Remodeling of immunological biomarkers in patients with chronic hepatitis C treated with direct-acting antiviral therapy

Ribeiro, Isabela Gomes; Coelho-dos-Reis, Jordana Grazziela Alves; Fradico, Jordana Rodrigues Barbosa; Costa-Rocha, Ismael Artur da; Silva, Luciana Diniz; Fonseca, Lucy Ana dos Santos; Stancioli, Rhaissa Carvalho Said; Teixeira-Carvalho, Andréa; Martins‐Filho, Olindo Assis; Teixeira, Rosângela

doi:10.1016/j.antiviral.2021.105073

Cited by 8 publications

(8 citation statements)

References 24 publications

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“…When comparing cytokine levels in CHC patients and healthy individuals, we found that CHC patients showed lower levels of proinflammatory cytokine TNF-α, anti-inflammatory cytokine IL-10, Th2 cytokines (IL-4, IL-5 and IL-13), Th22 cytokines (IL-22) and Th9 cytokines (IL-9) before starting DAA treatment and after achieving SVR. This finding partially goes in line with a study showing significantly reduced concentrations of IL-5, IL-9 and IL-10 in patients with CHC compared to healthy controls [ 17 ]. In addition, Riberio et al suggested that lower levels of IL-5 could be a universal biomarker of DAA treatment and an important factor in the case of HCV re-infection [ 17 ].…”

Section: Discussionsupporting

confidence: 91%

“…This finding partially goes in line with a study showing significantly reduced concentrations of IL-5, IL-9 and IL-10 in patients with CHC compared to healthy controls [ 17 ]. In addition, Riberio et al suggested that lower levels of IL-5 could be a universal biomarker of DAA treatment and an important factor in the case of HCV re-infection [ 17 ]. Furthermore, Baskic et al showed that lower but sustained IL-4 production refers to Th2 predominance in higher stages of fibrosis [ 18 ].…”

Section: Discussionsupporting

confidence: 91%

“…Considering that CHC is generally characterised by a strong proinflammatory response, these findings provide more evidence for the potential inhibition of inflammatory mechanisms during DAA treatment of CHC patients. Notably, Riberio et al found elevated serum concentrations of IL-4, TNF-alpha, FGF, PDGF and GM-CSF in patients with CHC compared to healthy controls [ 17 ]. This discrepancy could potentially be attributed to higher age and higher fibrosis levels of patients analysed in the Brazilian study.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C

Radmanić

Bodulić

Simicic

et al. 2022

Viruses

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In this study, we evaluated the effect of hepatitis C virus eradication using direct-acting antivirals (DAA) on the serum cytokine and growth factor profiles of chronic hepatitis C patients (CHC). Serum concentrations of 12 cytokines and 13 growth factors were measured in 56 patients with CHC before, during the DAA treatment and after sustained virological response using bead-based flow cytometry. Cytokine and growth factor levels were also measured in 15 healthy individuals. The majority of the selected cytokines and growth factors exhibited similar concentrations before, during and after successful DAA treatment, the exceptions being IL-10, EGF, HGF and VEGF. Significantly lower concentrations of IL-10, IL-13, IL-4, IL-4, IL-9, TNF- α and higher levels of Ang-2, HGF and SCF were observed in patients with CHC before and after DAA treatment compared with healthy individuals. Patients with severe fibrosis stages exhibited higher levels of Ang-2 and lower levels of EGF, PDGF-AA and VEGF. Furthermore, IL-4, IL-5 and SCF were characterized as potential biomarkers of DAA treatment using random forest. Additionally, logistic regression characterized EGF as a potential biomarker of severe CHC. Our results suggest inhibition of pro-inflammatory processes and promotion of liver regeneration in CHC patients during DAA treatment.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C

Radmanić

Bodulić

Simicic

et al. 2022

Viruses

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“…Mechanistic study revealed that the combination treatment increased viral genome mutation rate compared to the monotherapy treatment ( 75 ). In addition, several studies have demonstrated prophylactic and therapeutic efficacy of the drug against influenza A and B virus infections in disease-relevant human airway epithelial models, mouse models, and ferret models ( 47 , 81 , 82 ). The above studies provide strong evidence for the antiviral efficacy of molnupiravir.…”

Section: Efficacy In Animal Modelsmentioning

confidence: 99%

Molnupiravir and Its Antiviral Activity Against COVID-19

et al. 2022

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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major worldwide public health threat and economic burden. The pandemic is still ongoing and the SARS-CoV-2 variants are still emerging constantly, resulting in an urgent demand for new drugs to treat this disease. Molnupiravir, a biological prodrug of NHC (β-D-N(4)-hydroxycytidine), is a novel nucleoside analogue with a broad-spectrum antiviral activity against SARS-CoV, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), influenza virus, respiratory syncytial virus (RSV), bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV) and Ebola virus (EBOV). Molnupiravir showed potent therapeutic and prophylactic activity against multiple coronaviruses including SARS-CoV-2, SARS-CoV, and MERS-CoV in animal models. In clinical trials, molnupiravir showed beneficial effects for mild to moderate COVID-19 patients with a favorable safety profile. The oral bioavailability and potent antiviral activity of molnupiravir highlight its potential utility as a therapeutic candidate against COVID-19. This review presents the research progress of molnupiravir starting with its discovery and synthesis, broad-spectrum antiviral effects, and antiviral mechanism. In addition, the preclinical studies, antiviral resistance, clinical trials, safety, and drug tolerability of molnupiravir are also summarized and discussed, aiming to expand our knowledge on molnupiravir and better deal with the COVID-19 epidemic.

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“…Patients with liver illnesses reportedly have higher GM-CSF levels, and may be crucial for both host defense and disease progression ( 68 ). GM-CSF is suggestive of pro-inflammatory polarization in HCV patients with cirrhosis ( 69 ). A decrease in GM-CSF reflects weakened proliferation and differentiation of the myeloid lineage during chronic infection, and here, with the HIV-infected group in the current investigation.…”

Section: Discussionmentioning

confidence: 99%

Plasma interleukin-7 correlation with human immunodeficiency virus RNA and CD4+ T cell counts, and interleukin-5 with circulating hepatitis B virus DNA may have implications in viral control

Vimali

Yong²,

Murugesan³

et al. 2022

Front. Med.

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Chronic viral infections represent a leading cause of global morbidity and mortality. Chronic HBV, HCV, and HIV infections result in cytokine perturbations that may hold key implications in understanding the complex disease mechanisms driving virus persistence and/or resolution. Here, we determined the levels of various plasma cytokines using a commercial Bio-Plex Luminex cytokine array in chronic HBV (n = 30), HCV (n = 15), and HIV (n = 40) infections and correlated with corresponding plasma viral loads (PVLs) and liver parameters. We observed differential perturbations in cytokine profiles among the study groups. The cytokines levels positively correlated with PVL and liver transaminases. The monocyte-derived cytokines viz., MIP-1β, IL-8, and TNF-α, and Th2 cytokines like IL-4, IL-5, and IL-13 showed a better correlation with liver enzymes as compared to their corresponding PVLs. Our investigation also identified two cytokines viz., IL-5 and IL-7 that inversely correlated with HBV DNA and HIV PVLs, respectively. Regression analysis adjusted for age showed that every increase of IL-5 by one unit was associated with a reduction in HBV PVL by log10 0.4, whereas, every elevation by a unit of IL-7 was associated with decreased HIV PVL by log10 2.5. We also found that IL-7 levels correlated positively with absolute CD4+ T cell counts in HIV-infected patients. We concluded that plasma IL-5 and IL-7 may likely have a key role on viral control in HBV and HIV infections, respectively. A noteworthy increase in cytokines appears to bear protective and pathological significance, and indeed is reflective of the host’s versatile immune armory against viral persistence.

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Remodeling of immunological biomarkers in patients with chronic hepatitis C treated with direct-acting antiviral therapy

Cited by 8 publications

References 24 publications

The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C

The Effect of Treatment-Induced Viral Eradication on Cytokine and Growth Factor Expression in Chronic Hepatitis C

Molnupiravir and Its Antiviral Activity Against COVID-19

Plasma interleukin-7 correlation with human immunodeficiency virus RNA and CD4+ T cell counts, and interleukin-5 with circulating hepatitis B virus DNA may have implications in viral control

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