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      Hepatitis C in Dialysed Patients – What Is the Current Optimal Treatment?

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          Abstract

          Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in the dialysis population. The problem is more pronounced after renal transplantation. It seems that immunosuppressive drugs facilitate HCV replication and accelerate hepatic lesions. Interferon is not recommended after renal transplantation because of the risk of acute rejection and graft dysfunction, and for this reason it is important to eradicate HCV RNA before transplantation. Prevention is the most important treatment measure. Good clinical practice together with screening of blood products and organs is of outstanding importance. Pegylated interferon (PEG-INF) and ribavirin are currently considered to be optimal therapy for HCV infection. Pegylation delays clearance of interferon, which leads to a more potent and longer antiviral effect. The two PEG-INF formulations (alfa-2a and alfa-2b) with different pharmacokinetic characteristics are currently available. Their clearance is reduced by almost 45% in patients with end-stage renal disease. Taken together with the high prevalence of adverse effects associated with the PEG-INF, an increased awareness of their use in dialysis patients is reasonable. There are few published studies on interferon and PEG-INF therapy in uremic patients. These studies confirm that the rate of response to different interferon formulations in dialysis is much higher than in the general population, but with a higher rate of adverse events. Ribavirin increases the response rate to treatment with PEG-INF. Great caution is warranted on its use in dialysis patients, whereas in patients with renal disease it accumulates and causes a dose-related haemolysis. Current results are encouraging but limited by a small number of patients and short follow-up. Multi-centre, controlled studies with longer follow-up are needed to establish an optimal protocol for the treatment of chronic HCV infection in dialysis patients.

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          Most cited references21

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          Hepatitis C and renal disease: an update.

          Hepatitis C is both a cause and a complication of chronic renal disease. Chronic infection with hepatitis C virus (HCV) can lead to the immune complex syndromes of cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN). The pathogenetic mechanisms for these conditions have not been defined, although they are clearly caused by the chronic viral infection. Management of HCV-related cryoglobulinemia and MPGN is difficult; antiviral therapy is effective in clearing HCV infection in a proportion of patients, but these conditions can be severe and resistant to antiviral therapy. Hepatitis C also is a complicating factor among patients with end-stage renal disease and renal transplants. The source of HCV infection in these patients can be nosocomial. Screening and careful attention to infection control precautions are mandatory for dialysis units to prevent the spread of hepatitis C. Prevention of spread is particularly important in these patients because HCV infection is associated with significant worsening of survival on dialysis therapy, as well as after kidney transplantation. Furthermore, therapy for hepatitis C is problematic, only partially effective, and associated with significant side effects in this population. There are significant needs in both basic and clinical research in the pathogenesis, natural history, prevention, and therapy for hepatitis C in patients with renal disease.
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            Epidemiology of hepatitis C virus among long-term dialysis patients: a 9-year study in an Italian region.

            Monitoring hepatitis C virus (HCV) antibodies (anti-HCV) in long-term dialysis patients is an important issue of public health. The aim of the study is to analyze the prevalence, seroconversion rate, and impact of HCV-positive serological test results on survival. We studied 6,412 patients starting long-term dialysis therapy reported to Lazio Dialysis Registry (Italy) between 1995 and 2003. HCV serological status was assessed by using second- or third-generation assays. Patients who were seronegative at the beginning of a period who became seropositive at the end of the same period are defined as seroconverters. In 1995 to 2003, the overall prevalence of anti-HCV among long-term dialysis patients decreased from 30.6% to 15.1%; we did not observe a decrease in prevalence of anti-HCV in those starting dialysis treatment. After a decrease in the first year, HCV seroconversion rates remained stable at approximately 2 cases/100 person-years. Survival at 9 years was lower for both HCV seroconverters and those already anti-HCV positive at dialysis therapy initiation compared with HCV-negative subjects (log-rank test, P < 0.001). Results of a multiple Cox model showed that subjects who were or became anti-HCV positive had a hazard ratio of 1.29 (95% confidence interval, 1.15 to 1.44) compared with HCV-negative patients. We did not observe a significant decrease in HCV seroconversion rates in 1995 to 2003. The overall decrease in anti-HCV prevalence could be related to the lower survival probability for both HCV seroconverters and those already HCV positive at long-term dialysis therapy initiation compared with HCV-negative subjects. Our findings confirm that additional efforts should be made to minimize the risk for HCV infection before and during long-term dialysis treatment.
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              Meta-analysis: interferon for the treatment of chronic hepatitis C in dialysis patients.

              The efficacy of interferon monotherapy in dialysis patients with chronic hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue. We evaluated the efficacy and safety of initial interferon monotherapy in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We have identified 14 clinical trials (269 unique patients); two were controlled studies. The mean overall estimate for sustained virological response (SVR) and drop-out rate was 37%[95% confidence interval (CI) 28-48] and 17% (95% CI 10-28), respectively. The most frequent side-effects requiring interruption of treatment were flu-like symptoms (17%), neurological (21%) and gastrointestinal (18%). The overall weighted estimate for SVR in patients with hepatitis C virus genotype 1 was 30.6% (95% CI 20.9-48). In the sub-group of clinical trials (n = 5) with standard interferon administration (3 million units [MUI] thrice weekly, subcutaneous route, 24-week treatment), the overall mean estimate of SVR was 39% (95% CI 25-56). The studies were heterogeneous with regard to SVR and drop-out rate. Tolerance to initial interferon monotherapy was lower in dialysis than nonuremic patients with chronic hepatitis C. However, more than one-third of haemodialysis patients with chronic hepatitis C have been successfully treated with interferon. Longer duration of interferon monotherapy does not appear to have a beneficial effect on the response rate. Further studies are warranted to define the optimal anti-viral regimen for chronic hepatitis C in dialysis population.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2007
                June 2007
                20 April 2007
                : 30
                : 3
                : 156-161
                Affiliations
                Department of Dialysis, Zagreb University Hospital Centre, Zagreb, Croatia
                Article
                101918 Kidney Blood Press Res 2007;30:156–161
                10.1159/000101918
                17446715
                e06e9688-eb39-438f-93bc-67f26c1ddb0f
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 03 February 2007
                Page count
                Tables: 2, References: 29, Pages: 6
                Categories
                Review

                Cardiovascular Medicine,Nephrology
                Interferon alfa,Ribavirin,Peginterferon,Dialysis,Hepatitis C,End-stage renal disease

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