Introduction: Hepatitis C virus (HCV) infection is associated with increased mortality and morbidity in kidney transplant patients. The ability to establish a sustained viral response before renal transplant is important for these patients. Direct-acting antiviral agents can increase the sustained viral response in most patients with HCV infection. In this case series, we aimed to determine the efficacy and safety of a combined therapy of ombitasvir, paritaprevir, ritonavir, and dasabuvir with or without ribavirin in patients with HCV genotype 1 infection without cirrhosis and on hemodialysis who were awaiting deceased-donor kidney transplant.
Methods: Our study included eight male and two female HCV ribonucleic acid (RNA)-positive hemodialysis patients (mean age 50.7 ± 15 years, mean hemodialysis duration 14 ± 5.5 years, mean HCV duration 18 ± 3.7 years).
Findings: Three patients with genotype 1a received oral therapy with 12.5 mg ombitasvir, 150 mg paritaprevir, 7 5 mg ritonavir, and 250 mg dasabuvir plus 200 mg ribavirin for 12 weeks. Seven patients with genotype 1b received 12.5 mg ombitasvir, 150 mg paritaprevir, 75 mg ritonavir, and 250 mg dasabuvir without ribavirin treatment for 12 weeks. The sustained virologic response rate was 100% at 12 weeks after completion of antiviral treatment in both treatment groups. No serious adverse effects were observed in either treatment group. Five patients had constitutional symptoms such as nausea, anorexia, and fatigue. During the treatment period, hemoglobin, white cell blood count, thrombocyte, and ferritin levels were similar to pretreatment levels. Treatment did not affect weekly erythropoietin and monthly intravenous iron treatment doses.
Discussion: Direct-acting antiviral agents are safe and effective for generating a sustained viral response in HCV genotype 1-infected hemodialysis patients on kidney wait lists.
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Pharmaceutical Chemistry Department, Faculty of Pharmacy, Horus University, New Damietta, 34517, Egypt.
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Faculty of Computer and AI, Cairo University, Giza, Egypt.
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Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
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