Molecular characterization of hepatitis C virus in end‐stage renal disease patients under hemodialysis

Abstract

New direct-acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end-stage renal disease patients on hemodialysis (ESRD-HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment-naïve patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD-HD patients presented HCV genotypes 1a (n = 18), 1b (n = 16), 2a (n = 2), 2b (n = 2), and 3a (n = 4). Control subjects were infected with genotypes 1a (n = 11), 1b (n = 21), 2b (n = 4), and 3a (n = 8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD-HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD-HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms.

Hepatitis C in Hemodialysis Units: diagnosis and therapeutic approach

“…28 Another point of concern is the phenomenon of intermittent viremia, which is not only epidemiological, but also an inconvenience in the control of nosocomial transmission, since the results can be misinterpreted, classifying a patient with active infection as non-virememic. 18,20,29,30 The use of molecular tests with low detection levels should always be recommended.…”

Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis

“…Cytotoxic T lymphocytes and natural killer cells are necessary for the control of viral infection. A functional exhaustion of antiviral lymphocytes is reported in COVID-19 patients (Zheng et al, 2020a;Alves da Silva et al, 2018). However, there is still limited evidence for the predictive role of lymphocyte count in predicting the severity of COVID-19.…”

Prevalence of resistance-associated substitutions to direct-acting antiviral agents in hemodialysis and renal transplant patients infected with hepatitis C virus

“…Treatment-induced viral resistance can be defined as the positive selection of viral variants with reduced susceptibility to DAAs. 40 The presence of naturally occurring RASs to DAAs has been reported in patients from Europe, the US and Japan, while there are few studies demonstrating naturally occurring GT1 mutations in Latin America.…”

“… 44 Another paper from our group demonstrated that HCV genome variability and number of mutations were higher in HD patients when compared to non-HD patients. 40 …”