Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients.

Methods: In total, 170 chronic HBV patients and 50 healthy controls of comparable age and gender were included in this case-control study. Clinical, laboratory, and imaging evaluations were conducted. ELISA was used to determine serum IL-6 levels, and TLR2 (rs3804099) genotyping allelic discrimination assay was performed using real-time PCR. Results: IL-6 values were significantly higher in the HCC group, followed by the cirrhotic group, than those in chronic hepatitis and control groups (p < 0.001), with a significant correlation with disease activity and progression parameters. TRL2 homozygous TT was the most frequent in the control group, but the CC genotype was significantly more prevalent in the HCC group than that in the other groups. Furthermore, the CC genetic variant was associated with higher levels of IL-6 and viral load in all HBV patients, whereas the TT genotype was associated with larger tumor size. Multivariate regression analysis demonstrated that in chronic HBV patients, viral load and TRL2 polymorphism are independent risk factors associated with the progression from chronic hepatitis to liver cirrhosis and to HCC. Similarly, the HBV viral load (p=0.03, OR = 2.45, and 95% CI: 1.69-3.65), IL-6 levels (p=0.04, OR = 3.45, and 95% CI: 2.01-6.9), and TRL2 variants (p=0.01, OR = 4.25, and 95% CI: 2.14-13.5) are independent risk factors associated with disease progression from cirrhosis to HCC. Conclusion: In chronic HBV patients, TRL2 polymorphism and higher IL-6 levels were positively correlated with a higher likelihood of HCC and chronic hepatitis B disease activity and progression.

Association of XRCC1 p. Arg194Trp gene polymorphism with the risk of hepatocellular carcinoma in HCV Egyptian population: A pilot case-control study.

Background: Hepatocellular carcinoma (HCC) is the most common and fatal primary liver cancer. Genetic variants of DNA repair systems can reduce DNA repair capability and increase HCC risk. Objectives: This study aimed to examine, in Egyptian hepatitis C virus (HCV) patients, the relationship between the X-ray repair cross-complementing group 1 (XRCC1) rs1799782 single nucleotide polymorphism (SNP) and HCC susceptibility. Methods: We included 100 adult HCV-positive patients with HCC and 100 adult HCV-positive patients with liver cirrhosis as pathological controls. XRCC1 rs1799782 SNP genotyping was done in both groups using quantitative real-time PCR (qPCR). The distribution of genotypes in patients and controls was compared using several inheritance models. Results: We found that the CT genotype, when analyzed under both the co-dominant (OR (95 % CI): 2.147 (1.184-3.893), p = .012) and the over-dominant (OR (95 % CI): 2.055 (1.153-3.660), p = .015) models, as well as the combined CT and TT genotypes under the dominant model (OR (95 % CI) of 1.991 (1.133-3.497), p = .017), were associated with increased susceptibility to HCC. The frequency of the T allele was higher among HCC participants (32%) compared to those with cirrhosis (23.5%) and carrying the T allele increased the risk of HCC by 1.532 times, however, these associations did not reach statistical significance (p-values >0.05). Moreover, the variant T allele was associated with worse clinical manifestations and laboratory results among the HCC group, but AFP levels were not affected significantly. Conclusions: Egyptians with XRCC1 rs1799782 SNP may have a higher risk of HCV-related HCC. More extensive multi-center prospective investigations must confirm this association.

Angiotensin-Converting Enzyme-2 (ACE-2) with Interferon-Induced Transmembrane Protein-3 (IFITM-3) Genetic Variants and Interleukin-6 as Severity and Risk Predictors among COVID-19 Egyptian Population.

Introduction: The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity. Results: The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT + TT, odds ratio (95% confidence interval): 12.136 (2.784-52.896) and IFITM-3 rs12252 AG + GG: 17.276 (3.673-81.249), both p < 0.001. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (p < 0.001). Conclusion: ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.

Association between breakthrough infection with COVID-19 and Toxoplasma gondii: a cross-sectional study.

The breakthrough infection following COVID-19 vaccination has been a subject of concern recently. Evidence suggests that COVID-19 vaccine efficacy diminishes over time due to multiple factors related to the host, and vaccine. Coinfection with other pathogens was claimed earlier as a contributing cause for this phenomenon. Hence, we aimed to stratify the association of post-COVID-19 vaccination breakthrough coinfection with Toxoplasma gondii (T. gondii) and its impact on disease severity. This cross-sectional study included 330 COVID-19-vaccinated patients confirmed by RT-PCR. They were also screened for anti- T. gondii antibodies using ELISA. Toxoplasma seropositive cases' whole blood was screened for DNA using PCR to correlate results with COVID-19 severity. Out of 330 COVID-19 vaccinated patients with breakthrough infection, 34.5% (114 patients) showed positivity for Toxoplasma IgG by ELISA, and none of the cases was IgM positive. Eleven patients (9.6%) of the IgG-positive cases were positive by PCR. Positive PCR cases correlated positively with the Toxoplasma IgG titer (P < 0.001), and the Cutoff point was 191.5. Molecular analysis of Toxoplasma and COVID-19 severity showed that 8 (72.7%), 1 (9.1%), and 2 cases (18.2%) had mild, moderate, and severe courses of the disease, respectively, with no significant correlation. Our study reported a heightened prevalence of latent toxoplasmosis among mild cases of COVID-19 breakthrough infection. Nevertheless, a discernible correlation between latent toxoplasmosis and COVID-19 severity is lacking. Hence, implementing studies on a larger scale could provide a more comprehensive comprehension of this association.