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.

Visual outcomes of combined use of implantable collamer lens implantation and laser corneal visual correction for myopia over -18.00 diopters.

Purpose: To explore visual outcomes in patients with extreme myopia receiving an implantable collamer lens (ICL) at -18.00 diopters (D), with central port, followed by bioptics by laser vision correction (laser in situ keratomileusis [LASIK] or photorefractive keratectomy [PRK]) to address residual myopia or myopic astigmatism.

Setting: Clínica Baviera (Aier Eye Hospital Group), Bilbao, Spain.

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]).

Bictegravir/Emtricitabine/Tenofovir Alafenamide in a Multicentre Cohort: Real-Life Experience From Spain.

Background: The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce.

Objective: To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort.

Methods: This observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022.

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.

Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment.

Background: Antiviral treatment of patients with chronic hepatitis B (CHB) in the grey zone of treatment comands risk management in order to optimize the health outcome. In this sense, the identification of HBV mutants related with an increased risk of hepatocellular carcinoma (HCC) could be useful to identify subpopulations with potential indication of antiviral treatment.

Aim: To analyze the prevalence/persistence of hepatitis B virus (HBV) preS and basal core promoter (BCP)/precore/core variants associated to HCC development in CHB patients in the grey zone.

The linguistic signature of hallucinated voice talk in schizophrenia.

Very few studies have investigated the formal linguistic aspects of auditory verbal hallucinations (AVHs), though speech is a defining aspect of AVHs. Hallucinated speech heard by 19 patients with schizophrenia and highly frequent voices was obtained online, as and when they spoke, and annotated for pre-selected linguistic variables. Results showed that, consistently across the sample, (i) the grammatical first Person was significantly less represented than both second and third person, and often absent altogether; (ii) overwhelmingly, isolated clauses with no grammatical connectivity (parataxis) were produced, as compared with subordinations, coordinations, and adjunctions; (iii) in all participants except one, virtually no noun phrases (NPs) were anaphoric ones, back-referring to previous NPs, illustrating again a lack of connectivity across utterances.

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.

Specific CD8(+) T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis.

Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8(+) T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8(+) T cell response.

[Severe acute hepatitis by delta virus superinfection: diagnostic significance of molecular biology.].

HDV infection may occur within a primary HBV infection (co-infection) or by sub sequent acquisition ofthe virus in patients with chronic hepatitis B (superinfection). Acute HDV infection is rarely diagnosed. Since cero conversion usually takes place about six weeks after viral infection, early diagnosis requires the use of direct diagnostic techniques, such as antigen HD V (HDAg) detection, or genomic amplification by means of molecular biology methods (RT-PCR).

Validation of the Spanish version of the Clinical Assessment for Negative Symptoms (CAINS).

Negative symptoms are a core feature of schizophrenia and their reliable and valid assessment is a prerequisite for developing effective therapeutic interventions. This study examined the psychometric properties and validity of the Spanish version of a new rating instrument, the Clinical Assessment Interview for Negative Symptoms (CAINS). Outpatients and inpatients (N=100) with DSM-IV schizophrenia were administered the translated CAINS, the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale for Schizophrenia (CDSS).

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.

Undetectable HCV-RNA at treatment-week 8 results in high-sustained virological response in HCV G1 treatment-experienced patients with advanced liver disease: the International Italian/Spanish Boceprevir/Peginterferon/Ribavirin Name Patients Program.

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study.

Safety and efficacy of triple therapy with peginterferon, ribavirin and boceprevir within an early access programme in Spanish patients with hepatitis C genotype 1 with severe fibrosis: SVRw12 analysis.

Background & Aims: The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection.

Methods: Prospective, multicentre, national registry that includes naïve and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics.

Results: Most of the patients (68.

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.

Persistent hepatitis C virus (HCV) infection impairs HCV-specific cytotoxic T cell reactivity through Mcl-1/Bim imbalance due to CD127 down-regulation.

In persistent hepatitis C virus (HCV) infection, HCV-specific cytotoxic T lymphocyte (CTL) reactivity is impaired and this affects HCV control. Interleukin-7 receptor (CD127) expression on these cells could regulate CTL reactivity through Mcl-1/Bim balance modulation. Bim is a pro-apoptotic molecule blocked by the action of Mcl-1.