Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges

AbstractChronic hepatitis B virus (HBV) infection due to mother-to-child transmission (MTCT) during perinatal period remains an important global health problem. Despite standard passive–active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in neonates, up to 9% of newborns still acquire HBV infection, especially these from hepatitis B e antigen (HBeAg) positive mothers. Management of HBV infection in pregnancy still need to draw careful attention because of some controversial aspects, including the failure of passive-active immunoprophylaxis in a fraction of newborns, the effect and necessity of periodical hepatitis B immunoglobulin (HBIG) injection to the mothers, the safety of antiviral prophylaxis with nucleoside/nucleotide analogs, the benefit of different delivery ways, and the safety of breastfeeding. In this review, we highlight these unsettled issues of preventive strategies in perinatal period, and we further aim to provide an optimal approach to the management of preventing MTCT of HBV infection

Identification and Validation of an Immune-Related eRNA Prognostic Signature for Hepatocellular Carcinoma

BackgroundEnhancer RNAs (eRNAs) are intergenic long non-coding RNAs (lncRNAs) that participate in the progression of malignancies by targeting tumor-related genes and immune checkpoints. However, the potential role of eRNAs in hepatocellular carcinoma (HCC) is unclear. In this study, we aimed to construct an immune-related eRNA prognostic model that could be used to prospectively assess the prognosis of patients with HCC.MethodsGene expression profiles of patients with HCC were downloaded from The Cancer Genome Atlas (TCGA). The eRNAs co-expressed from immune genes were identified as immune-related eRNAs. Cox regression analyses were applied in a training cohort to construct an immune-related eRNA signature (IReRS), that was subsequently used to analyze a testing cohort and combination of the two cohorts. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to validate the predictive effect in the three cohorts. Gene Set Enrishment Analysis (GSEA) computation was used to identify an IReRS-related signaling pathway. A web-based cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) computation was used to evaluate the relationship between the IReRS and infiltrating immune cells.ResultsA total of sixty-four immune-related eRNAs (IReRNAs) was identified in HCC, and 14 IReRNAs were associated with overall survival (OS). Five IReRNAs were used for constructing an immune-related eRNA signature (IReRS), which was shown to correlate with poor survival and to be an independent prognostic biomarker for HCC. The GSEA results showed that the IReRS was correlated to cancer-related and immune-related pathways. Moreover, we found that IReRS was correlated to infiltrating immune cells, including CD8+ T cells and M0 macrophages. Finally, differential expressions of the five risk IReRNAs in tumor tissues vs. adjacent normal tissues and their prognostic values were verified, in which the AL445524.1 may function as an oncogene that affects prognosis partly by regulating CD4-CLTA4 related genes.ConclusionOur results suggest that the IReRS could serve as a biomarker for predicting prognosis in patients with HCC. Additionally, it may be correlated to the tumor immune microenvironment and could also be used as a biomarker in immunotherapy for HCC

An M0 macrophage-related prognostic model for hepatocellular carcinoma

Abstract Background The role of M0 macrophages and their related genes in the prognosis of hepatocellular carcinoma (HCC) remains poorly characterized. Methods Multidimensional bioinformatic methods were used to construct a risk score model using M0 macrophage-related genes (M0RGs). Results Infiltration of M0 macrophages was significantly higher in HCC tissues than in normal liver tissues (P = 2.299e-07). Further analysis revealed 35 M0RGs that were associated with HCC prognosis; two M0RGs (OLA1 and ATIC) were constructed and validated as a prognostic signature for overall survival of patients with HCC. Survival analysis revealed the positive relationship between the M0RG signature and unfavorable prognosis. Correlation analysis showed that this risk model had positive associations with clinicopathological characteristics, somatic gene mutations, immune cell infiltration, immune checkpoint inhibitor targets, and efficacy of common drugs. Conclusions The constructed M0RG-based risk model may be promising for the clinical prediction of prognoses and therapeutic responses in patients with HCC

Neuropsychiatric events in an adult patient with influenza a (H3N2) treated with oseltamivir (Tamiflu): a case report

Abstract Background Total four influenza pandemics have happened since twentieth century, and currently influenza is in the seasonal epidemic around the world, with a sharp increase in its incidence each year. As an effective treatment of influenza infection, the use of oseltamivir is climbing globally. However, there have been reports of neuropsychiatric events associated with the drug, mainly in young patients and males. To our knowledge, this is the first reported case of oseltamivir-associated neuropsychiatric events occurring in an patient over 50-year-old. Case presentation Here we present the case of a 57-year-old Chinese female with H3N2 influenza infection who developed abnormal psychiatric symptoms after administration of high doses of oseltamivir. The patient recovered completely within the cessation of oseltamivir. Conclusions We hope that our case report will lead clinicians to be mindful about oseltamivir’s potential neuropsychiatric side effects, and to pay special attention to each patient’s mental state, both in children and adults

The efficacy and safety of direct-acting antiviral regimens for end-stage renal disease patients with HCV infection: a systematic review and network meta-analysis

BackgroundHepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making.MethodsWe conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods.ResultsOur search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%−100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%−100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%−99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%−100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%−61.5%) in HCV-infected ESRD patients.ConclusionThe G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359

Neuroimmune modulation in liver pathophysiology

Abstract The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area

Abnormal generation of IL-17A represses tumor infiltration of stem-like exhausted CD8+ T cells to demote the antitumor immunity

Abstract Background Variated anti-cancer therapies are combined with immune checkpoint blockades (ICBs) for improving ICB therapeutic efficacy. Occurrence of tissue damage is common that triggers multiple inflammatory cytokine generation. Gastrointestinal organs are the commonly affected. We investigated the impact of acute colitis on tumor infiltration of antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) for controlling tumor growth and responding to antibody against PD-1 (anti-PD-1). Methods Several tumor cell lines were inoculated into syngeneic mice subcutaneously or intra-hepatically. When tumor mass formed, activated CTLs were intravenously transferred into the tumor-bearing mice, that were given the drinking water containing 2% dextran sulfate sodium (DSS) for acute colitis induction. Tumor growth, infiltration of two exhausted CTL subsets, and the CTL interaction with tumor vascular endothelium were examined. Results Acute colitis dampened CTL-mediated antitumor effects, correlating with IL-17A elevation in the inflamed intestine. In the tumor bed, stem-like exhausted CTLs, which were defined as PD-1+Slamf6+Tim3−, expressed higher IL-17A receptor heterodimers and lower leukocyte function-associated antigen-1 (LFA-1) than terminally exhausted CTLs did, that were defined as PD-1+Slamf6−Tim3+. IL-17A stimulation reduced LFA-1 surface expression on stem-like exhausted CTLs and the counterpart ICAM-1 (intracellular adhesion molecule-1) on tumor vascular endothelium. IL-17A stimulation suppressed the extravasation across tumor vascular endothelium and self-renewal of stem-like, not the terminally exhausted CTLs. Administration of anti-IL-17A neutralizing antibody to the colitis mice restored the CTL tumor infiltration and enhanced anti-PD-1 treatment efficacy against tumors. In 33 hepatocellular carcinoma patients being treated with anti-PD-1 plus antibody against vascular endothelial growth factor, disease progression of 15 patients, that exhibited serum IL-17A increase 24 h post-therapy as compared to pre-therapy level, was poorer than that of 18 patients that exhibited serum IL-17A no-increase. Conclusions Abnormal generation of IL-17A mainly repressed tumor infiltration of stem-like exhausted CTLs. ICB-based immunotherapeutic efficacy could be upgraded with administration of anti-IL-17A, when treatment-related IL-17A elevation occurred due to tissue damage, such as acute colitis