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Eberhard L Renner

Publications and source records attributed to Eberhard L Renner.

13 recordsLinked to original sources
PubMed2006

Lymph node enlargement during combination therapy for chronic hepatitis C with pegylated interferon alpha and ribavirin: harmless reaction or harmful disease?

BACKGROUND: Perihepatic lymph node enlargement (LNE) is often present in patients with chronic hepatitis C (CHC) and correlates with the degree of inflammation, as well as the stage of fibrosis of the liver. LNE at sites distant from the liver hilum, however, is not a common feature of chronic hepatitis but may occur during antiviral therapy as we report here. OBJECTIVES: The aim of this study was to examine the frequency and aetiology of LNE at sites distant from the liver hilum in patients with chronic hepatitis C during combination therapy with pegylated interferon alpha and ribavirin. METHODS: The charts of all patients undergoing therapy with PEG and RIBA for CHC at our institution from January 2002 to April 2003 were reviewed for those who developed de novo LNE at sites distant from the liver hilum. RESULTS: In total, 8/217 patients (3.7%) or 5/125 patients treated within clinical trials (4.0%) were recorded to have developed de novo LNE during antiviral therapy. CONCLUSION: LNE at various sites distant from the liver hilum was observed in up to 4% of our patients during treatment of CHC with PEG and RIBA. While being reactive in nature and resolving upon cessation of therapy in the majority of patients de novo LNE may be due to serious disease and warrants further investigations.

Adult↗
PubMed2006

HCV-related advanced fibrosis/cirrhosis: randomized controlled trial of pegylated interferon alpha-2a and ribavirin.

In patients with hepatitis C virus (HCV)-related advanced fibrosis/cirrhosis, 30% of sustained HCV clearance has been reported with pegylated interferon alpha-2a (PEG-IFN) alone, but the efficacy and tolerability of the PEG-IFN/ribavirin (RBV) combination remain poorly defined. A total of 124 treatment-naïve patients with biopsy proved HCV-related advanced fibrosis/cirrhosis (Ishak score F4-F6, Child-Pugh score < or =7) were randomized to 48 weeks of PEG-IFN (180 microg sc weekly) and standard dose of RBV (1000/1200 mg po daily, STD) or PEG-IFN (180 microg sc weekly) and low-dose of RBV (600/800 mg po daily, LOW). Sustained virologic response (SVR) rates with PEG-IFN/STD RBV (52%) were higher--albeit not significantly--than that with PEG-IFN/LOW RBV (38%, P = 0.153). In multivariate analysis, genotype 2/3 and a baseline platelet count > or =150 x 10(9)/L were independently associated with SVR. The likelihood of SVR was < 7% if viraemia had not declined by > or =2 log or to undetectable levels after 12 weeks. Nine adverse events in the STD RBV and 15 in the LOW RBV group were classified as severe (including two deaths); dose reductions for intolerance were required in 78% and 57% (P = 0.013), and treatment was terminated early in 23% and 27% of patients (P = n.s.). The benefit/risk ratio of treating compensated HCV-cirrhotics with STD PEG-IFN/RBV is favourable.

Adult↗
PubMed2006

Recurrent hepatitis C post-transplantation: where are we now and where do we go from here? A report from the Canadian transplant hepatology workshop.

Approximately 400 liver transplants are performed in Canada every year and close to 6000 per year in the United States. Forty per cent to 45% of all liver transplants are performed for patients with underlying hepatitis C virus (HCV)-related liver disease. These patients have a different natural history, new complication risks and different treatment efficacy than nontransplant HCV patients. Every effort must be made to identify those patients at highest risk for progressive liver disease post-transplant. Recurrent HCV is an Achilles' heel to transplant hepatology. The true natural history of this disease is only starting to unravel and many questions remain unanswered on the optimal management of these patients after liver transplantation. The present report summarizes the literature and ongoing research needs that are specific to HCV-related liver transplantation.

Canada↗
PubMed2004

Combination therapy with amantadine and interferon in naïve patients with chronic hepatitis C: meta-analysis of individual patient data from six clinical trials.

BACKGROUND/AIMS: In chronic hepatitis C, clinical trials evaluating the efficacy of amantadine (AMA) and interferon (INF) compared to INF monotherapy, have produced conflicting results. We performed a meta-analysis of the individual patient's data from previous studies. METHODS: Nine hundred and seventy-two patients from six European centres were evaluated by means of individual patient meta-analysis, using mixed models with centres and the centre-treatment interaction fitted as random variables. RESULTS: At the end of therapy, virological responses were 38.5% (95% CI 34.1-42.8) after INF and AMA, and 29.5% (95% CI 25.5-33.6) after INF alone (P = 0.003). Sustained response occurred in 111 (23.1%; 95% CI 19.3-20.2) and 85 patients (17.3%; 95% CI 14.0-20.7), respectively (P = 0.03). Even accounting for the centre effect, therapy with AMA and INF was more effective than IFN alone (P = 0.029). When genotypes and viraemia levels were combined, the response rate after combination therapy doubled that observed with IFN alone in all subgroups, except those with low viraemia and genotypes 2 or 3. CONCLUSIONS: In chronic hepatitis C, therapy with AMA and INF is effective and may be an alternative to INF and ribavirin in patients who cannot tolerate ribavirin.

Adult↗
PubMed2004

Immunosurveillance of alveolar echinococcosis by specific humoral and cellular immune tests: long-term analysis of the Swiss chemotherapy trial (1976-2001).

BACKGROUND/AIMS: Long-term chemotherapy with benzimidazoles is beneficial in non-resectable alveolar echinococcosis (AE). Criteria to track early therapeutic efficacy are lacking and the clinical impact of immunosurveillance is unsettled. We aimed to analyze this issue particularly for assessing the putative parasitocidal efficacy of chemotherapy. METHODS: The present study is part of our prospective Swiss trial outlined previously and comprises 57 patients with a median follow-up of 18.5 (3-30) years and with repeated tests of humoral and cell-mediated immunity. The series was subdivided into group A (n=23; curative surgery) and group B (n=34: non-resectable AE). RESULTS: Long-term survival was 87% (group A) and 76% (group B). The profiles of specific antibodies against EmII/3-10 antigen normalized within 3 years in most group A-patients, but remained above the cut-off value in 40% of group B-patients. This lack of normalization was associated with lower bioavailability of mebendazole. AE-recurrence after 'radical' surgery (up to 13 years) was associated with high anti-EmII/3-10 concentrations in 7 of 8 cases. Following abrogation of longterm chemotherapy in group B, no AE-recurrence occurred in 9/18 patients, suggestive of parasitocidal efficacy and documented by a normal EmII/3-10 profile. CONCLUSIONS: The EmII/3-10 profile is of value in monitoring AE after surgery and/or chemotherapy.

Adult↗
PubMed2003

Living donor liver transplantation and tolerance: a potential strategy in cholangiocarcinoma.

BACKGROUND: Donor-specific immune tolerance has been reported in isolated cases of kidney transplantation associated with bone marrow transplantation. The following is a description of a living donor liver transplantation for a hilar cholangiocarcinoma in a previous recipient of an allogeneic bone marrow transplant. METHOD: A right hemi-liver transplantation was performed using a liver allograft obtained from the same previous bone marrow donor. A neoadjuvant chemo-irradiation protocol was implemented before the procedure. Because of the presence of full chimerism, no immunosuppression has been necessary for the last 22 months. RESULTS: Liver graft function has remained excellent, and a magnetic resonance imaging scan at one and a half years has shown no tumor recurrence. A control liver biopsy at 1 year showed no rejection. CONCLUSIONS: Neoadjuvant chemo-irradiation therapy and removal of all immunosuppression after liver transplantation formed the basic structure of this approach. Additional benefits provided by living donor liver transplantation included limitation of tumor progression by diminishing the pretransplantation waiting time, radical excision of the tumor through a complete hepatectomy, and optimal timing of the transplant procedure within a neoadjuvant chemo-irradiation protocol.

Adult↗
PubMed2003

Twenty-four vs. forty-eight weeks of re-therapy with interferon alpha 2b and ribavirin in interferon alpha monotherapy relapsers with chronic hepatitis C.

BACKGROUND/AIM: Roughly 50% of patients with chronic hepatitis C, who relapsed after a previous monotherapy with interferon alpha, will respond in a sustained fashion to 24 weeks of re-therapy with the combination of interferon alpha plus ribavirin. Whether prolonging treatment duration to 48 weeks will further increase sustained response rates remains ill defined. In this randomised controlled pilot trial we compared the efficacy and tolerability of a 24 week with that of a 48 week course of combination therapy with interferon alpha and ribavirin in interferon monotherapy relapsers with chronic hepatitis C. METHODS: Interferon alpha monotherapy relapsers with chronic hepatitis C were randomised to receive interferon alpha 2b (3 x 3 MIU sc weekly) and oral ribavirin (1000/1200 mg po daily) for either 24 weeks or 48 weeks. Virological response was evaluated by HCV RNA PCR at week 10 (initial response), at the end of treatment (end of- treatment response) and at the end of 24 weeks follow-up (sustained response). Only patients with negative HCV RNA at week 10 continued treatment. Adverse events were recorded at regular intervals. RESULTS: Thirty-seven patients were enrolled, 19 (6 females, median age 43) in the 24 week and 18 (5 females, median age 40) in the 48 week treatment arm. Baseline characteristics were similar in both groups. At treatment week 10, 12/19 (63%) in the 24 week group and 14/18 (78%) patients in the 48 week group had lost HCV RNA in serum (p = 0.33). All initial responders remained HCV RNA negative throughout the treatment period. Sustained response rates were 10/19 (53%) in the 24 week group and 13/18 (72%) in the 48 week group (p = 0.31). Three patients discontinued treatment early (two due to moderate adverse events, one due to non-compliance). Dose modifications were necessary in 9 patients, 4 in the 24 week and 5 in the 48 week group for anaemia, neutropenia, nausea and depression, respectively. CONCLUSION: Prolonging interferon / ribavirin combination therapy in interferon alpha monotherapy relapsers with chronic hepatitis C from 24 to 48 weeks may increase sustained response rates. Larger controlled trials using pegylated interferon alpha and ribavirin in relapsers with chronic hepatitis C seem warranted.

Adult↗
PubMed2003

Evaluation of hepatitis B and hepatitis C virus-infected renal allograft recipients with liver biopsy and noninvasive parameters.

BACKGROUND: Patients with end-stage renal disease are at high risk for hepatitis B (HBV) or hepatitis C virus (HCV) infection. Because therapy indication for viral hepatitis depends on virologic, biochemical, and histologic criteria, liver biopsy usually is necessary. Recently, a panel of serum fibrosis markers has been postulated to allow quantification of liver fibrosis by noninvasive means. METHODS: A cross-sectional study of all hepatitis B surface antigen (HBsAg)- and anti-HCV-positive renal allograft recipients among 900 renal allograft recipients regularly controlled in the authors' outpatient nephrology service was performed. The correlation between histologic, biochemical, and virologic parameters was assessed with an emphasis on the fibrosis marker hyaluronate in this immunosuppressed population. RESULTS: Twenty-two HBsAg- and 62 anti-HCV-positive patients were analyzed. Based on polymerase chain reaction results, 86% of anti-HCV-positive and 95% of HBsAg-positive patients had actively replicating infection. In 41 of 67 (61%) patients with replicating disease, liver biopsy was performed, and the association of various biochemical parameters with the histologic scores for necroinflammation and fibrosis was investigated. Less than 10% of these patients had advanced fibrosis, although the mean time of infection was more than 15 years. We found no correlation of any of the serum parameters (including hyaluronate) with histologic activity of liver disease except for the peak glutamate-oxalacetate transaminase value recorded during the entire posttransplant period. CONCLUSION: Liver biopsy remains the gold standard for evaluation of liver disease and therapy decision in immunosuppressed renal allograft recipients.

Alanine Transaminase↗
PubMed2002

Living donor liver transplantation in patients with portal vein thrombosis: a survey and review of technical issues.

BACKGROUND: Unlike cadaveric liver transplantation, current attitudes in living donor liver transplantation (LDLT) quote increased risk factors in the potential recipient such as retransplantation, multiple previous surgeries, or preexisting recipient portal vein thrombosis (PVT) as absolute or relative contraindications to this procedure. METHODS: An international survey was performed to examine the attitude of transplant teams relative to LDLT in the setting of preexisting PVT in the potential recipient. A questionnaire was sent to a total of 80 transplant centers performing LDLT in the United States, Europe, Canada, Japan, Southeast Asia, and Australia. RESULTS: A response was obtained from 47 transplant centers (59% response rate). This included 2146 LDLT procedures that combined both left and right lobe allografts. The incidence of acute preexisting recipient PVT was 18 (0.8%) and of chronic PVT was 26 (1.2%). Thrombectomy was performed in 28 (64%), a jump graft in 13 (29.5%), and a combination of both thrombectomy and a jump graft in 2 (4.5%) cases. With reference to the presence of preexisting PVT in the potential recipient, 5 centers considered this to be an absolute contraindication (10.7%), 24 centers as a relative contraindication (51%), and 18 as not being a contraindication (38.3%) to LDLT. CONCLUSIONS: The overall response to our questionnaire reflected a cautious attitude within the transplant community. Ethical criteria pertaining to risk undertaken by a healthy donor in situations of higher recipient morbidity risk does seem to impact on the decision to undertake LDLT in this group of patients.

Health Surveys↗
PubMed2002

Cost-effectiveness of cadaveric and living-donor liver transplantation.

BACKGROUND: Cadaveric liver transplantation (5-year survival >80%) represents the standard of care for end-stage liver disease (ESLD). Because the demand for cadaveric organs exceeds their availability, living-donor liver transplantation has gained increasing acceptance. Our aim was to assess the marginal cost-effectiveness of cadaveric and living-donor orthotopic liver transplantation (OLT) in adults with ESLD. METHODS: Using a Markov model, outcomes and costs of ESLD treated (1) conservatively, (2) with cadaveric OLT alone, and (3) with cadaveric OLT or living-donor OLT were computed. The model was validated with published data. The case-based scenario consisted of data on all 15 ESLD patients currently on our waiting list (3 women, 12 men; median age, 48 years [range, 33-59 years]) and on the outcome of all OLT performed for ESLD at our institution since 1995 (n=51; actuarial 5-year survival 93%). Living-donor OLT was allowed in 15% during the first year of listing; fulminant hepatic failure and hepatocellular carcinoma were excluded. RESULTS: Cadaveric OLT gained on average 6.2 quality-adjusted life-years (QALYs) per patient compared with conservative treatment, living-donor OLT, an additional 1.3 QALYs compared with cadaveric OLT alone. Marginal cost-effectiveness of a program with cadaveric OLT alone and a program with cadaveric and living-donor OLT combined were similar (E 22,451 and E 23,530 per QALY gained). Results were sensitive to recipient age and postoperative survival rate. CONCLUSIONS: Offering living-donor OLT in addition to cadaveric OLT improves survival at costs comparable to accepted therapies in medicine. Cadaveric OLT and living-donor OLT are cost-effective.

Adult↗
PubMed2002

Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial.

Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment-naive patients with chronic hepatitis C yielded contradictory results. We therefore conducted a large, double-blind, placebo-controlled, multicenter trial in naive patients with chronic hepatitis C: 246 patients were randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks, then 3 MIU sc thrice weekly) and either amantadine sulphate (2 x 100 mg p.o. QD) or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum polymerase chain reaction (PCR) had fallen below detection limit (1,000 copies/mL) at treatment week 10, and stopped otherwise. All patients were followed for 24 weeks off therapy. After 10 weeks of treatment, 66/121 patients treated with amantadine (55%) and 78/125 treated with placebo (62%) had lost HCV-RNA (n.s.). After 24 weeks of follow-up, 25 patients in the amantadine (21%) and 17 (14%) in the placebo group remained HCV-RNA negative (n.s.). During therapy, virologic breakthroughs occurred less often in the amantadine than in the placebo group [14 (12%) vs. 27 (22%) patients; P =.04]. Multivariate logistic regression analysis revealed genotype, viremia level, age, and amantadine therapy [risk ratio 0.4 (95%CI 0.2-1.0), P =.05] as predictors of sustained virologic response. Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients. Compared with current standard treatment (interferon/ribavirin), the interferon/amantadine combination was not cost-effective. In conclusion, amantadine does not add to a clinically relevant extent to the treatment of naive patients with chronic hepatitis C.

Adult↗
PubMed2002

Simulation of hepatitis C based on a mandatory reporting system.

OBJECTIVE: Hepatitis C is a major cause of liver disease in European countries. We aimed to assess the current and future disease burden of hepatitis C. SETTING: A representative data set of hepatitis C was applied to a validated computer model. METHODS: The mandatory reporting of positive hepatitis C virus (HCV) test results by all medical laboratories in Switzerland and the clinical data obtained by questionnaire for each positive test from the treating physicians created a unique, representative epidemiological database allowing the determination of the age distribution of acute (i.e. newly acquired) and chronic HCV infections. Based on these data and a simulation model of the natural history of hepatitis C, we estimated the prevalence of HCV infection, future morbidity/mortality from cirrhosis/hepatocellular carcinoma and costs. RESULTS: Our analysis estimates a prevalence of anti-HCV in Switzerland of 1.25-1.75%, which is slightly higher than prior reports (0.5-1%) derived by extrapolation from selected populations. Although new HCV infections decreased after 1990, our analysis predicts that HCV-related morbidity and mortality will increase by 70-90%, reaching a maximum in 2015-2020, largely from complications in cases already prevalent in 1998. The model predicts that the incidence of cirrhosis will begin to decrease after 2005-2010. Antiviral treatment reduces disease burden by approximately 5%. Undiscounted HCV-related annual direct costs will more than double and reach a maximum of almost US$33 million in 2020. CONCLUSIONS: The incidence of HCV-related cirrhosis is predicted to decrease after 2005-2010, while disease burden and costs due to complications are estimated to continue to increase until 2015-2020.

Adolescent↗