Lack of TGF-β production by hepatitis C virus-specific T cells during HCV acute phase is associated with HCV clearance in HIV coinfection

Harfouch, Sawsan; Guiguet, Marguerite; Valantin, Marc‐Antoine; Samri, Assia; Ouazene, Zineb; Slama, Laurence; Dominguez, Stéphanie; Simon, Anne; Théodorou, Ioannis; Thibault, Vincent; Autran, Brigitte

doi:10.1016/j.jhep.2012.01.021

Cited by 8 publications

(3 citation statements)

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“…In this context, TGF-b is a cytokine with multiple functions that has been associated with the development of hepatic fibrosis [20,21]. However, the role of TGF-b on the outcome of treatment against HCV is unclear and data are scarce and contradictory [22][23][24][25][26][27]. In this regard, high TGF-b levels have been described to diminish response to dual therapy in this population [22].…”

Section: Discussionmentioning

confidence: 99%

Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection

Neukam

Caruz

Rivero‐Juárez

et al. 2013

Aids

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Section: Discussionmentioning

confidence: 99%

Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection

Neukam

Caruz

Rivero‐Juárez

et al. 2013

Aids

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“…Suppression of peripheral HCV‐specific IFNγ was predominantly mediated by TGFβ rather than IL‐10. The presence of HCV‐specific CD4 and CD8 T cells producing TGFβ was recently confirmed in peripheral blood mononuclear cells (PBMCs) in acute HCV infection 37…”

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confidence: 93%

Hepatitis c virus-specific t-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis

Vriend

Nasser

et al. 2012

Hepatology

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Background/Aims Hepatitis C virus (HCV)-specific immune effector responses can cause liver damage in chronic infection. Hepatic stellate cells (HSC) are main effectors of liver fibrosis. We previously identified TGFβ, produced by HCV-specific CD8+ T cells, as key regulatory cytokine modulating HCV-specific effector T cells. Here we studied TGFβ as well as other factors produced by HCV-specific intrahepatic lymphocytes (IHL) and peripheral blood cells in hepatic inflammation and fibrogenesis. Methods Cross-sectional study of 2 well-defined groups of HCV-infected subjects with slow (≤0.1 Metavir units/year, n=13) or rapid (n=6) liver fibrosis progression. HCV-specific T cell responses were studied using IFNγ-ELISpot ±mAbs blocking regulatory cytokines, along with multiplex, ELISA and multi-parameter FACS. Effects of IHL stimulated with HCV-core peptides on HSC expression of pro-fibrotic and fibrolytic genes were determined. Results Blocking regulatory cytokines significantly raised detection of HCV-specific effector (IFNγ) responses only in slow fibrosis progressors, both in the periphery (p=0.003) and liver (p=0.01). Regulatory cytokine blockade revealed HCV-specific IFNγ responses strongly correlated with HCV-specific TGFβ, measured before blockade (R=0.84, p=0.0003), with only trend to correlation with HCV-specific IL-10. HCV-specific TGFβ was produced by CD8 and CD4 T cells. HCV-specific TGFβ, not IL-10, inversely correlated with liver inflammation (R=-0.63, p=0.008) and, unexpectedly, fibrosis (R=-0.46, p=0.05). In addition, supernatants from HCV-stimulated IHL of slow progressors specifically increased fibrolytic gene expression in HSC and treatment with anti-TGFβ mAb abrogated such expression. Conclusion Although TGFβ is considered a major profibrogenic cytokine, local production of TGFβ by HCV-specific T cells appeared to have a protective role in HCV-infected liver, together with other T-cell derived factors, ameliorating HCV liver disease progression.

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“…The probability of SC for the patient was not estimated in our study, but previous works indicated that approximately 15%–20% of HIV-HCV coinfected individuals clear infection spontaneously [13, 30, 31]. However, these probabilities might constitute underestimates of the overall chance of SC because patients generally receive therapy while they might potentially still have a chance to spontaneously clear the HCV infection.…”

Section: Discussionmentioning

confidence: 82%

Estimating the Time to Diagnosis and the Chance of Spontaneous Clearance During Acute Hepatitis C in Human Immunodeficiency Virus-Infected Individuals

Ragonnet

Deuffic-Burban

Boesecke

et al. 2017

Open Forum Infectious Diseases

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Background.Hepatitis C virus (HCV) infection is often asymptomatic, and the date of infection is almost impossible to determine. Furthermore, spontaneous clearance (SC) may occur, but little is known about its time of occurrence.Methods.Data on human immunodeficiency virus (HIV)-HCV coinfected individuals were used to inform a stochastic simulation model of HCV viral load kinetics, alanine aminotransferase (ALT), and HCV antibodies during acute hepatitis C. The dates of diagnosis and potential SC were estimated through a Bayesian approach. Hepatitis C virus diagnosis was assumed to be based on an elevated ALT level detected during a control visit for HIV-infected individuals, which occurred every 3 months (scenario A) or every 6 months (scenario B).Results.We found that HCV diagnosis occurred after a median of 115 days and 170 days of infection in scenarios A and B, respectively. Among spontaneous clearers, SC occurred after a median time of 184 days after infection. Seven percent (scenario B) to 10% (scenario A) of SCs appeared more than 6 months after diagnosis, and 3% (both scenarios) of SCs appeared more than 1 year after diagnosis.Conclusions.Acute hepatitis C diagnosis occurs late in HIV-HCV coinfected individuals. Screening for HCV in HIV-infected individuals should be performed frequently to reduce delays. Our findings about late occurrence of SC support “wait and see” strategies for treatment initiation from an individual basis. However, early treatment initiation may reduce HCV transmission.

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Lack of TGF-β production by hepatitis C virus-specific T cells during HCV acute phase is associated with HCV clearance in HIV coinfection

Cited by 8 publications

References 53 publications

Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection

Variations at multiple genes improve interleukin 28B genotype predictive capacity for response to therapy against hepatitis C infection

Hepatitis c virus-specific t-cell-derived transforming growth factor beta is associated with slow hepatic fibrogenesis

Estimating the Time to Diagnosis and the Chance of Spontaneous Clearance During Acute Hepatitis C in Human Immunodeficiency Virus-Infected Individuals

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