Natural History of Hepatic and Extrahepatic Hepatitis C Virus Diseases and Impact of Interferon-Free HCV Therapy

Negro, Francesco

doi:10.1101/cshperspect.a036921

Cited by 18 publications

(11 citation statements)

References 154 publications

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“…The fact that those T cells remain dysfunctional after HCV clearance might have serious clinical implications. Additional immunological therapy may reduce the risk of developing HCC and other extrahepatic manifestations after DAA regimen [ 54 ]. Unfortunately, patients who have overcome the infection and cleared the virus are not protected against reinfection [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

et al. 2021

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Background & aims HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV. Methods We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays. Results We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies. Conclusions Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA’s therapies.

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Section: Discussionmentioning

confidence: 99%

Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

et al. 2021

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“…Autoantibodies are present in a majority of HCV-infected patients, are a result of B cell dysregulation, and might contribute to extrahepatic manifestations of HCV infection such as mixed cryoglobulinemia. The autoantibody most frequently detected in patients with HCV infection is the anti-immunoglobulin autoantibody rheumatoid factor (RF) that is detectable in approximately 50% of patients with chronic HCV infection and contributes to the production of cryoglobulin [10,11]. Only a small fraction of HCV-specific antibodies have the capability to neutralize viral particles in vitro.…”

Section: Antibody Responsementioning

confidence: 99%

Adaptive Immune Response against Hepatitis C Virus

Kemming

Thimme

2020

IJMS

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A functional adaptive immune response is the major determinant for clearance of hepatitis C virus (HCV) infection. However, in the majority of patients, this response fails and persistent infection evolves. Here, we dissect the HCV-specific key players of adaptive immunity, namely B cells and T cells, and describe factors that affect infection outcome. Once chronic infection is established, continuous exposure to HCV antigens affects functionality, phenotype, transcriptional program, metabolism, and the epigenetics of the adaptive immune cells. In addition, viral escape mutations contribute to the failure of adaptive antiviral immunity. Direct-acting antivirals (DAA) can mediate HCV clearance in almost all patients with chronic HCV infection, however, defects in adaptive immune cell populations remain, only limited functional memory is obtained and reinfection of cured individuals is possible. Thus, to avoid potential reinfection and achieve global elimination of HCV infections, a prophylactic vaccine is needed. Recent vaccine trials could induce HCV-specific immunity but failed to protect from persistent infection. Thus, lessons from natural protection from persistent infection, DAA-mediated cure, and non-protective vaccination trials might lead the way to successful vaccination strategies in the future.

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“…HCV RNA levels rise rapidly during acute infection but it generally takes 4-12 wk for the elevation of alanine aminotransferase (ALT) (indicative of hepatic injury) with an associated increase of serum bilirubin[ 13 ]. HCV itself is not cytolytic, but it generates potent innate and adaptive immune responses with cytotoxic cytokines production and hepatic injury[ 14 ]. Acute liver failure due to HCV is rare, but its incidence increases especially in patients with pre-existing chronic liver diseases[ 12 ].…”

Section: Natural History Of Hcv Infectionmentioning

confidence: 99%

Risk of hepatocellular carcinoma after hepatitis C virus cure

Luna-Cuadros¹,

Chen²,

Hanif³

et al. 2022

WJG

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Hepatitis C virus (HCV) is a significant cause of hepatocellular carcinoma (HCC). The direct-acting antivirals marked a new era of HCV therapy and are associated with greater than 95% cure rate. Successful treatment of chronic hepatitis C greatly reduces the risk of HCC. A proportion of patients, especially those with pre-existing cirrhosis, remain at risk for HCC despite sustained virologic response (SVR). Diabetes mellitus, hepatic steatosis, alcohol consumption and lack of fibrosis regression are associated with risks of HCC after HCV cure. Noninvasive modalities such as aspartate aminotransferase to platelet ratio index and fibrosis-4 index and transient elastography have been used to monitor hepatic fibrosis. More recently, various fibrosis scores have been combined with clinical parameters and other novel biomarkers to predict risks of HCC for patients who achieved SVR. These models still need to be validated and standardized prior to applying to routine clinical care.

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Natural History of Hepatic and Extrahepatic Hepatitis C Virus Diseases and Impact of Interferon-Free HCV Therapy

Cited by 18 publications

References 154 publications

Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy

Adaptive Immune Response against Hepatitis C Virus

Risk of hepatocellular carcinoma after hepatitis C virus cure

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