CD27(+)CD56Bright natural killer cells may be involved in spontaneous clearance of acute hepatitis C in HIV-positive patients.

Objective: The objective of this study was to analyse the potential role of CD27 in natural killer (NK) cell-mediated control of hepatitis C virus (HCV) infection in HIV-positive patients.

Design: Frequency of CD27-expressing CD56 NK cells was analysed in HIV mono-infected individuals and HIV-positive patients with acute or chronic hepatitis C. Anti-HCV activity of CD27(+) and CD27(-) NK cells was compared.

An effective interferon-gamma-mediated inhibition of hepatitis C virus replication by natural killer cells is associated with spontaneous clearance of acute hepatitis C in human immunodeficiency virus-positive patients.

Unlabelled: Hepatitis C virus (HCV) coinfection is an increasing health problem in human immunodeficiency virus-positive (HIV(+) ) individuals. However, a considerable proportion of HIV(+) patients manage to overcome acute hepatitis C (AHC) spontaneously. In the present study, we analyzed the role of natural killer (NK) cells in modulating the course of AHC in HIV(+) patients.

Influence of the CXCL1 rs4074 A allele on alcohol induced cirrhosis and HCC in patients of European descent.

Background And Aims: CXCL1 (CXC chemokine-ligand-1) is a ligand for CXC chemokine receptor 2 expressed on hepatic stellate cells (HSC). Thus, CXCL1 might contribute to HSC activation and fibrogenesis. In the present study, we investigated the influence of the CXCL1 rs4074 polymorphism on the occurrence of alcohol induced liver cirrhosis and hepatocellular carcinoma (HCC).

Impaired CD4⁺ T cell stimulation of NK cell anti-fibrotic activity may contribute to accelerated liver fibrosis progression in HIV/HCV patients.

Background & Aims: HIV/HCV co-infection is characterized by a faster progression to liver fibrosis compared to HCV mono-infection. Epidemiologic studies found an association between low CD4(+) T cell counts and advanced stages of liver fibrosis. However, the mechanisms underlying this association remain unclear.

The CXCR3(+)CD56Bright phenotype characterizes a distinct NK cell subset with anti-fibrotic potential that shows dys-regulated activity in hepatitis C.

Background: In mouse models, natural killer (NK) cells have been shown to exert anti-fibrotic activity via killing of activated hepatic stellate cells (HSC). Chemokines and chemokine receptors critically modulate hepatic recruitment of NK cells. In hepatitis C, the chemokine receptor CXCR3 and its ligands have been shown to be associated with stage of fibrosis suggesting a role of these chemokines in HCV associated liver damage by yet incompletely understood mechanisms.

Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis.

Unlabelled: Natural killer (NK) cells play a role in the early control and natural course of hepatitis C virus (HCV) infection. NK cell function is regulated by a multitude of receptors, including activating NKp46 receptor. However, reports on NKp46 in hepatitis C are controversial.

NK cells from HCV-infected patients effectively induce apoptosis of activated primary human hepatic stellate cells in a TRAIL-, FasL- and NKG2D-dependent manner.

In mouse models it has been shown that natural killer (NK) cells can attenuate liver fibrosis via killing of activated hepatic stellate cells (HSCs) in a NKG2D- and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-dependent manner. However, only little data exist regarding interactions of human NK cells with HSCs and their potential role in hepatitis C virus (HCV)-associated fibrogenesis. Therefore, purified NK cells from untreated HCV RNA(+) patients (n=33), interferon-α (IFN-α)-treated patients (n=17) and healthy controls (n=18) were coincubated with activated primary HSCs, and were tested for degranulation (CD107a expression) and secretion of IFN-γ and TNF-α, respectively.

TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients.

Background: Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (DR4) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed DR4 mutations C626G (rs20575) and A683C (rs20576) in HCV-infected patients with and without HCC.

Methods: Frequencies of DR4 gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively.