Purpose. The aim of this study was to evaluate the diagnostic and prognostic value of IL-6 and sTREM-1 in the course of SIRS and sepsis in children with reference to routinely used CRP and PCT. Methods. A prospective study included 180 patients at the ages from 2 months to 18 years hospitalized due to fever from November 2015 to January 2017. Forty-nine children without fever hospitalized due to noninfectious causes formed the control group. IL-6 and sTREM-1 serum concentrations were assessed with the enzyme-linked immunosorbent assay method. Results. The mean serum concentrations of all the analyzed biomarkers were statistically significantly higher in the study group compared to the control group. Mean IL-6, sTREM-1, and PCT serum concentrations were statistically significantly higher in the group of patients with SIRS/sepsis compared to the group of feverish patients without diagnosed SIRS (N-SIRS). Based on the ROC curve analysis, it was shown that of all the biomarkers tested, only two—IL-6 and procalcitonin—had potential usefulness in the diagnosis of SIRS/sepsis in children with fever. Conclusion. Elevated levels of IL-6 and PCT are important risk factors for the development of SIRS/sepsis in children with fever. It seems that elevated IL-6 baseline serum level may predict a more severe course of febrile illness in children, because based on the ROC curve analysis, it was found that IL-6 is a statistically significant prognostic marker of prolonged fever≥3 days and prolonged hospitalization>10 days. The assessment of the usefulness of sTREM-1 in the diagnosis of SIRS/sepsis in feverish children requires further research.

IL-28B polymorphisms are predictors of response to therapy in adults infected with hepatitis C. We do not know whether they are markers of response to therapy in children and adolescents. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the IL-28B gene could influence the probability of response to therapy compared with other known baseline prognostic factors and correlate with clinical findings in pediatric patients infected with hepatitis C virus (HCV) genotypes 1 or 4. We determined three SNPs of IL-28B (rs12979860, rs12980275, and rs8099917) in 82 patients with chronic HCV infection treated with pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Treatment response and clinical data were analyzed. Overall, sustained virological response (SVR) was achieved by 45 % of patients infected with difficult-to-treat HCV genotypes 1 and 4. Except for IL-28B polymorphisms, there was no association of SVR with any other clinical data. IL-28B rs12979860 CC [odds ratio (OR), 6.81; p = 0.001] and rs8099917 TT (OR, 3.14; p = 0.013) genotypes were associated with higher SVR rates. IL-28B rs12980275 was not significantly associated with SVR (p = 0.058). Only the distribution between CC and CT–TT genotypes of rs12979860 significantly differentiated patients achieving early virological response (EVR) (OR, 10.0; p = 0.011). Children with the rs12979860 CC genotype had significantly higher baseline viral load compared with CT–TT patients (p = 0.010). In children and adolescents chronically infected with HCV genotypes 1 and 4, IL-28B rs12979860 and rs8099917 polymorphisms were the only predictors of response to peg-IFN/RBV.

The number of hepatitis C virus (HCV) infection cases is relatively low in children. This low number may be connected with the lack of screening tests and the asymptomatic course of infection. Currently, mother-to-infant transmission is the most common cause of HCV infection amongst children in developed countries. It is important to introduce routine screening tests for HCV in pregnant women. The risk of vertical transmission of HCV is estimated at approximately 5% (3%-10%). Currently, we do not have HCV transmission prevention methods. Some factors could potentially be eliminated by elective caesarean section. Currently, the method of prevention of perinatal HCV infection is the early identification and effective treatment of infections in young women in the preconception period. We describe genetic tests (IL-28B single nucleotide polymorphisms) to identify children with an increased chance of spontaneous clearance or sustained virologic response achievement and vitamin D level as a potential predictor of treatment response in children. It is also important to develop non-invasive tests that can predict liver fibrosis. The existence of differences in the mechanisms leading to liver injury between children and adults creates new perspectives of action to reduce liver disease progression in children in the early years of life.

Hepatitis C virus infection in children in the era of direct-acting antiviral

Global gene expression in liver transcriptome varies among cattle breeds. The present investigation was aimed to identify the differentially expressed genes (DEGs), metabolic gene networks and metabolic pathways in bovine liver transcriptome of young bulls. In this study, we comparatively analyzed the bovine liver transcriptome of dairy (Polish Holstein Friesian (HF); n = 6), beef (Hereford; n = 6), and dual purpose (Polish-Red; n = 6) cattle breeds. This study identified 895, 338, and 571 significant (p < 0.01) differentially expressed (DE) gene-transcripts represented as 745, 265, and 498 hepatic DE genes through the Polish-Red versus Hereford, Polish-HF versus Hereford, and Polish-HF versus Polish-Red breeds comparisons, respectively. By combining all breeds comparisons, 75 hepatic DE genes (p < 0.01) were identified as commonly shared among all the three breed comparisons; 70, 160, and 38 hepatic DE genes were commonly shared between the following comparisons: (i) Polish-Red versus Hereford and Polish-HF versus Hereford; (ii) Polish-Red versus Hereford and Polish-HF versus Polish-Red; and (iii) Polish-HF versus Hereford and Polish-HF versus Polish-Red, respectively. A total of 440, 82, and 225 hepatic DE genes were uniquely observed for the Polish-Red versus Hereford, Polish-HF versus Hereford, and Polish-Red versus Polish-HF comparisons, respectively. Gene ontology (GO) analysis identified top-ranked enriched GO terms (p < 0.01) including 17, 16, and 31 functional groups and 151, 61, and 140 gene functions that were DE in all three breed liver transcriptome comparisons. Gene network analysis identified several potential metabolic pathways involved in glutamine family amino-acid, triglyceride synthesis, gluconeogenesis, p38MAPK cascade regulation, cholesterol biosynthesis (Polish-Red versus Hereford); IGF-receptor signaling, catecholamine transport, lipoprotein lipase, tyrosine kinase binding receptor (Polish-HF versus Hereford), and PGF-receptor binding, (Polish-HF versus Polish-Red). Validation results showed that the relative expression values were consistent to those obtained by RNA-seq, and significantly correlated between the quantitative reverse transcription PCR (RT-qPCR) and RNA-seq (Pearson’s r > 0.90). Our results provide new insights on bovine liver gene expressions among dairy versus dual versus beef breeds by identifying the large numbers of DEGs markers submitted to NCBI gene expression omnibus (GEO) accession number GSE114233, which can serve as useful genetic tools to develop the gene assays for trait-associated studies as well as, to effectively implement in genomics selection (GS) cattle breeding programs in Poland.