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Biomedical subjects

R Neuhaus

Publications and source records attributed to R Neuhaus.

At least 19 recordsLinked to original sources

Acute renal failure after liver transplantation: incidence, etiology, therapy, and outcome.

Acute renal failure (ARF) was a frequent complication after orthotopic liver transplantation (OLT) when ARF was defined by a calculated glomerular filtration rate decrease of >50% or by a doubled serum creatinine above 2.5 mg/dL within the first week after OLT. We analyzed 1352 liver transplant recipients in retrospective fashion with regard to the incidence, etiology, therapy, and outcome of ARF; 162 patients developed ARF within the first week after OLT (12%), among whom 157 patients (97%) were recompensated by postoperative day 28. Altogether 52 patients (32%) received an average of 6 hemodialysis treatments, excluding the 5 patients (3%) who developed end-stage renal failure. Risk factors for this complication included hepatorenal syndrome type II, a glomerular filtration rate of <50 mL/min, and a diagnosis of hepatitis C.

Acute Kidney Injury↗

Primary immunosuppression with tacrolimus after liver transplantation: 12-years follow-up.

The early safety and efficacy of tacrolimus after liver transplantation has been shown in two multicenter trials. Herein, we report our single-center long-term follow-up of a randomized controlled trial. As part of a European multicenter trial, 121 patients entered the study at our institution and were randomly assigned to receive either tacrolimus and steroids (n=61) or a quadruple protocol (n=60) using ciclosporin A, steroids, azathioprine, and antithymocyte globulin (ATG). Twelve-year figures of patient survival were 74% in the tacrolimus group and 66% in the cyclosporine-based group. Graft survival after 12 years was 69% in the tacrolimus group compared to 56% in the cyclosporin-based group (not significant, p=0.15). The total rate of graft loss and retransplantation decreased significantly in the tacrolimus arm (p<0.05). De novo malignancies increased significantly in the ciclosporin-based group and dominated as single cause of death beyond 5 years posttransplant. The use of tacrolimus after liver transplantation resulted in a decreased rate of graft loss over the long-term. An increased number of de novo malignancies in the ciclosporin-based group may be attributable to the use of ATG as induction therapy.

Administration, Oral↗

Incidence of oral, pharyngeal, and laryngeal squamous cell carcinomas among 1515 patients after liver transplantation.

The purpose of this study was to evaluate the incidence and basic characteristics of oral, pharyngeal, and laryngeal squamous cell carcinomas (OPLC) in a single-centre series of liver transplantations (LT). The medical records of 1515 LT cases with a median follow-up of 6 years were analysed retrospectively for incident cases of OPLC. Incidence rates for the oral cavity and pharynx (ICD-9: 141-149), and larynx (ICD-9: 161) were assessed separately. OPLC cases and non-cases were evaluated with regard to end-stage alcoholic liver disease (ALD) as LT indication, smoking, and immunosuppression. The cumulative incidence of 13 cases with OPLC was 0.86% in total (n=1515). For 11 cases of OPLC in 307 patients with LT for ALD, it was 3.58%. The estimates for the annual incidence of OPLC (ICD-9: 141-149) were 121.79 for females and 111.65 for males (/100.000 patient-years). For OPLC (ICD-9: 161), the estimate was 37.21 for males, respectively (no female cases). ALD (84.6%) and pre-LT smoking (92.3%) were significantly overrepresented in OPLC cases (p<0.001). Age and gender distribution were comparable to non-cases. The 5-year survival rate after OPLC was 41.5%. OPLC were demonstrated as a late-onset complication of LT with poor prognosis. The impact of pre-, post-LT smoking, and, in particular, ALD as a confounder of OPLC deserves further investigation.

Adult↗

Withdrawal of steroids: a randomized prospective study of prednisone and tacrolimus versus mycophenolate mofetil and tacrolimus in liver transplant recipients with autoimmune hepatitis.

The aim of this study was to evaluate the success of steroid (PRED) withdrawal due to replacement by mycophenolate mofetil (MMF) in orthotopic liver transplant (OLT) recipients with autoimmune hepatitis (AIH). Thirty patients with AIH > 12 months after OLT randomized to receive either PRED and tacrolimus (TAC) or MMF and TAC were followed for 24 months. Withdrawal of steroids showed no difference regarding graft and patient survival. Also we demonstrated significantly lower glucose levels with lower HbA1c and a reduced need for insulin as well as a significantly lower serum cholesterol in the MMF group. Patients without steroids showed a lower incidence of osteopenia. Maintenance therapy in OLT patients with AIH may be performed safely using MMF instead of prednisone.

Adult↗

The influence of late acute rejection episodes on long-term graft outcome after liver transplantation.

Acute cellular rejection represents the most important single risk factor for the occurrence of chronic rejection after organ transplantation. We correlated late acute rejections with the occurrence of chronic graft failure after liver transplantation. We followed 1426 liver transplants for late acute rejection episodes defined as occurring >3 months after OLT. The overall incidence of chronic rejection in our patient population was 3.7%. In summary, we observed a predictive increase of transaminase levels prior to routine biopsies among patients with histologic evidence of late acute rejections. In contrast to other organ systems, late acute rejection episodes were not associated with the occurrence of chronic graft deterioration in liver grafts.

Acute Disease↗

Combination prophylaxis with Hepatitis B immunoglobulin and lamivudine after liver transplantation minimizes HBV recurrence rates unless evolution of pretransplant lamivudine resistance.

BACKGROUND: Survival rates of hepatitis B patients after liver transplantation improved significantly by introduction of passive immunoprophylaxis. Due to viral escape mutations recurrence still occurs, but recently a combination prophylaxis with hepatitis B immunoglobuline plus lamivudine is evaluated in transplant centers in terms of a further reduction of recurrence rates. PATIENTS AND METHODS: Between 1996 and 2000 a postoperative combination prophylaxis with HBIg and lamivudine was initiated in 44 HBsAg positive liver transplant recipients. In total 14 patients were HBV-DNA negative and 30 were HBV-DNA positive at the time of evaluation. In 22 HBV-DNA positive patients a pre-operative lamivudine treatment (150 mg/die) was started. Five of them developed pre-transplant lamivudine resistance with high viral replication (mean HBV-DNA prior to transplantation 728 +/- 219 pg/ml). In all patients passive immunoprophylaxis was started in the anhepatic phase with application of 10.000 units hepatitis B immunoglobuline. It was continued after seroconversion to HBsAg negativity with an aimed titer of more than 100 U/l and only stopped in case of HBV recurrence. Lamivudine was also continued indefinitely after liver transplantation. RESULTS: Overall recurrence rate in the 44 patients, including retransplantations and patients with pretransplant lamivudine resistance, was 11.5 % under combination prophylaxis. Recurrence was seen only in one of 39 patients (2.6 %) without preoperative lamivudine resistance, in contrast 4 out of 5 patients (80 %) with pre-existing lamivudine resistance suffered from early hepatitis B recurrence. The single patient without preoperative lamivudine resistance, who developed recurrence was pre-transplant HBV-DNA negative without lamivudine treatment, but a postoperative seroconversion to negative HBsAg could not be achieved. The overall 3 year patient survival rate was 91 % in the study population. One patient, who was retransplanted with preoperative lamivudine resistance, died 4.5 months after retransplantation due to hepatitis B recurrence and sepsis, three other patients died for reasons not related to hepatitis B recurrence. Combination prophylaxis was well tolerated in all patients and no severe side effects were observed. CONCLUSION: Combination prophylaxis with hepatitis B immunoglobulin and lamivudine is safe and highly effective in prevention of HBV recurrence after liver transplantation, even in case of positive viral replication. In accordance with the results of other centers it should therefore be the standard regimen. However it fails in the majority of patients with preoperative evolution of YMDD mutations, in which the optimal management has to be determined yet. To minimize preoperative resistance formation universal preoperative antiviral treatment of HBV-DNA positive patients should be replaced by individualized indication for preoperative treatment.

Adult↗

Preoperative antiviral treatment and postoperative prophylaxis in HBV-DNA positive patients undergoing liver transplantation.

BACKGROUND: Despite passive immunoprophylaxis a significant number of patients, especially if hepatitis B virus (HBV) DNA is positive prior to transplantation, develop HBV recurrence. This number might be reduced by lowering viral replication pretransplant with antiviral agents and by postoperative combination of antiviral agents and passive immunoprophylaxis. PATIENTS AND METHODS: A total of 74 HBV-DNA positive patients who underwent liver transplantation between 9/88 and 4/00 were analyzed retrospectively. Before lamivudine or famciclovir were available, in total 40 patients did not receive any preoperative antiviral therapy. Since 11/93, 17 patients were treated with famciclovir 1500 mg daily, after 4/96 17 patients with lamivudine 150 mg daily prior liver transplantation. Posttransplant all patients received passive immunoprophylaxis aiming at a titer of more than 100 U/liter. In the 34 patients with preoperative antiviral therapy an additional prophylaxis with the respective antiviral agent was applied. RESULTS: Under preoperative famciclovir and lamivudine 30 and 71% of patients became HBV-DNA negative, respectively. Actuarial reinfection rate 2 years after liver transplantation was 48% without antiviral prophylaxis, which was not statistically different from 55% under perioperative famciclovir therapy. In contrast only 18% developed HBV recurrence under perioperative lamivudine treatment. During both antiviral regimens neither pre nor posttransplant severe side effects were observed. CONCLUSION: Perioperative application of famciclovir is not recommendable, whereas lamivudine seems to lower recurrence rates significantly. Whether the observed effect is due to pre- or postoperative application remains to be addressed in further studies. In addition the long-term course has to be awaited.

2-Aminopurine↗

Liver transplantation for treatment of intrahepatic Osler's disease: first experiences.

BACKGROUND: Intrahepatic Osler's disease with multiple arteriovenous malformations and high intrahepatic shunting may lead to secondary pulmonary hypertension followed by right-heart stress and insufficiency. Until now, therapy with arterial embolization, banding, or ligation of the hepatic arteries is still limited and provides unsatisfactory long-term results. Liver transplantation offers another therapeutic option. METHODS: We report on four patients with intrahepatic involvement of Osler's disease who were liver transplanted between 1995 and 1999. All patients suffered from restricted liver function and right-heart insufficiency with multiple cardiac decompensations. One patient received one course of embolization, and another received six courses of embolization and then banding of the main hepatic artery before transplantation. In both patients, the clinical symptoms improved for only a few months. RESULTS: All patients had high degrees of intrahepatic arteriovenous shunting, and cardiac output measurements were between 8.0 to 13.3 L/min preoperatively. Preoperative mean pulmonary artery pressure was between 24 to 35 mmHg. After liver transplantation, cardiac output and right-heart diameter decreased or normalized and pulmonary pressure reached the normal range after 2 months. All patients received tacrolimus and steroids for primary immunosuppression. In one case, temporary hemodialysis was necessary for 2 weeks after transplantation, but renal function recovered completely. After follow-up time of 12 to 65 months, all patients had normal graft function and good cardiopulmonary condition. CONCLUSIONS: Indication for liver transplantation should be considered in patients with intrahepatic Osler's disease, high arteriovenous shunting with right-heart stress, and restricted liver function before irreversible fixed pulmonary hypertension leads to severe right-heart insufficiency or failure. Our therapeutic regimen of early liver transplantation in the case of intrahepatic Osler's disease in four patients has promising results.

Aged↗

Rapid decline of antibodies after hepatitis A immunization in liver and renal transplant recipients.

BACKGROUND: Hepatitis A vaccine is safe and achieves good seroconversion rates in liver (LTX) and renal (RTX) transplant recipients. METHODS: A study was performed to determine the anti-hepatitis A virus (HAV) antibody decline in LTX and RTX patients, and in healthy controls who have been immunized with two doses of hepatitis A vaccine. RESULTS: LTX and RTX patients had a satisfactory seroconversion rate after complete immunisation. However, 2 years later they had experienced a much more rapid antibody decline than controls, and only 59% of LTX and 26% of RTX seroconverters showed titres above the cut-off level defined as protective. CONCLUSIONS: Patients on immunosuppressive therapy may not be adequately protected against hepatitis A a few years after vaccination and alternative vaccination schemes may have to be considered.

Cyclosporine↗

Comparison of famciclovir and lamivudine in the long-term treatment of hepatitis B infection after liver transplantation.

BACKGROUND: Preliminary results of short-term famciclovir and lamivudine therapy in patients with hepatitis B virus (HBV) infection after liver transplantation revealed promising results. In a retrospective study the efficacy of long-term treatment with these substances was compared. METHODS: A total of 53 HBV-infected adults (48 reinfections and 7 de novo infections) received antiviral treatment. A total of 32 of these patients were treated with famciclovir 3x500 mg, 20 of them were later switched to lamivudine. Fourteen patients received lamivudine, 150 mg/day orally, as first line therapy and 7 patients after failure of famciclovir-prophylaxis. Follow-up time was 8 to 62 months (mean 35 months). Response to therapy (HBV-DNA negative) was compared using Kaplan-Meier estimates. Potential influence factors (HBV-DNA and HBeAg pretransplant, HDV coinfection, pretreatment with famciclovir and immunosuppression) on treatment response were analyzed by log. Rank test (univariate); then a multivariate analysis (Cox multiple stepwise regression model) was applied. RESULTS: A total of 19 and 76% of the patients treated with famciclovir and lamivudine resp. became HBV-DNA negative; 0 and 24% HBsAg negative. Lamivudine was also effective as second line therapy. In a multivariate analysis of all 73 treatment courses, lamivudine treatment and HDV-coinfection were significant factors for better treatment response; regarding only the lamivudine group, negative HBeAg pretransplant was significant. Viral breakthrough after prolonged treatment occurred in 55% (lamivudine) to 80% (famciclovir) of treatment courses but was only accompanied by mild hepatitis. CONCLUSIONS: Lamivudine and famciclovir are potent drugs for the treatment of HBV-infection after liver transplantation. The antiviral capacity of lamivudine is superior even after pretreatment with famciclovir but after prolonged treatment viral breakthrough is often observed.

2-Aminopurine↗