Ribavirin treatment in dialysis patients with chronic hepatitis C virus infection – a pilot study

Abstract

Standard treatment for chronic hepatitis C is with interferon (IFN)-alpha and ribavirin for 6-12 months. In dialysis patients only interferon therapy is currently used due to the lack of knowledge concerning ribavirin dosage and side-effects. The aim of this study was to investigate if ribavirin can be added to interferon when treating dialysis patients with hepatitis C. Five patients on haemodialysis and one patient on peritoneal dialysis with chronic hepatitis C, five with genotype 1 and one with genotype 4, were given interferon-alpha2b 3 MU thrice weekly for 4 weeks, whereafter ribavirin 200-400 mg was added, for an intended total treatment period of 28 weeks. Ribavirin plasma concentrations were monitored, using HPLC. Four patients completed the treatment. One patient suffered marked side-effects from interferon and therapy was terminated. One patient developed heart failure and died after 14 weeks of treatment but the death was not considered treatment related. Based on plasma concentrations, ribavirin doses were frequently adjusted initially. The target concentration (10-15 micromol/L) was reached with average daily doses of 170-300 mg ribavirin. Ribavirin induced anaemia was managed with high doses of erytropoietin (20 000-30 000 IU/week). Five of six patients became hepatitis C virus (HCV)-RNA negative during treatment, but four relapsed post-treatment; one is HCV-RNA negative. Hence ribavirin, in combination with IFN-alpha, can be used to treat dialysis patients with HCV. However, this requires reduced ribavirin doses and close monitoring of ribavirin plasma concentrations and haemoglobin. Ribavirin-induced anaemia can be managed with high doses of erythropoeitin.

Understudied populations with hepatitis C

“…Nevertheless, attempts have been made to use low doses of ribavirin (200 mg daily or every other day) with interferon therapy in patients on dialysis, but anemia was still problematic and required intensive monitoring and erythropoietin therapy. 48 Studies of peginterferon therapy are currently under way in patients with varying degrees of renal insufficiency. Until there is more information on the safety and efficacy of peginterferon with or without ribavirin in patients with renal disease, these agents should be used with caution by investigators with experience in managing interferon side effects and preferably in the context of prospective trials.…”

Management of Hepatitis C Infection in Renal Transplant Recipients

“…This trial has demonstrated that, despite the impaired clearance of ribavirin in patients with renal dysfunction, the drug could still be used safely if its dose is reduced and if its plasma concentrations and hemoglobin levels are closely monitored (69). Treatment with ribavirin alone has failed to clear HCV RNA in renal transplant recipients, but has been found to cause a drop in HCV RNA titers by 70-82% in 57% of the patients, and has not been associated with any detrimental side-effects on graft function (70).…”

Meta‐analysis: interferon for the treatment of chronic hepatitis C in dialysis patients

“…Data on alternative therapeutic options, such as combination therapy with ribavirin, are even more preliminary in nature. [55][56][57] The optimal regimen for interferon monotherapy in dialysis patients with chronic hepatitis C remains poorly established. The primary goal of our study was to synthesize the available evidence on the tolerability and efficacy 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.…”