HBsAg level defines different clinical phenotypes of HBeAg(-) chronic HBV infection related to HBV polymerase-specific CD8 cell response quality.

Background: HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8 T-cell response.

Aims: To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8 T-cell response.

Methods: We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8 cell effector function were correlated with HBsAg level.

IL-15 boosts activated HBV core-specific CD8 progenitor cells via metabolic rebalancing in persistent HBV infection.

A rebalance between energy supply and demand in HBV-specific-CD8 activated progenitor (AP) cells could restore the functionality of proliferative progeny (PP) in e-antigen(Ag)-negative chronic hepatitis B (CHBe(-)). We observed that quiescent progenitor (QP [TCF1/FSC]) HBVcore-specific-CD8 cells displayed a memory-like phenotype. Following Ag-encounter, the generated AP [TCF1/FSC] subset maintained the PD1/CD127 phenotype and gave rise to proliferative progeny (PP [ TCF1/FSC]).

Model to predict on-treatment restoration of functional HBV-specific CD8 cell response foresees off-treatment HBV control in eAg-negative chronic hepatitis B.

Background: Hepatitis B virus (HBV)-specific CD8 cell response restoration during nucleos(t)ide analogue (NUC) treatment could lead to off-treatment HBV control in e-antigen-negative chronic hepatitis B (CHBe(-)).

Aim: To predict this response with variables involved in T-cell exhaustion for use as a treatment stopping tool.

Methods: In NUC-treated CHBe(-) patients, we considered a functional response in cases with HBV-specific CD8 cells against core and polymerase HBV epitopes able to proliferate and secrete type I cytokines after antigen encounter.

Anti-PD-1/PD-L1 Based Combination Immunotherapy to Boost Antigen-Specific CD8 T Cell Response in Hepatocellular Carcinoma.

Thirty to fifty percent of hepatocellular carcinomas (HCC) display an immune class genetic signature. In this type of tumor, HCC-specific CD8 T cells carry out a key role in HCC control. Those potential reactive HCC-specific CD8 T cells recognize either HCC immunogenic neoantigens or aberrantly expressed host's antigens, but they become progressively exhausted or deleted.

Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8 T Cell Response during Chronic Hepatitis C.

Hepatitis C virus (HCV)-specific CD8 T cell response is essential in natural HCV infection control, but it becomes exhausted during persistent infection. Nowadays, chronic HCV infection can be resolved by direct acting anti-viral treatment, but there are still some non-responders that could benefit from CD8 T cell response restoration. To become fully reactive, T cell needs the complete release of T cell receptor (TCR) signalling but, during exhaustion this is blocked by the PD-1 effect on CD28 triggering.

Tumor necrosis family receptor superfamily member 9/tumor necrosis factor receptor-associated factor 1 pathway on hepatitis C viral persistence and natural history.

Hepatitis C virus (HCV) infection is an excellent immunological model for understanding the mechanisms developed by non-cytopathic viruses and tumors to evade the adaptative immune response. The antigen-specific cytotoxic T cell response is essential for keeping HCV under control, but during persistent infection, these cells become exhausted or even deleted. The exhaustion process is progressive and depends on the infection duration and level of antigenemia.

Is it possible to stop nucleos(t)ide analogue treatment in chronic hepatitis B patients?

Chronic hepatitis B (CHB) remains a challenging global health problem, with nearly one million related deaths per year. Nucleos(t)ide analogue (NA) treatment suppresses viral replication but does not provide complete cure of the hepatitis B virus (HBV) infection. The accepted endpoint for therapy is the loss of hepatitis B surface antigen (HBsAg), but this is hardly ever achieved.

According to Hepatitis C Virus (HCV) Infection Stage, Interleukin-7 Plus 4-1BB Triggering Alone or Combined with PD-1 Blockade Increases TRAF1 HCV-Specific CD8 Cell Reactivity.

Hepatitis C virus (HCV)-specific CD8 T cells suffer a progressive exhaustion during persistent infection (PI) with HCV. This process could involve the positive immune checkpoint 4-1BB/4-1BBL through the loss of its signal transducer, TRAF1. To address this issue, peripheral HCV-specific CD8 T cells (pentamer-positive [pentamer]/CD8 T cells) from patients with PI and resolved infection (RI) after treatment were studied.

Pancreatic pseudocyst drainage performed with a new prototype forward-viewing linear echoendoscope.

Interventional endoscopy is a field that continues to grow rapidly. A novel prototype forward-viewing echoendoscope (FV-EUS) has been recently developed in an attempt to overcome some of the limitations of conventional curved linear-array echoendoscopes (OV-EUS). We present a case of a successful endoscopic ultrasound-guided drainage of a pancreatic pseudocyst using a forward-viewing echoendoscope.

Hepatitis C virus-specific cytotoxic T cell response restoration after treatment-induced hepatitis C virus control.

Hepatitis C virus (HCV)-specific cytotoxic T cell (CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response (SVR) after anti-HCV is controversial.

Adaptive immune response during hepatitis C virus infection.

Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors.

HCV-specific CD8+ cell detection at week 12 of chronic hepatitis C treatment with PEG-interferon-α2b/ribavirin correlates with infection resolution.

Lower than 2-log viral-load (VL) decrease at week 12 (w12) of chronic hepatitis C (CHC) treatment with Peg-interferon/ribavirin has 100% negative predictive value (PV) of sustained virologic response (SVR), and this could be related with absence of HCV-specific cytotoxic T lymphocyte (CTL) response. In this study, percentage of cases with SVR, according to peripheral HCV-specific cytotoxic response at w12, was analysed (Group-1: detection(+), Group-2: detection(-)). SVR was higher in group-1 (93%) than in group-2 (47%) (p=0.

Bim-mediated apoptosis and PD-1/PD-L1 pathway impair reactivity of PD1(+)/CD127(-) HCV-specific CD8(+) cells targeting the virus in chronic hepatitis C virus infection.

PD-1 molecule promotes anergy and IL-7 receptor (CD127) induces an anti-apoptotic effect on T cells. Correlation between PD-1/CD127 phenotype and hepatitis C virus (HCV)-specific CD8(+) cell reactivity in resolved infection (RI) after treatment and persistent HCV-infection (PI) was analysed. Directly ex vivo, PD-1 and CD127 expression on HCV-specific CD8(+) cells displayed a positive and negative correlation, respectively with viraemia.

Costimulatory molecule programmed death-1 in the cytotoxic response during chronic hepatitis C.

Hepatitis C virus (HCV)-specific CD8(+) T cells play an important role in the resolution of HCV infection. Nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control.

The role of CCR5/CXCR3 expressing CD8+ cells in liver damage and viral control during persistent hepatitis C virus infection.

Background/aims: CXCR3 and CCR5 play a major role in recruiting cytotoxic T cells (Tc) and secreting secondary type 1 cytokines (Tc1) in the liver. HCV could impair their expression as a survival mechanism. The role of these chemokine receptors on CD8+ cells in chronic hepatitis C is analysed.