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Low dose ribavirin for treatment of hepatitis C virus infected thalassemia major patients; new indications for combination therapy.

ABSTRACT: BACKGROUND:Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients. OBJECTIVES:Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far. PATIENTS AND METHODS:Two hundred eighty thalassemia patients with detectable HCV-RNA PCR (? 50 IU/mL) and liver histology consistent with chronic HCV infection were self-assigned to receive peginterferon alfa-2a (n = 81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n = 199). Treatment experienced patients were eligible for this study. RESULTS:Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51 % vs. 38 % P = 0.02). In multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95 % CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin < 2006 ng/mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load < 600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8 %). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin. CONCLUSIONS:According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.

SUBMITTER: Tabatabaei SV

PROVIDER: S-EPMC3412553 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Low dose ribavirin for treatment of hepatitis C virus infected thalassemia major patients; new indications for combination therapy.

Tabatabaei Seyed Vahid SV Alavian Seyed Moayed SM Keshvari Maryam M Behnava Bita B Miri Seyyed Mohammad SM Karimi Elizee Pegah P Zamani Farhad F Amini Kafiabad Sedigheh S Gharehbaghian Ahmad A Hajibeigy Bashir B Lankarani Kamran Bagheri KB

Hepatitis monthly 20120630 6

<h4>Background</h4>Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients.<h4>Objectives</h4>Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far.<h4>Patients and methods</h4>Two hundred eighty thalassemia patients with detectable HCV-RNA PCR ( ...[more]

PMID: 22879826

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Project description:The current standard of care for hepatitis C virus (HCV) infection - combination therapy with pegylated interferon and ribavirin - elicits sustained responses in only ?50% of the patients treated. No alternatives exist for patients who do not respond to combination therapy. Addition of ribavirin substantially improves response rates to interferon and lowers relapse rates following the cessation of therapy, suggesting that increasing ribavirin exposure may further improve treatment response. A key limitation, however, is the toxic side-effect of ribavirin, hemolytic anemia, which often necessitates a reduction of ribavirin dosage and compromises treatment response. Maximizing treatment response thus requires striking a balance between the antiviral and hemolytic activities of ribavirin. Current models of viral kinetics describe the enhancement of treatment response due to ribavirin. Ribavirin-induced anemia, however, remains poorly understood and precludes rational optimization of combination therapy. Here, we develop a new mathematical model of the population dynamics of erythrocytes that quantitatively describes ribavirin-induced anemia in HCV patients. Based on the assumption that ribavirin accumulation decreases erythrocyte lifespan in a dose-dependent manner, model predictions capture several independent experimental observations of the accumulation of ribavirin in erythrocytes and the resulting decline of hemoglobin in HCV patients undergoing combination therapy, estimate the reduced erythrocyte lifespan during therapy, and describe inter-patient variations in the severity of ribavirin-induced anemia. Further, model predictions estimate the threshold ribavirin exposure beyond which anemia becomes intolerable and suggest guidelines for the usage of growth hormones, such as erythropoietin, that stimulate erythrocyte production and avert the reduction of ribavirin dosage, thereby improving treatment response. Our model thus facilitates, in conjunction with models of viral kinetics, the rational identification of treatment protocols that maximize treatment response while curtailing side effects.

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Low dose ribavirin for treatment of hepatitis C virus infected thalassemia major patients; new indications for combination therapy.

Publications

Low dose ribavirin for treatment of hepatitis C virus infected thalassemia major patients; new indications for combination therapy.

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