Predictors of Changes in Hemoglobin Levels in Patients with Chronic Hepatitis C Treated with Ribavirin Plus Pegylated Interferon-α
ABSTRACT Combination therapy with pegylated interferon (pegIFN)-α and ribavirin (RBV) for chronic hepatitis C virus (HCV) infection is associated with reduction in hemoglobin (Hb) concentrations and anemia. The aim of this study was to evaluate the magnitude and frequency of change in Hb and determine the predictive risk factors for Hb decrease during this therapy.
We enrolled 308 patients with chronic HCV infection who were receiving weekly subcutaneous pegIFN injection in combination with body weight-based oral RBV for 24 weeks. Clinical and virological characteristics were used for studying the predictors of decrease in Hb.
The majority (95%) of patients showed reduction in Hb concentration of at least 1 g/dL during pegIFN and RBV combination therapy. The mean and median maximal decrease in Hb level of the study patients was 3.9 g/dL (range -0.3 to 8.2 g/dL; interquartile range 2.8-5.0 g/dL). Of all patients, 49.4% showed a reduction in Hb level of more than 4 g/dL; a higher number of male patients than female patients showed an Hb decrease of >4 g/dL. Multivariate analysis of our data showed that older age, high baseline Hb concentration, high HCV RNA viral load, low estimated glomerular filtration rate (eGFR), and low platelet count were independent predictors of significant decline in Hb levels.
Patients with low eGFR before antiviral therapy may have an increased risk of RBV-related anemia and should be closely monitored. Clinician should consider the potential risk of significant reduction in Hb level according to eGFR while deciding the RBV dose.
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ABSTRACT: Combination therapy with the ribavirin (RBV) prodrug taribavirin (TBV) and pegylated interferon (PIFN) has produced lower rates of anaemia than with RBV and PIFN. Studies have demonstrated that the sharpest decline in viral load during TBV therapy occurs at Weeks 4 through 6, when TBV reaches steady-state blood levels. The current proof-of-concept study was conducted to examine whether first-order viral kinetics could be influenced by pre-dosing TBV to steady state before introducing PIFN. Therapy-naïve patients with chronic hepatitis C virus (HCV) genotype 1 (G1) were randomised to receive (i) TBV 600 mg BID monotherapy for 4 weeks followed by combination therapy with PIFN [pre-dosing arm (n = 23)] or (ii) TBV administered concurrently with PIFN [standard dosing arm (n = 19)]. More patients achieved undetectable virus or a ≥2-log(10) reduction of HCV RNA at Week 4 in the pre-dosing vs. the standard dosing arm [33% vs. 22% (P = 0.497)]. There was also a trend towards greater reduction in mean log(10) change in HCV RNA in the pre-dosing vs. the standard dosing arm, which was statistically significant at Day 1 [-0.34 ± 0.46 vs. 0.09 ± 0.32 (P < 0.003)] but not at other time points up to Week 24. No significant difference was observed in the rates of anaemia (haemoglobin <10 g/dL) between study arms (4.5% vs. 5.3%). Pre-dosing TBV prior to starting PIFN produces a trend towards improved efficacy although statistical significance was not reached in this small patient population. These results warrant larger clinical trials of TBV pre-dosing.Alimentary Pharmacology & Therapeutics 06/2012; 36(4):370-8. DOI:10.1111/j.1365-2036.2012.05188.x · 5.73 Impact Factor
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ABSTRACT: OBJECTIVE:To review the literature regarding current strategies for the management of anemia associated with treatment for chronic viral hepatitis C (HCV) in adults.DATA SOURCES:The MEDLINE/PubMed, EMBASE, and Cochrane databases were searched (January 1980-October 2012) for articles in English using the search terms anemia, ribavirin, dose reduction, erythropoietin stimulating agents, hepatitis C, HIV, liver transplant, telaprevir, and boceprevir.STUDY SELECTION AND DATA EXTRACTION:All relevant original studies, meta-analyses, systematic reviews, guidelines, and review articles were assessed for inclusion. References from pertinent articles were examined for additional content not found during the initial search.DATA SYNTHESIS:Standard of care for patients infected with HCV genotype 1 now requires a triple therapy regimen including an HCV NS3 protease inhibitor. These regimens lead to significantly higher rates of anemia compared to prior dual therapy regimens. Development of an optimal management strategy should begin with risk stratification. Ribavirin dose reductions have been recommended in the package inserts for the pegylated interferon products and studies have demonstrated the need for maintenance of 80% of the initial ribavirin dose to achieve optimal sustained virologic response (SVR) with dual therapy. The use of erythropoietin-stimulating agents has been shown to be effective for anemia caused by peginterferon and ribavirin without compromising SVR rates. Limited data have been published regarding the management of anemia with triple therapy; however, efficacy studies for boceprevir and telaprevir have used ribavirin dose reduction and erythropoietin-stimulating agents to successfully manage anemia.CONCLUSIONS:Anemia is a common adverse event associated with the use of ribavirin, and, more recently, the new HCV protease inhibitors. Ribavirin dose reduction should continue to be used as an initial anemia management strategy, with the use of erythropoietin alfa 40,000 units once weekly reserved for patients whose hemoglobin does not adequately respond to initial management strategies.Annals of Pharmacotherapy 02/2013; 47(2). DOI:10.1345/aph.1R513 · 2.06 Impact Factor
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ABSTRACT: Adding telaprevir to pegylated-interferon and ribavirin increased both response rates and side effects of hepatitis C virus (HCV) treatment. We identified variables associated with severe anemia during telaprevir-based triple therapy. An observational study was performed on 142 HCV-infected patients between June 2011 and March 2012. All subjects completed 12 weeks of telaprevir-based triple therapy or discontinued early due to anemia. Severe anemia was defined by a hemoglobin ≤8.9 g/dL; advanced fibrosis was determined by Fib-4 ≥3.25. The 47 (33%) patients who developed severe anemia were similar to those who did not in sex, race, and prior response to dual therapy, but they were more likely to have diabetes (23.4% vs. 6.3%, p<0.01), advanced fibrosis (46.8% vs. 29.5%, p=0.04), and a history of anemia during previous dual therapy (29.7% vs. 11.4%, p=0.02). Patients developing severe anemia were older (59 vs. 56 years, p=0.02), had lower baseline platelet counts (134 vs. 163 x10(9) /L, p=0.04), hemoglobin (14.0 vs. 15.0 g/dL, p<0.01), estimated glomerular filtration rate (79 vs. 90 mL/min/1.73m(2) , p=0.03), and a higher median ribavirin/weight ratio (14.9 vs. 13.2 mg/kg, p<0.01). In multivariable logistic regression, presence of diabetes (OR=5.61, 95%CI: 1.59-19.72), Fib-4 ≥3.25 (OR=3.09, 95%CI: 1.28-7.46), higher ribavirin/weight ratio (OR=1.31 per mg/kg, 95%CI: 1.13-1.52), and lower baseline hemoglobin (OR=0.57 per g/dL, 95%CI, 0.41-0.80) were independently associated with developing severe anemia. Severe anemia occurred in one-third of patients receiving telaprevir-based triple therapy. Risk was greater in patients with diabetes, advanced liver fibrosis, higher ribavirin/weight ratio and lower baseline hemoglobin. This article is protected by copyright. All rights reserved.Liver international: official journal of the International Association for the Study of the Liver 10/2013; 34(7). DOI:10.1111/liv.12342 · 4.85 Impact Factor