Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients A. Bruchfeld, 1 K. Lindahl, 2 O. Reichard, 2 T. Carlsson 2 and R. Schvarcz 2 Departments of 1 Renal Medicine and 2 Infectious Diseases, Karolinska University Hospital Huddinge and Solna, Karolinska Institute, Stockholm, Sweden Received March 2005; accepted for publication April 2005 SUMMARY. Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in combination with ribavirin. There is limited experience with either drug in dialysis [end stage renal disease (ESRD)]. Six haemodialysis patients, four with HCV genotype 1, one with genotype 4 and one genotype 2 were treated with pegylated interferon-alfa-2b (n ¼ 4) and pegylated interferon-alfa-2a (n ¼ 2) for 24–48 weeks according to genotype with a dose of 50 or 135 lg/week respectively. All patients were given reduced ribavirin doses, initially 200–400 mg/day. Ribavirin trough plasma con- centrations were measured with a HPLC method previously developed for earlier treatment studies, aiming at a target concentration of 10–15 lmol/L. Interferon related side-ef- fects were common, in one patient peg-alfa-2b was perma- nently reduced to 50 lg every 9–10 days with improvement in tolerance. Average ribavirin dose was 170–300 mg/day. Ribavirin-induced anaemia was treated with high doses of erythropoietin and low doses of iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR neg- ative during treatment which was completed or nearly completed in four patients. One patient terminated therapy prematurely due to pronounced interferon related side-ef- fects and another died of myocardial infarction probably not related to therapy. Three patients have remained HCV-RNA negative with extended follow-up, two of whom have had a successful kidney transplant. Pegylated interferons are likely to become a valuable addition for HCV therapy in ESRD and are possible to combine with ribavirin. However the phar- macokinetics and tolerability of both peg-alfa-2a and 2b need to be studied more closely in prospective studies before definite dosing recommendations can be made. Keywords: anaemia, dialysis, erythropoietin, hepatitis C, pegylated interferon, ribavirin. INTRODUCTION Hepatitis C is a prevalent infection in patients with end stage renal disease (ESRD). The prevalence, however, shows a considerable variation of 3–80% between countries and centres [1]. Several studies have found a detrimental effect of hepatitis C virus (HCV) on patients and graft survival after kidney transplantation [2,3]. The main medical complica- tions are an increased risk of severe infection, liver disease, de novo glomerulonephritis with or without cryoglobulinaemia and diabetes [4–6]. As a result of these potential risks of HCV in the kidney transplanted patient, the current recommendation is to give antiviral therapy before transplantation with the objective to eradicate the infection [7]. Apart from the benefit of reducing the risk of worsening liver disease re- cent studies have found that successful therapy can pre- vent de novo glomerulonephritis and diabetes after transplantation [8,9]. Two separate meta-analysis have found that interferon- alpha can be effective in 26–37% of HCV infected dialysis patients. However a fairly high drop-out rate of 30–37% was noted [10,11]. Ribavirin has been considered to be contra- indicated if creatinine clearance is lower than 50 mL/min due to a lack of knowledge regarding dosing and side-effects i.e. anaemia. We have however in recent studies shown that ribavirin in combination with interferon is possible to use in ESRD and in patients with reduced renal function. This, however, requires reduced ribavirin doses as well as close monitoring of side-effects. Ribavirin plasma monitoring is also recommended [12,13]. Ribavirin-induced anaemia can be handled with high-dose erythropoietin and adequate iron stores for erythropoeisis. Pegylated interferon, currently available as pegylated interferon-alpha-2a (PegasysÒ 40 kDa; Roche Diagnostics, Indianapolis, IN, USA) or pegylated interferon-alpha-2b (PegIntronÒ 12 kDa; Schering-Plough, Kenilworth, NJ, Abbreviations: ALT, alanine aminotransferase; ESRD, end stage renal disease; HCV, hepatitis C virus. Correspondence: Annette Bruchfeld, K 56, Division of Renal Medicine, Department of Clinical Science, Karolinska University Hospital/Huddinge, 141 86 – Stockholm, Sweden. E-mail: annette.bruchfeld@klinvet.ki.se Journal of Viral Hepatitis, 2006, 13, 316–321 doi:10.1111/j.1365-2893.2005.00680.x Ó 2005 Blackwell Publishing Ltd