FURIN, IFNL4, and TLR2 gene polymorphisms in relation to COVID-19 severity: a case-control study in Egyptian patients.

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.

Toll- like receptor 2 polymorphism and IL-6 profile in relation to disease progression in chronic HBV infection: a case control study in Egyptian patients.

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 and P = 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 and P = 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.

Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients.

Aim of the study: Despite the ample flow of non-alcoholic fatty liver disease (NAFLD) drugs in the pipeline, lifestyle modifications are still the optimal solution of NAFLD. The aim of the study was to assess short term effects of Ramadan fasting (RF) as a sort of intermittent fasting (IF) on biochemical, radiological, and anthropometric parameters of NAFLD patients. Material and methods: Ninety-eight NAFLD patients were recruited and voluntarily subjected to 16 hours daily fasting for an average of 22-29 days, without special dietary recommendations. Anthropometric, laboratory and radiological parameters were measured before, at 30 days, and one month after fasting (fasting and non-fasting phases). Results: Patients were mostly rural (76%), hypertensive (34.7%), diabetic (43.9%), and female (76.8%), with overt criteria of metabolic syndrome (67.3%). Liver transaminases (ALT and AST) were ameliorated significantly after fasting (p ≤ 0.01), which continued in the following month (p ≤ 0.01) especially in those with elevated ALT before fasting (46%). Eleven patients (24.4%) experienced ALT normalization after one month of fasting, which was further increased to 15 (33.3%) one month later. Lipid profiles (cholesterol, triglycerides, HDL, LDL, cholesterol/HDL risk ratio) were significantly corrected following IF (p ≤ 0.01) and continuing in the next phase (p ≤ 0.010). Body mass index (BMI) lessened following the fasting (p ≤ 0.01), while no remarkable changes were noted regarding waist, hip, and triceps skin fold thickness (p ≤ 0.01). Glycemic indices (HbA1c, postprandial, HOMA-IR) and fibrosis markers (FIB-4 and APRI) were significantly ameliorated (p ≤ 0.01), while reduction in inflammatory markers was not long lasting (p ≤ 0.01). Conclusions: Intermittent fasting led to momentous improvements in ultrasonographic, biochemical, and anthropometric parameters of NAFLD especially in early phases and prediabetics.