Acute hepatitis C virus infection

Around 25% of people infected with hepatitis C virus (HCV) are able to clear the infection spontaneously, while the majority become chronically infected, with a subsequent risk for the individual patient of progressive inflammatory liver disease, cirrhosis, hepatocellular carcinoma and liver-related death (Figure 1). Much is known about the epidemiology, pathogenesis, diagnosis and management of chronic HCV infection. In comparison, knowledge about acute HCV infection is patchy. In this article, we will highlight concerns relating to acute HCV infection and suggest that public health bodies responsible for managing the HCV epidemic should redirect at least some of their resources to dealing with these issues.

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PD-1 Expression in Acute Hepatitis C Virus (HCV) Infection Is Associated with HCV-Specific CD8 Exhaustion

Journal of Virology ◽

10.1128/jvi.01177-06 ◽

2006 ◽

Vol 80 (22) ◽

pp. 11398-11403 ◽

Cited By ~ 399

Author(s):

Simona Urbani ◽

Barbara Amadei ◽

Daniela Tola ◽

Marco Massari ◽

Simona Schivazappa ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Cell Function ◽

Hcv Infection ◽

Acute Hepatitis C ◽

Inhibitory Receptor ◽

Cd8 Cells ◽

Acute Hcv ◽

Cd8 Cell ◽

Acute Hcv Infection

ABSTRACT Hepatitis C virus (HCV)-specific CD8 cell exhaustion may represent a mechanism of HCV persistence. The inhibitory receptor PD-1 has been reported to be up-regulated in exhausted CD8 cells. Therefore, we studied PD-1 expression longitudinally during acute HCV infection. Most HCV-specific CD8 cells expressed PD-1 at the time of acute illness, irrespective of the final outcome. PD-1 expression declined with the acquisition of a memory phenotype and recovery of an efficient CD8 cell function in resolving HCV infections, whereas high levels were maintained when HCV persisted and HCV-specific CD8 cells remained dysfunctional. Blocking PD-1/PDL-1 interaction with an anti-PDL-1 antibody improved the capacity of expansion of virus-specific CD8 cells.

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Initial Presentation of Acute Hepatitis C Virus (HCV) Infection among HIV–Negative and HIV‐Positive Individuals—Experience from 2 Large German Networks on the Study of Acute HCV Infection

Clinical Infectious Diseases ◽

10.1086/600058 ◽

2009 ◽

Vol 49 (2) ◽

pp. 317-319 ◽

Cited By ~ 38

Author(s):

Martin Vogel ◽

Katja Deterding ◽

Johannes Wiegand ◽

Norbert H. Grüner ◽

Axel Baumgarten ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Acute Hepatitis ◽

Hcv Infection ◽

Initial Presentation ◽

Hiv Positive ◽

Acute Hepatitis C ◽

Acute Hcv ◽

Acute Hcv Infection ◽

Hiv Negative

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Detection of host immune responses in acute phase sera of spontaneous resolution versus persistent hepatitis C virus infection

Journal of General Virology ◽

10.1099/vir.0.041277-0 ◽

2012 ◽

Vol 93 (8) ◽

pp. 1673-1679 ◽

Cited By ~ 5

Author(s):

Suganya Selvarajah ◽

Sheila Keating ◽

John Heitman ◽

Kai Lu ◽

Graham Simmons ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Immune Responses ◽

Serum Levels ◽

Hcv Infection ◽

Serum Samples ◽

Necrosis Factor Alpha ◽

Acute Hcv ◽

Chronic Hcv ◽

Acute Hcv Infection

Prior to the identification of hepatitis C virus (HCV), transfusion-transmission was common. Viral transmission in subjects with a known date of infection allows the study of the immune responses to acute HCV infection. We analysed 39 soluble immune factors in serum samples from subjects with transfusion-transmitted HCV. Dynamic expression kinetics of interferon gamma-induced protein 10 (IP-10), tumour necrosis factor-alpha and interleukin (IL)-10 were observed during acute HCV infection. Serum IP-10 was the only analyte that was significantly elevated in HCV resolvers compared with uninfected controls. In individuals who progressed to chronic HCV elevated levels of IP-10 and IL-10 coincided with first significant alanine aminotransferase elevation and remained elevated during the first year of acute HCV infection. In addition to monitoring lack of reduction in viral load, serum levels of IP-10 and IL-10 expression during acute HCV infection may be useful biomarkers to predict the progress to chronic HCV.

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Phenotypic and Functional Changes of Cytotoxic CD56pos Natural T Cells Determine Outcome of Acute Hepatitis C Virus Infection

Journal of Virology ◽

10.1128/jvi.00834-07 ◽

2007 ◽

Vol 81 (17) ◽

pp. 9292-9298 ◽

Cited By ~ 43

Author(s):

Lucy Golden-Mason ◽

Nicole Castelblanco ◽

Cliona O'Farrelly ◽

Hugo R. Rosen

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Spontaneous Recovery ◽

Acute Infection ◽

Hcv Infection ◽

Receptor Expression ◽

Acute Hepatitis C ◽

Functional Changes ◽

Acute Hcv ◽

Acute Hcv Infection

ABSTRACT Innate CD56pos natural killer (NK) and natural T (NT) cells comprise important hepatic antiviral effector lymphocytes whose activity is fine-tuned through surface NK receptors (NKRs). Dysregulation of NKRs in patients with long-standing hepatitis C virus (HCV) infection has been shown, but little is known regarding NKRs in acute infection. Treatment-naïve patients with acute HCV (n = 22), including 10 with spontaneous recovery, were prospectively studied. CD56pos NT levels were reduced early in acute HCV infection and did not fluctuate over time. In resolving HCV infection, NT cells with a more activated phenotype (lower CD158A and higher natural cytotoxicity receptor expression) at baseline predated spontaneous recovery. Moreover, NKG2A expression on CD56+ NT cells correlated directly with circulating HCV RNA levels. Deficient interleukin-13 (IL-13) production by NT cells and reduced IL-2-activated killing (LAK) at baseline were associated with the ultimate development of persistence. These results indicate a previously unappreciated role for NT cells in acute HCV infection and identify a potential target for pharmacologic manipulation.

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Early Interferon Therapy for Hepatitis C Virus Infection Rescues Polyfunctional, Long-Lived CD8+ Memory T Cells

Journal of Virology ◽

10.1128/jvi.01083-08 ◽

2008 ◽

Vol 82 (20) ◽

pp. 10017-10031 ◽

Cited By ~ 105

Author(s):

Gamal Badr ◽

Nathalie Bédard ◽

Mohamed S. Abdel-Hakeem ◽

Lydie Trautmann ◽

Bernard Willems ◽

...

Keyword(s):

T Cells ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Therapeutic Intervention ◽

Memory T Cells ◽

Hcv Infection ◽

Effector Memory ◽

Acute Hepatitis C ◽

Acute Hcv ◽

Acute Hcv Infection

ABSTRACT The majority of acute hepatitis C virus (HCV) infections progress to chronicity and progressive liver damage. Alpha interferon (IFN-α) antiviral therapy achieves the highest rate of success when IFN-α is administered early during the acute phase, but the underlying mechanisms are unknown. We used a panel of major histocompatibility complex class I tetramers to monitor the phenotypic and functional signatures of HCV-specific T cells during acute HCV infection with different infection outcomes and during early IFN therapy. We demonstrate that spontaneous resolution correlates with the early development of polyfunctional (IFN-γ- and IL-2-producing and CD107a+) virus-specific CD8+ T cells. These polyfunctional T cells are distinguished by the expression of CD127 and Bcl-2 and represent a transitional memory T-cell subset that exhibits the phenotypic and functional signatures of both central and effector memory T cells. In contrast, HCV-specific CD8+ T cells in acute infections evolving to chronicity expressed low levels of CD127 and Bcl-2, exhibited diminished proliferation and cytokine production, and eventually disappeared from the periphery. Early therapeutic intervention with pegylated IFN-α rescued polyfunctional memory T cells expressing high levels of CD127 and Bcl-2. These cells were detectable for up to 1 year following discontinuation of therapy. Our results suggest that the polyfunctionality of HCV-specific T cells can be predictive of the outcome of acute HCV infection and that early therapeutic intervention can reconstitute the pool of long-lived polyfunctional memory T cells.

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Treatment of acute hepatitis C infection with interferon-alfa 2b monotherapy prevents development of chronic HCV infection

Gastroenterology ◽

10.1016/s0016-5085(01)82820-1 ◽

2001 ◽

Vol 120 (5) ◽

pp. A567-A567 ◽

Cited By ~ 1

Author(s):

E JAECKEL ◽

M CORNBERG ◽

T SANTANTONIO ◽

J MAYER ◽

H WEDEMEYER ◽

...

Keyword(s):

Hepatitis C ◽

Acute Hepatitis ◽

Interferon Alfa ◽

Hcv Infection ◽

Acute Hepatitis C ◽

Hepatitis C Infection ◽

Chronic Hcv Infection ◽

Chronic Hcv

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Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus

Journal of Experimental Medicine ◽

10.1084/jem.191.9.1499 ◽

2000 ◽

Vol 191 (9) ◽

pp. 1499-1512 ◽

Cited By ~ 937

Author(s):

Franziska Lechner ◽

David K.H. Wong ◽

P. Rod Dunbar ◽

Roger Chapman ◽

Raymond T. Chung ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Acute Infection ◽

Hcv Infection ◽

Ctl Response ◽

Acute Hcv ◽

Ifn Γ ◽

Acute Hcv Infection

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-γ, a “stunned” phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection.

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