Chronic hepatitis B (CHB) has a wide range of outcomes depending on host immune responses mainly Toll-like receptors (TLRs) signaling and released cytokines. Toll-like receptor 2 (TLR2) single nucleotide polymorphisms (SNPs) and interleukin 6 (IL-6) may influence the course of CHB. We aimed to elucidate the relation between TLR-2 polymorphism, IL-6 profile, and CHB progression. We analyzed TLR-2 polymorphism (SNP; rs3804099) in 185 CHB patients and 60 controls using TaqMan allelic discrimination assay. Serum IL-6 levels were assessed by ELISA. IL-6 levels were considerably higher in active CHB and cirrhotic patients compared with inactive carriers and controls (P < 0.001). IL-6 showed positive correlation with ALT and advanced fibrosis in active CHB patients (r = 0.31,P = 0.02). A significant positive correlation was noticed between IL-6 and HBV DNA PCR in all CHB groups. TT genotype of rs3804099/TLR-2 was significantly more prevalent in inactive carriers compared to active hepatitis patients (P = 0.04, OR = 0.39 and 95% CI: 0.16–0.95). Both heterozygous CT and mutant TT genotypes were significantly more frequent among inactive carriers compared to cirrhotic patients (P = 0.01, OR = 0.33, 95% CI: 0.13–0.81 andP = 0.009, OR = 0.32, 95% CI: 0.13–0.77). TT genotype was significantly related to lower IL-6 levels in active hepatitis and cirrhotic groups (P = 0.005 andP = 0.001, respectively) showing that TLR mutations would be associated with milder hepatitis activity and lower possibility for disease progression. There may be a positive association between TLR2 rs3804099 polymorphism and hepatitis B activity. IL-6 is a good indicator of CHB disease progression.

Background and Aim: A wide range of clinical manifestations and outcomes, including liver injury, have been reported in COVID-19 patients. We investigated the association of three substantial gene polymorphisms (FURIN, IFNL4, and TLR2) with COVID-19 disease susceptibility and severity to help predict prognosis. Methods: 150 adult COVID-19-assured cases were categorized as follows: 78 patients with a non-severe presentation, 39 patients with severe disease, and 33 critically ill patients. In addition, 74 healthy controls were included. Clinical and laboratory evaluations were carried out, including complete and differential blood counts, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin, ferritin, interleukin-6 (Il-6), and liver and kidney functions. FURIN (rs6226), IFNL4 (rs12979860), and TLR2 (rs3804099) genotyping allelic discrimination assays were conducted using real-time PCR. Results: The FURIN, IFNL4, and TLR2 genotypes and their alleles differed significantly between COVID-19 patients and controls, as well as between patients with severe or critical illness and those with a non-severe presentation. According to a multivariable regression analysis, FURIN (C/T + T/T) and TLR2 (T/C + C/C) mutants were associated with COVID-19 susceptibility, with odds ratios of 3.293 and 2.839, respectively. FURIN C/C and IFNL4 T/T mutants were significantly linked to severe and critical illnesses. Multivariate regression analysis showed that FURIN (G/C + C/C) genotypes and IFNL4 T/T homozygosity were independent risk factors associated with increased mortality. Conclusion: FURIN, IFNL4, and TLR2 gene variants are associated with the risk of COVID-19 occurrence as well as increased severity and poor outcomes in Egyptian patients.

Hepatitis C virus (HCV) is the predominant viral cause of hepatocellular carcinoma (HCC). Early detection and use of reliable biological markers can improve survival for HCC patients. MiR-485-5p was identified as a tumor-suppressing microribonucleic acid (miRNA) in some human cancers and was recently found to be downregulated in HCC tissues, signifying its utility as a promising biomarker. We aimed to investigate the potential role of circulating miR-485-5p as a novel diagnostic and prognostic biomarker for HCV-related HCC. This case–control study included 50 patients with HCC associated with HCV, 50 patients with HCV-related liver cirrhosis, and 50 healthy controls. History gathering, physical examination, laboratory, and imaging assessments were performed. A quantitative real-time polymerase chain reaction was used to measure miR-485-5p levels. Serum miR-485-5p values demonstrated a stepwise decline pattern from the control group to cirrhotic patients, with the HCC group exhibiting the lowest levels ( p < 0.001). HCC patients with early BCLC stages had significantly lower miR-485-5p levels than those with late stages ( p = 0.004). The miR-485-5p displayed a better performance in predicting HCV-related HCC with a greater area under the ROC curve (AUC) than alpha-fetoprotein (AFP) (AUC and sensitivity 0.921 and 92.0 versus 0.704 and 64.0, respectively) ( p < 0.001). Also, its performance in predicting HCC prognosis surpassed that of AFP (AUC and sensitivity 0.872 and 85.19 versus 0.695 and 62.96, respectively) ( p < 0.001). Circulating miR-485-5p is a promising, accurate, and noninvasive biomarker for the early detection and prediction of prognosis in patients with HCV-linked HCC.

Background: As physicians in a referral hospital, we observed the association between history of enteric fever and somatic disorders associated with low mood. At the Al-Hussein University Hospital, Cairo and the National Liver Institute Hospital, Menoufia, we receive patients from all over Egypt, including rural areas where enteric fever is endemic. Aim: Here in, 60 Egyptian patients referred to us for evaluation of different somatic disorders are reported. Methods: After extensive evaluations, the patients’ symptoms were function-related. Also, their typhoid carrier states were documented, and the severity of depression using Hamilton-D (HAM-D) questionnaire was evaluated and recorded. All patients were treated with ceftriaxone, 2 gm, IV, daily for 15 days. The clinical evaluation and Hamilton score were reassessed at the end of the treatment and 6 weeks thereafter. The patients did not receive any anti-depressant nor anti-anxiety treatment during their course. Typhoid carrier was defined by documenting the history of typhoid fever that was diagnosed by culturing the Salmonella species, and not by serology, isolated from stool culture along with febrile condition, plus the absence of fever in the past 3 weeks. The Widal test was not accepted as a criterion for enrollment. Results: Patients showed clinically significant improvement in the somatic complaints, and their HAM-D score immediately post-treatment that was consolidated for 6 weeks post-treatment completion. Conclusion: In this study, the typhoid carrier was associated with the psychosomatic depression that improved by antibiotic therapy.

Background: Circulating platelet-derived growth factor receptor-β (PDGFRβ) has recently been found to correlate with severity of liver disease in multiple etiologies, including liver steatosis. In diabetic patients with metabolic-associated fatty liver disease (MAFLD), widely used non-invasive scoring systems, particularly the fibrosis-4 (FIB-4) score, showed unsatisfactory performance in predicting liver fibrosis severity. The aim of this study was to evaluate the productivity of serum PDGFRβ as a non-invasive biomarker of liver fibrosis in diabetic MAFLD patients. Methods: This was a population-based case-control study conducted on 50 diabetic MAFLD patients, 40 nondiabetic MAFLD patients, and 40 healthy controls. All subjects underwent complete history taking, clinical examination, anthropometric measurements, bioelectrical impedance analysis (BIA), and laboratory tests, including the PDGFRβ assay. Hepatic steatosis was assessed with magnetic resonance imaging (MRI), along with magnetic resonance elastography (MRE) for the assessment of liver fibrosis. The diagnostic performance of PDGFRβ as well as PDGFRβ + FIB-4 in prediction of significant liver fibrosis in diabetic MAFLD patients was assessed. Results: Liver steatosis and significant liver fibrosis (≥ F2) were significantly higher in diabetic MAFLD patients than in nondiabetics. PDGFRβ levels were significantly higher in both diabetic and nondiabetic MAFLD patients compared to controls. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PDGFRβ to predict significant liver fibrosis in diabetic MAFLD patients were 85%, 93.33%, 89.5%, and 90.3%, respectively, at a cutoff > 2.54, and were 85.71%, 51.52%, 27.3%, and 94.4% at a cutoff > 1.59 in nondiabetics. Sensitivity, specificity, PPV, and NPV of (PDGFRβ at a cutoff > 2.54 + FIB-4 at a cutoff > 1.17) to predict significant liver fibrosis in diabetic MAFLD patients were 100%. PDGFRβ was the only independent predictor of significant liver fibrosis in diabetic MAFLD (p = 0.006). Conclusions: PDGFRβ proved efficacy as a noninvasive biomarker in the prediction of significant liver fibrosis (≥ F2) in diabetic MAFLD patients.

Background: Cirrhosis results from chronic liver injury. Chemokines have a central role in modulating immune activity. The Duffy Antigen Receptor for Chemokines (DARC), functioning as a decoy receptor, helps maintain chemokine balance in the bloodstream. Objective: To explore how the DARC rs12075 (125A > G; Asp42Gly) genetic variation relates to liver fibrosis progression in chronic hepatitis patients. Methodology: A case-control design was employed. The study included 80 patients with chronic hepatitis C or B (40 with cirrhosis, 40 without) and 40 matched healthy individuals as controls. All participants underwent routine diagnostic procedures and liver fibrosis assessment via FibroScan. The rs12075 polymorphism was genotyped using real-time PCR. Results: The GG genotype was less frequent in the cirrhotic group compared to other groups. Furthermore, a lower frequency of liver cirrhosis was observed in the dominant genetic model (GG+AG versus AA genotypes). The G allele was notably underrepresented among cirrhotic patients (25%) compared to both non-cirrhotics (40%) and controls (41.3%), showing a potential protective association (ORs of 0.5 and 0.47, p = 0.043 and p = 0.029, respectively). Conclusion: The DARC rs12075 polymorphism may influence fibrosis advancement in chronic viral hepatitis. The G allele potentially offers a protective effect against cirrhosis.