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Backgroud: Cytokine response against hepatitis C virus (HCV) is likely to determine the natural course of infection as well as the outcome of antiviral treatment. However, the role of particular cytokines remains unclear. The current study analyzed activation of cytokine response in chronic hepatitis C patients undergoing standard antiviral treatment.Methods: Twenty-two patients were treated with pegylated interferon and ribavirin. Twenty-six different cytokine transcripts were measured quantitatively in peripheral blood mononuclear cells (PBMC) before and after therapy and correlated with therapy outcome as well as with clinical and liver histological data.Results: We found that patients who achieved sustained virological response (SVR) showed higher pretreatment cytokine response when compared to subjects in whom therapy was unsuccessful. The differentially expressed factors included IL-8, IL-16, TNF-α, GM-CSF, MCP-2, TGF-β, and IP-10. Serum ALT activity and/or histological grading also positively correlated with the expression of IL-1α, IL-4, IL-6, IL-10, IL-12, IL-15, GM-CSF, M-CSF, MCP-2 and TGF-β.Conclusion: Pretreatment activation of the immune system, as reflected by cytokines transcripts upregulation, positively correlates with treatment outcome and closely reflects liver inflammatory activity. [ABSTRACT FROM AUTHOR]

Background: Hypervariable region 1 (HVR1) contained within envelope protein 2 (E2) gene is the most variable part of HCV genome and its translation product is a major target for the host immune response. Variability within HVR1 may facilitate evasion of the immune response and could affect treatment outcome. The aim of the study was to analyze the impact of HVR1 heterogeneity employing sensitive ultra-deep sequencing, on the outcome of PEG-IFN-α (pegylated interferon α) and ribavirin treatment. Methods: HVR1 sequences were amplified from pretreatment serum samples of 25 patients infected with genotype 1b HCV (12 responders and 13 non-responders) and were subjected to pyrosequencing (GS Junior, 454/Roche). Reads were corrected for sequencing error using ShoRAH software, while population reconstruction was done using three different minimal variant frequency cut-offs of 1%, 2% and 5%. Statistical analysis was done using Mann–Whitney and Fisher’s exact tests. Results: Complexity, Shannon entropy, nucleotide diversity per site, genetic distance and the number of genetic substitutions were not significantly different between responders and non-responders, when analyzing viral populations at any of the three frequencies (≥1%, ≥2% and ≥5%). When clonal sample was used to determine pyrosequencing error, 4% of reads were found to be incorrect and the most abundant variant was present at a frequency of 1.48%. Use of ShoRAH reduced the sequencing error to 1%, with the most abundant erroneous variant present at frequency of 0.5%. Conclusions: While deep sequencing revealed complex genetic heterogeneity of HVR1 in chronic hepatitis C patients, there was no correlation between treatment outcome and any of the analyzed quasispecies parameters. [ABSTRACT FROM AUTHOR]

A correction to the article "The correlation between pretreatment cytokine expression patterns in peripheral blood mononuclear cells with chronic hepatitis c outcome" by Tomasz Laskus and colleagues published in a 2015 issue is presented.

Background: Hypervariable region 1 (HVR1) contained within envelope protein 2 (E2) gene is the most variable part of HCV genome and its translation product is a major target for the host immune response. Variability within HVR1 may facilitate evasion of the immune response and could affect treatment outcome. The aim of the study was to analyze the impact of HVR1 heterogeneity employing sensitive ultra-deep sequencing, on the outcome of PEG-IFN-α (pegylated interferon α) and ribavirin treatment., Methods: HVR1 sequences were amplified from pretreatment serum samples of 25 patients infected with genotype 1b HCV (12 responders and 13 non-responders) and were subjected to pyrosequencing (GS Junior, 454/Roche). Reads were corrected for sequencing error using ShoRAH software, while population reconstruction was done using three different minimal variant frequency cut-offs of 1%, 2% and 5%. Statistical analysis was done using Mann-Whitney and Fisher's exact tests., Results: Complexity, Shannon entropy, nucleotide diversity per site, genetic distance and the number of genetic substitutions were not significantly different between responders and non-responders, when analyzing viral populations at any of the three frequencies (≥1%, ≥2% and ≥5%). When clonal sample was used to determine pyrosequencing error, 4% of reads were found to be incorrect and the most abundant variant was present at a frequency of 1.48%. Use of ShoRAH reduced the sequencing error to 1%, with the most abundant erroneous variant present at frequency of 0.5%., Conclusions: While deep sequencing revealed complex genetic heterogeneity of HVR1 in chronic hepatitis C patients, there was no correlation between treatment outcome and any of the analyzed quasispecies parameters.