Picolinic Acid in Patients with Chronic Hepatitis C Infection: A Preliminary Report

Macrophage activation seems to be a feature of chronic liver diseases. Picolinic acid (PA) as a macrophage secondary signal causes the activation of interferon-gamma- (IFN-γ-) prime macrophage and triggers cytokine-driven inflammatory reactions. The rationale for seeking increased PA formation in chronic viral hepatitis is based on the involvement of activated macrophages in chronic viral hepatitis-associated inflammation. The aim of this study was to determine serum PA levels in patients with chronic hepatitis C infection, taking into account the presence of diabetes. We assessed PA and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation in 51 patients with chronic hepatitis C infection (CHC), both with and without diabetes and 40 controls. Compared with the controls, the patients with CHC showed a significant increase in plasma concentrations of PA and hsCRP (P < 0.01 and P < 0.05, resp.). The values of PA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were between PA and hsCRP levels (P < 0.05) and the presence of diabetes (P < 0.001). We documented that significant elevation in serum PA levels is associated with diabetes prevalence and increased inflammatory response reflected in hsCRP levels in CHC patients

SARS-CoV-2 infection: etiopathogenesis, clinical picture, current therapeutic options – the author’s observations

Currently, the scenario of a self-contained disappearance of the epidemic (as it was in the case of SARS) is no longer taken into consideration, whilst the SARS-CoV-2 virus will stay with us forever, similarly to other coronaviruses or flu. It is quite likely that periodical exacerbations of the epidemics – their growth and decrease – depend on many factors, which comprise, among others, the approval of the restrictions by the society or the manner in the epidemiological supervision is carried out and whether it is consistent. We must be ready for about 18–24 months of a high activity of COVID-19 with periodic active hot spots in many world regions. This requires efficient health services and the access to efficacious medication. Without an effective prophylactic vaccine, it seems that we will not be able to prevent the spread of the pandemi

Understanding the long-term interplay of SARS-CoV-2 immune and inflammatory responses with proteases in COVID-19 recovery: a longitudinal study

IntroductionThe immune and inflammatory responses following SARS-CoV-2 infection, particularly in the context of long COVID, remain critical areas of study. Understanding these responses is essential for addressing the long-term health impacts of COVID-19. Recent research also highlights the pivotal role of proteases in modulating immune responses and contributing to disease severity, making them a key focus of our analysis.MethodsWe conducted a longitudinal analysis of 72 convalescent COVID-19 patients, assessing recovery at three key time points: immediately post-discharge, one month later, and three months post-infection. Additionally, a subset of 15 patients was followed up two years post-COVID-19. Clinical parameters, including demographics, comorbidities, treatment modalities, and COVID-19 severity, were evaluated. Using CyTOF technology, we characterized over 30 immune cell subsets, including granulocytes, T cells, B cells, NK cells, and monocytes. We also performed multiplexed analyses of blood samples to profile cytokines, chemokines, growth factors, proteases, and COVID-19-related proteins.ResultsOur comprehensive approach revealed significant changes in the immune system over time, highlighting the role of specific immune cells and proteases in the recovery process. Key findings include a decreasing deregulatory effect on immune responses exerted by subsequent SARS-CoV-2 variants Alpha, Delta, and Omicron.ConclusionThis study provides an in-depth understanding of the molecular dynamics of immune recovery following COVID-19. By integrating clinical profiling, plasma multiplex analysis, antibody profiling, mass cytometry immunophenotyping, in vitro PBMC stimulation, and the role of proteases, we offer valuable insights into the complex interplay of immune, inflammatory, and protease-mediated responses in individuals recovering from COVID-19

Genome Wide Association Study Identifies Genetic Variants Associated With Early And Sustained Response To (Peg)Interferon In Chronic Hepatitis B Patients: The GIANT-B Study

(Peg)interferon ((Peg)IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Direct acting antivirals therapy and hepatocellular carcinoma risk in patients with hepatitis C virus

The estimated number of people with active hepatitis C virus infection worldwide is about 70 million. The estimated number of people with active hepatitis C virus infection worldwide is about 70 million. Approximately 30% of infected individuals develop cirrhosis, whilst some develop liver cancer, the fifth most common cancer worldwide. Currently available treatments, high-efficacy antiviral agents mostly short-term (8-12 weeks) and pangenotypic, have efficacy rates of over 96%. Some patients, especially those with cirrhosis, develop primary liver cancer even after effective hepatitis C virus treatment. In order to diagnose hepatocellular carcinoma early, patients at risk should be enrolled in a surveillance program