Ribavirin in chronic hepatitis C: past and future

Loustaud‐Ratti, Véronique; Rousseau, Annick; Marquet, Pierre; Denis, François; Alain, Sophie

doi:10.1586/eri.09.5

Cited by 7 publications

(8 citation statements)

References 44 publications

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“…Its mechanism of action is based on the erroneous incorporation of ribavirin triphosphate into replicating RNA strands, thereby inhibiting chain elongation[24]. When used with interferon, ribavirin acts synergistically, preventing relapses and breakthroughs, and remains relevant in the DAA era in special circumstances.…”

Section: Pharmacokinetics Of Hcv Treatmentsmentioning

confidence: 99%

“…The results obtained did not differ between alpha interferon and pegylated alpha interferon[106]. Ribavirin is generally contra-indicated in patients with eGFR values of less than 50 mL/min due to the high risk of ribavirin metabolite accumulation in erythrocytes, which increases the amplitude of hemolytic anemia[24,107]. However, at minimal doses, ribavirin was used after each dialysis session[108] or 5 d per week[109].…”

Section: Experiences On Anti-hcv Therapies In Populations At Renal Riskmentioning

confidence: 99%

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Anti-hepatitis C virus drugs and kidney

Carrier

Essig

Debette-Gratien

et al. 2016

WJH

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Hepatitis C virus (HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease (CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in end-stage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents (DAAs) while avoiding peginterferon and ribavirin. The first results were convincing. To aid in the correct use of these drugs in patients with renal insufficiency, their pharmacokinetic properties and potential renal toxicity must be known. The renal toxicity of these new drugs was not a safety signal in clinical trials, and the drugs are generally efficient in these frail populations. These drugs are usually well tolerated, but recent cohort studies have demonstrated that these new regimens may be associated with renal side effects, especially when using sofosbuvir combinations. HCV, renal diseases and comorbidities are intimately linked. The close monitoring of renal function is required, particularly for at-risk patients (transplanted, HIV-coinfected, CKD, hypertensive or diabetic patients). New DAA regimens, which will soon be approved, will probably change the landscape.

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Section: Pharmacokinetics Of Hcv Treatmentsmentioning

confidence: 99%

Section: Experiences On Anti-hcv Therapies In Populations At Renal Riskmentioning

confidence: 99%

Anti-hepatitis C virus drugs and kidney

Carrier

Essig

Debette-Gratien

et al. 2016

WJH

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“…Studies have shown that guanosine supplementation can counter RBV-induced toxicity by restoring host GTP pools (33). Although IMPDH inhibition cannot completely account for RBV's antiviral activity, the addition of guanosine can increase cell health through restoration of nucleotide pool balance (32,33). Therefore, infections were performed in the RBV S cells in the presence of equimolar con- centrations of RBV and guanosine.…”

Section: Rbv R Huh75 Cells With Reduced Rbv Uptakementioning

confidence: 99%

Host-Based Ribavirin Resistance Influences Hepatitis C Virus Replication and Treatment Response

Ibarra

Jain

Pfeiffer

2011

J Virol

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Many individuals infected with hepatitis C virus (HCV) develop a chronic infection, and of those who are treated with pegylated interferon and ribavirin (RBV), many do not respond. While the nucleoside analog RBV improves treatment outcome, and will likely be an important component of therapy with next-generation viral inhibitors, RBV's mechanism is controversial. Most of RBV's proposed mechanisms require RBV import into cells. Therefore, we explored whether host-based RBV resistance develops through reduced cellular uptake, akin to chemotherapy resistance in some cancers. We examined the effect of host-based RBV resistance on HCV replication in cultured hepatoma Huh7.5 liver cells and whether RBV resistance develops in HCV patients. When Huh7.5 cells were exposed to RBV, resistance developed through reduced RBV uptake via the ENT1 nucleoside transporter and antiviral efficacy was reduced. The uptake defect in RBV-resistant cells was specific to RBV, since transport of another ENT1 substrate, cytidine, was unaffected. Importantly, RBV uptake significantly declined in HCV patient peripheral blood mononuclear cells (PBMCs) following 4 weeks of therapy. Furthermore, maintenance of RBV uptake correlated with rapid treatment response. Our results uncovered a novel form of antiviral drug resistance and suggest that host-based RBV resistance develops in HCV patients undergoing therapy and that maintenance of RBV uptake may contribute to rapid viral clearance.

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“…Hepatitis C viral (HCV) infection is a major cause of chronic liver diseases, whose current treatment is a combination of antiviral therapy of pegylated interferon-α and ribavirin (RBV). − However, several factors, such as the high cost of therapy, several months of treatment, and side effects, contribute to low patient compliance, and above all, anemia, due to the drug accumulation into red blood cells, are the main reason of RBV treatment interruptions . Thus, for attenuating liver injury, inhibiting hepatitis viral replication but to reduce hemolysis, RBV should ideally be delivered to the liver, especially to hepatocytes .…”

Section: Introductionmentioning

confidence: 99%

Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes

et al. 2013

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Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment.

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Ribavirin in chronic hepatitis C: past and future

Cited by 7 publications

References 44 publications

Anti-hepatitis C virus drugs and kidney

Anti-hepatitis C virus drugs and kidney

Host-Based Ribavirin Resistance Influences Hepatitis C Virus Replication and Treatment Response

Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes

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