Immune Reconstitution After HCV Clearance With Direct Antiviral Agents

Werner, Jens; Adenugba, Akinbami; Protzer, Ulrike

doi:10.1097/tp.0000000000001606

Cited by 33 publications

(29 citation statements)

References 49 publications

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“…Virus-specific T cell responses are skewed in the chronic phase of HCV infection, due to viral escape and functional exhaustion of virus-specific CD4 + and CD8 + T cells ( 10 ). Consequently, remaining antigen-specific T cells show increased expression of inhibitory molecules such as programmed death-1 and 2B4 (CD244) ( 11 ). Accordingly, in this study, patients receiving DAA treatment were comprehensively monitored to identify immunologically related biomarkers from peripheral blood that accurately predicted early HCV RNA negativity.…”

Section: Introductionmentioning

confidence: 99%

Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers

et al. 2018

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Recent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus (HCV) infection. Regrettably, the high cost of DAA treatment is burdensome for healthcare systems and may be prohibitive for some patients who would otherwise benefit. Understanding how patient-related factors influence individual responses to DAA treatment may lead to more efficient prescribing. In this observational study, patients with chronic HCV infection were comprehensively monitored by flow cytometry to identify pretreatment immunological variables that predicted HCV RNA negativity within 4 weeks of commencing DAA treatment. Twenty-three patients [genotype 1a (n = 10), 1b (n = 9), and 3 (n = 4)] were treated with daclatasvir plus sofosbuvir (SOF) (n = 15), ledipasvir plus SOF (n = 4), or ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir (n = 4). DAA treatment most prominently altered the distribution of CD8+ memory T cell subsets. Knowing only pretreatment frequencies of CD3+ and naive CD8+ T cells allowed correct classification of 83% of patients as “fast” (HCV RNA-negative by 4 weeks) or “slow” responders. In a prospective cohort, these parameters correctly classified 90% of patients. Slow responders exhibited higher frequencies of CD3+ T cells, CD8+ TEM cells, and CD5high CD27− CD57+ CD8+ chronically activated T cells, which is attributed to bystander hyperactivation of virus-non-specific CD8+ T cells. Taken together, non-specific, systemic CD8+ T cell activation predicted a longer time to viral clearance. This discovery allows pretreatment identification of individuals who may not require a full 12-week course of DAA therapy; in turn, this could lead to individualized prescribing and more efficient resource allocation.

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Section: Introductionmentioning

confidence: 99%

Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers

et al. 2018

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“…Another particular issue that came to light with the first "warning report" concerns the possibility of HCV clearance from the liver, and the consequent impairment of the local immunological microenvironment, having an impact on HCC biology [ Table 3]. Chronic stimulation of antigens against HCV infection contributes to virus-specific CD8+ T-cell exhaustion, continuative activation of host-mediated liver inflammation (driven partly by endogenous IFNs), and altered innate immune cell populations [67,68] . IFN can modulate both innate and adaptive immune system.…”

Section: Possible Pathogenic Mechanismsmentioning

confidence: 99%

Direct-acting antivirals and hepatocellular carcinoma occurrence and recurrence in hepatitis C virus-related liver cirrhosis: fact or finction

Zanetto¹,

Shalaby²,

Ferrarese³

et al. 2018

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Since the widespread adoption of new direct-acting antiviral agents (DAAs), the approach to hepatitis C virus (HCV) infection has changed profoundly as almost all patients can be cured regardless of the stage of their liver disease. On the other hand, there are a few conflicting reports on the risk of hepatocellular carcinoma (HCC) occurring and recurring in patients given DAA-based therapy. The present review focuses on the latest and most relevant literature providing evidence on the occurrence and recurrence of HCC after HCV antiviral treatment with the new DAAs. Retaining the distinction between HCC occurrence and recurrence, we also discuss its patterns of presentation and speculate on the possible pathogenic mechanisms. We offer our personal viewpoints on this important issue, which has kept clinicians second-guessing in real-world clinical practice, when dealing with HCV eradication in the setting of advanced liver disease in this interferon-free era.

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“…Treatment with DAA can eradicate serum HCV RNA, however, viral mutation was reported after DAA treatment . Moreover, treatment is costly and reinfection, reactivation of other viruses, and liver failure may occur after achievement of sustained virological response (SVR) …”

Section: Introductionmentioning

confidence: 99%

Rapid hepatitis C virus clearance by antivirals correlates with immune status of infected patients

Sasaki

Meyer

Moriyama

et al. 2018

Journal of Medical Virology

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Altered immune parameters associated with hepatitis C virus (HCV) genotype 1b infection and their correlation with virus eradication in direct-acting antivirals (DAA)-treated patients were examined. Thirty-one HCV-infected patients were treated with DAAs for 12 weeks. Pre-DAA-treatment and post-DAA-treatment sera were analyzed for cytokines/chemokines using MILLIPLEX MAP. Serum complement level and antibody neutralization activity were measured separately. Sera from 11 spontaneously cleared HCV subjects were included for comparison. Rapid virological responders (RVR) or end-of-treatment responders (EOTR) were defined as patients with HCV RNA negative at week 4 or positive at week 4 and negative at week 12, respectively. HCV RNA eradication and a decrease in liver fibrosis-related cytokines after treatment were observed when compared with pretreatment sera from RVR and EOTR. In pretreatment sera, interferons and T-helper 1 or 2 cell-associated cytokines/chemokines were significantly higher among RVR as compared with EOTR. Furthermore, serum complement and virus neutralizing antibody levels were higher in pretreatment RVR sera. Eradication of HCV RNA by DAA decreased liver fibrosis-related cytokines. Pretreatment sera from RVR displayed an enhanced cytokine/chemokine, complement and virus neutralizing antibody response as compared with EOTR sera. Our results suggested that enhanced host immune status may play an additive role on HCV RNA clearance by DAA.

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Immune Reconstitution After HCV Clearance With Direct Antiviral Agents

Cited by 33 publications

References 49 publications

Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers

Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers

Direct-acting antivirals and hepatocellular carcinoma occurrence and recurrence in hepatitis C virus-related liver cirrhosis: fact or finction

Rapid hepatitis C virus clearance by antivirals correlates with immune status of infected patients

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