Ribavirin-Induced Anemia in Hepatitis C Virus Patients Undergoing Combination Therapy

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

Ribavirin Induced Hemolytic Anemia In Patients Infected With Chronic Hepatitis C Virus

Objective: The objective of this study was to determine the ribavirin-induced hemolytic anemia in patients infected by chronic hepatitis c virus.Study Design: Descriptive Case series study.Place and Duration:  Gastroenterology Unit, Isra University Hospital, Hyderabad from 15-10-2014 to 15-04-2015.Methodology: Total 102 patients were included. Complete and relevant gastrointestinal and systemic examination was performed with special emphasis on anemia and its manifestations. Every patient was tested with hepatitis C antibodies, (HCV RNA PCR positive), pre-treatment hemoglobin levels, and at twelve weeks, twenty-four weeks, and at forty-eight weeks of ribavirin treatment and documented on structured questionnaire. The laboratory data were also collected by the researcher and pathologist. Hemoglobin levels were checked before and after start of ribavirin at 12 weeks 24, and 48 weeks.Results: The patient’s mean age was 41.68±11.91 years. 41.18% of patients diagnosed with hemolytic anemia. A significant proportion of hemolytic anemia was observed in middle-aged group (34–48years), P–value 0.033. Mean reduction of hemoglobin levels were observed after 12 weeks. No significant association of hemoglobin levels was observed, in those who received ribavirin for 12 and 48 weeks P value 0.295.Conclusion: Noticeable frequency of hemolytic anemia observed among HCV patients treated with ribavirin

Use of Hematopoietic Growth Factor in the Management of Hematological Side Effects Associated to Antiviral Treatment for Hcv Hepatitis

Haematological abnormalities are common during combination antiviral therapy for chronic hepatitis C. Although dose reduction or discontinuation can easily treat these side effects, they can adversely affect the efficacy of combination antiviral therapy reducing the likelihood of a sustained viral response (SVR). To avoid potentially diminishing a patient’s chance of response, many physicians have begun using growth factors off-label to manage anaemia and neutropenia in hepatitis C. Haematopoietic growth factors are generally well tolerated and they may be useful for managing haematological side effects of anti-HCV therapy improving patients’ quality of life. To date, the role and benefit of these agents during anti-HCV therapy and their positive impact on SVR have not conclusively determined in the published studies. However, the possibility of a benefit to individual outpatients remains, and an individualized approach is recommended. This review explores the incidence, clinical significance, and management of anaemia, neutropenia and thrombocytopenia associated with combination therapy for HCV infection

Pegylated interferon (alone or with ribavirin) for chronic hepatitis c in haemodialysis population

Background/Aims: Hepatitis C virus infection remains prevalent among patients undergoing long-term haemodialysis and has a detrimental impact on survival in this population. Antiviral therapy for chronic hepatitis C in haemodialysis patients is still a challenge to clinicians. The aim of the current study is to evaluate the efficacy and safety of therapy with pegylated interferon, alone or combined with ribavirin, for chronic hepatitis C among patients undergoing long-term hemodialysis. Methods: We conducted a retrospective, multicenter cohort trial with monotherapy (pegylated interferon) (n=21) or combined antiviral therapy (pegylated interferon plus ribavirin) (n=5) for chronic hepatitis C in patients undergoing long-term haemodialysis. Results: Sustained virological response was obtained in eleven (42%) patients. Seven (26.9%) patients interrupted prematurely the antiviral treatment due to serious side-effects, the most frequent cause of treatment withdrawal being hematological (n=3). HCV RNA load was lower in responder than non-responder patients, 5.44 (3.45; 6.36) vs. 5.86 (4.61; 6.46) log10 copies/mL, even if the difference was not significant (P=0.099). Blood transfusion requirement was greater in patients on combined antiviral therapy than those on pegylated interferon alone, 100% (5/5) vs. 0% (0/21), P=0.0001. No difference in sustained viral response occurred between patients on combined antiviral therapy and those on pegylated interferon monotherapy [40% (2/5) vs. 42.8% (9/21), P=0.90]. Conclusions: Results from this study showed that pegylated interferon alone or with ribavirin is unsatisfactory in terms of efficacy and safety. Prospective trials based on interferon-free regimens (i.e., sofosbuvir plus ribavirin or sofosbuvir plus daclatasvir) are under way in patients with hepatitis C receiving long-term hemodialysis