft reperfusion. Post-transplant serum C-peptide also correlated significantly with pancreatic capillary perfusion. OPS imaging allows to intra-operatively assess physiologic pancreatic microcirculation and to determine microcirculatory impairment during early graft reperfusion. This impairment correlated with the manifestation of post-transplant dysfunction of both exocrine and endocrine pancreatic tissue. OPS imaging may be used clinically to determine the efficacy of interventions, aiming at attenuating microcirculatory impairment during the acute post-transplant reperfusion phase.

Adult↗

PubMed2005

MMF and calcineurin taper in recurrent hepatitis C after liver transplantation: impact on histological course.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is almost universal. The optimal immunosuppression for these patients is still under discussion. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) treatment in patients with recurrent hepatitis C. Forty patients with histologically proven hepatitis C recurrence after OLT were treated with MMF and calcineurin inhibitor (CNI) taper for 24 months and matched with 40 non-MMF-treated positive liver transplant recipients. Liver biopsies were obtained prior to MMF treatment and after a mean follow-up of 24 months. Histological changes were evaluated utilizing the Metavir score. Comparison of fibrosis/inflammation showed no impairment of histological findings during MMF treatment. In contrast, histological findings of the 40 non-MMF patients showed a significant increase of severity for inflammation/fibrosis. Viral load was similar in both groups. The course of alanin amino transferase (ALT) levels measured during MMF treatment showed a significant decrease. MMF in combination with CNI taper showed a positive effect on fibrosis progression, graft inflammation and ALT levels and may improve the clinical course of HCV after OLT, however, the antiviral properties of MMF are still unconfirmed.

Calcineurin Inhibitors↗

PubMed2005

Hepatic resection in liver transplant recipients: single center experience and review of the literature.

Biliary complications such as ischemic (type) biliary lesions frequently develop following liver transplantation, requiring costly medical and endoscopic treatment. If conservative approaches fail, re-transplantation is most often an inevitable sequel. Because of an increasing donor organ shortage and unfavorable outcomes in hepatic re-transplantation, efforts to prolong graft survival become of particular interest. From a series of 1685 liver transplants, we herein report on three patients who underwent partial hepatic graft resection for (ischemic type) biliary lesions. In all cases, left hepatectomy (Couinaud's segments II, III and IV) was performed without Pringle maneuver or mobilization of the right liver. All patients fully recovered postoperatively, but biliary leakage required surgical revision twice in one patient. At last follow-up, two patients presented alive and well. The other patient with persistent hepatic artery thrombosis (HAT), however, demonstrated progression of disease in the right liver remnant and required re-transplantation 13 months after hepatic graft resection. Including our own patients, review of the literature identified 24 adult patients who underwent hepatic graft resection. In conclusion, partial graft hepatectomy can be considered a safe and beneficial procedure in selected liver transplant recipients with anatomical limited biliary injury, thereby, preserving scarce donor organs.

Adult↗

PubMed2005

[Living donor liver transplantation from the perspective of the donor: results of a psychosomatic investigation].

OBJECTIVES: Living donor liver transplantation (LDLT) has been gaining importance in the treatment of endstage liver disease in adults. Thus far, only few empirical studies have been published on the psychosocial situation of donors who are faced with the risk of medical complications after resection of the right hepatic lobe. The aims were to describe the clinical problems before and after transplantation and to contribute to the discussion of ethical issues based on empirical findings. METHODS: In the present overview, the pre-/post-transplant and follow-up periods are characterized from a psychosocial point of view using actual psychosocial and medical findings in living donors of the right hepatic lobe. RESULTS: Before LDLT, 11 % of potential donors were not recommended for the transplantation due to marked ambivalence about the operation. After donation 26 % of donors showed high values for anxious depression and physical complaints despite low rates of surgical complications. CONCLUSIONS: For clinical psychosomatic evaluations of potential donors it is important to provide donors an opportunity to report any misgivings and anxieties as openly as possible. The psychosocial impairment and physical complaints of some donors after transplantation are yet not clearly understood. More psychosocial studies in this field will be necessary to investigate ethical questions and to develop criteria for an evidence-based medical care of living donors.

Anxiety↗

PubMed2005

Monitoring of human cytomegalovirus, HHV-6 and HHV-7 infection in kidney transplant recipients by molecular methods to predict HCMV disease after transplantation: a prospective study.

OBJECTIVES: Recently, highly sensitive molecular assays to detect HCMV, HHV-6 and HHV-7 have been developed but their ability to detect patients at high risk for disease is unclear. METHODS: The positive predictive values (PPV) of pp65-antigenemia, quantitative plasma DNA and pp67-mRNA for CMV-disease were prospectively compared in 82 transplant recipients (72 renal, 10 pancreas-kidney) without CMV-prophylaxis. In addition, the prevalence of HHV-6 and HHV-7 infection were assessed using qualitative PCR. The assays were performed weekly. RESULTS: Three patients (3,7%) developed CMV-disease and were effectively treated. They were positive in all three CMV-assays. The PPVs of pp65-Ag, DNA viral load and pp67-mRNA were 33%, 20% and 25% in CMV-positive and 100%, 67% and 50% in seronegative recipients. Sensitivity and negative predictive value were 100% for all assays. Using cut-offs, PPVs were 75% (pp65-Ag > or = 20/200.000 cells) and 100% (PCR > or =30.000 copies/ml). Transfusion of >2 packed red cells, rejection and non-functioning graft were risk factors for CMV Five patients and one patient were positive for HHV-6 and HHV-7 resp.; both were symptomless and did not have a HCMV infection. CONCLUSIONS: Therefore, pp65-antigenemia and plasma PCR with a cut-off could be useful for monitoring preemptive therapy.

Cytomegalovirus↗

PubMed2004

Steroid administration before partial hepatectomy with temporary inflow occlusion does not influence cyclin D1 and Ki-67 related liver regeneration.

BACKGROUND AND AIMS: If temporary inflow occlusion is required during liver resection, the postoperative course might be complicated by ischaemia-reperfusion injury. Steroids protect against ischaemia-reperfusion injury; however, due to its anti-proliferative character concerns exist on its use on liver regeneration after resection. We investigated the effects of methylprednisolone on hepatocyte proliferation after partial hepatectomy with temporary inflow occlusion. PATIENTS AND METHODS: Prior to surgery, one group of Wistar rats received methylprednisolone, while a second group served as non-treated controls. Ischaemia-reperfusion injury was indicated by AST, ALT, and GLDH at 6 h after surgery. Immunohistochemistry tools were used to determine the mitotic index and Ki-67 expression, while cyclin D1 expression characterized the proliferative activity on days 1, 4, 7, and 10. RESULTS: The post-ischaemic liver enzyme release had significantly decreased in the methylprednisolone group, while expression of cyclin D1, percentage of Ki-67-positive cells, and mitotic cell index were comparable in both groups. Similar results were found for bilirubin and albumin and for weight of proliferating liver. CONCLUSION: Although steroid administration significantly reduced ischaemia-reperfusion-associated tissue injury, it has no apparent effects on hepatic regeneration. Thus, steroids could be recommended if a temporary liver ischaemia is required during surgery, in order to reduce complications caused by severe ischaemia-related organ dysfunction.

Animals↗

PubMed2004

Description of B lymphocytes and plasma cells, complement, and chemokines/receptors in acute liver allograft rejection.

BACKGROUND: Although antibody mechanisms play a pathogenetic role in liver allograft rejection, no data exist on B lymphocytes, plasma cells, complement, and chemokines in rejected liver tissue. METHODS: Liver biopsy specimens from 25 patients with acute allograft rejection (AR) (rejection activity index, RAI score: 1-9) were analyzed by immunohistochemistry (IH) and reverse transcriptase-polymerase chain reaction (RT-PCR) and compared with biopsy specimens taken prior to implantation (PI). The number of CD20 and CD138 cells was evaluated, and the presence and abundance of the chemokines macrophage inflammatory protein (MIP)-3alpha, CXCL9, CXCL10, CXCL11, CXCL12, and their receptors CCR-6, CXCR3, and CXCR4 were examined. Complement depositions were visualized by C4d IH. RESULTS: The numbers of B lymphocytes (P=0.002) and plasma cells (P=0.022) were significantly higher in AR biopsy specimens compared with PI biopsy specimens. MIP-3alpha and CCR-6 cells were detected in the portal fields of all AR biopsy specimens. IH double staining revealed a colocalization of MIP-3alpha/CD20 cells; C4d deposits could be demonstrated along the portal capillaries. All examined chemokines and receptors could be detected in normal liver tissue and in AR biopsy specimens by RT-PCR and semiquantitative RT-PCR, demonstrating an overexpression of CXCL10 and -11. CONCLUSIONS: The significant increase of B lymphocytes and plasma cells during acute rejection, together with the lack of a significant increase of proliferating cells, indicates that the migration of B lymphocytes and plasma cells-promoted by the expression of B-cell activating chemokines/receptors-plays a key role in acute liver rejection. The C4d deposits along the portal capillaries indicate a humorally mediated alloresponse caused by the accumulated B and plasma cells.

Acute Disease↗

PubMed2004

The effects of FK778 in combination with tacrolimus and steroids: a phase II multicenter study in renal transplant patients.

BACKGROUND: In animal and in vitro models, FK778 inhibits acute rejection, modifies vasculopathy, and shows anti-viral activity. We report first efficacy and safety data of FK778 in human kidney transplant recipients at two concentration-controlled ranges. METHODS: In a double-blind manner, 149 patients were randomized to a 12-week treatment with FK778 in combination with tacrolimus (Tac) and corticosteroids (S). Of the high-level group (H), 49 patients received 2 x 600 mg/day FK778 and continued on 150 mg/day, 54 patients of the low-level group (L) got 1 x 600 mg/day followed by 75 mg/day, and 46 patients received placebo (P). Subsequent FK778 doses were adjusted to trough levels of 100-200 microg/mL (H) and 10-100 microg/mL (L). The primary endpoint was the incidence of biopsy proven acute rejection (AR). RESULTS: In 93% of the patients in group L, targeted plasma trough levels were reached by Day 3; in half of the patients in group H, the targeted levels were reached by Day 9. Graft survival at week 16 was 89.7%, 88.8%, and 91.3%, and the incidences of AR were 26.5%, 25.9%, and 39.1% for groups H, L, and P. For the subgroup of patients in which target levels were reached by week 2, incidences were 7.7%, 27.1%, and 39.1%, respectively. Anemia, the most frequently reported adverse event especially in group H, was reversible. Mean total cholesterol and LDL-cholesterol levels were reduced during FK778 treatment compared with group P. CONCLUSION: FK778 is pharmacologically active, well-tolerated, and safe. To fully benefit from this promising new drug, FK778 dosing will be optimized in subsequent studies.

Acute Disease↗

PubMed2004

Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up.

BACKGROUND: Recurrence of hepatitis C (HCV) infection after orthotopic liver transplantation (OLT) in HCV-positive patients is almost universal. Severity of graft hepatitis increases during the long-term follow-up, and up to 30% of patients develop severe graft hepatitis and cirrhosis. However, there are still no clear predictors for severe recurrence. The aim of this study was to examine the 10-year outcome and risk factors for graft failure caused by HCV recurrence. METHODS: In a prospective analysis, 234 OLTs in 209 HCV-positive patients with a median age of 53 years were analyzed. Immunosuppression was based on cyclosporine A or tacrolimus in different protocols. Predictors for outcome were genotype, viremia, donor variables, recipient demographics, postoperative immunosuppression, and human leukocyte antigen (HLA) compatibilities. RESULTS: Actuarial 5-, and 10-year patient survival was 75.8% and 68.8%. Eighteen of 209 (8.7%) patients died because of HCV recurrence, which was responsible for 35.9% of the total 53 deaths. Significant risk factors for HCV-related graft failure in an univariate analysis were multiple steroid pulses, use of OKT3, and donor age greater than 40. However, in a multivariate analysis, multiple rejection treatments with steroids and OKT3 treatment proved to be significantly associated with HCV-related graft loss. CONCLUSIONS: The analysis of causes leading to graft failure in patients with HCV showed that HCV recurrence is responsible for one of three deaths in HCV-positive patients. Rejection treatment contributed significantly to an enhanced risk for HCV-related graft loss. New antiviral treatments, as well as adapted immunosuppressive protocols, will be necessary to further improve the outcome of HCV-positive patients after liver transplantation.

Adolescent↗