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.

Early fibrosis regression by shear wave elastography after successful direct-acting anti-HCV therapy.

Shear wave elastography (SWE) is a noninvasive ultrasound-based marker of hepatic fibrosis not requiring a special device. Successful direct-acting anti-HCV therapy was associated with hepatic fibrosis regression assessed by transient elastography (FibroScan). Data on the utility of SWE in these patients and how early fibrosis can regress after treatment are still lacking. To assess liver fibrosis by SWE before and after direct-acting antiviral treatment of chronic hepatitis C (CHC), we enrolled 165 CHC genotype 4 Egyptian patients treated with different Sofosbuvir-based regimens. Patients' laboratory characteristics, fibrosis biomarkers, namely Fibrosis-4 (FIB-4) index and AST/platelet ratio index (APRI) and liver stiffness measurements (LSM) by SWE were evaluated at baseline, end of treatment (EOT at week 12), week 24 and week 36. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as FIB-4 and APRI indices decreased significantly at EOT, week 24 and week 36 in comparison to baseline (P value < 0.001). Although platelet counts did not significantly differ between baseline and EOT, they increased significantly from EOT to week 24 and week 36 with a P value < 0.001. The mean LSM showed improvement at EOT (7.01 ± 3.59 kpa), week 24 (6.18 ± 3.39 kpa) and week 36 (5.74 ± 3.21 kpa) in comparison to baseline (8.49 ± 0.83 kpa) (P value < 0.001). There is early liver fibrosis regression at EOT and throughout the time after successful treatment with direct-acting antiviral agents (DAAs). SWE is a feasible, easily applicable noninvasive relatively inexpensive assessment method of liver fibrosis.

On-treatment improvement of an emerging psychosomatic depressive disorder among salmonella carriers: a multicenter experience from Egypt.

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.

High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C.

BACKGROUND: Direct acting antivirals (DAAs) are highly effective for treatment of hepatitis C (HCV) but brand products are priced beyond the means of most low and middle income countries (LMICs). Although a few DAAs are offered at reduced prices in access programs, they are still beyond affordability in limited resource settings with a large HCV infected population. Cheap generics might fill this economic need, but studies comparing their clinical efficacy to that of original products are limited. AIM: To compare efficacy of brand and generic DAAs used in the national treatment program in Egypt. METHODS: HCV treatment eligible patients (n=971) were enrolled. They were treated with 12 weeks of either sofosbuvir-daclatasvir (SOF-DCV) or SOF-ledipasvir (SOF-LDV). Ribavirin (RBV) was added to patients with cirrhosis and to SOF experienced patients. Patients with cirrhosis who were RBV intolerant were treated for 24 weeks without RBV. RESULTS: Most patients were males (61.4%), treatment naïve (88.6%), without cirrhosis (61.7%), and the mean age was 51.3±11.31 years. Baseline characteristics were not different in patients treated with brand or generic medications regarding age, liver tests, creatinine, platelets, MELD score, baseline HCV-RNA and transient elastography. Overall sustained virologic response (SVR) rate was 98.1%, which was similar for generic and brand drugs (98.2% vs. 98.1%; p=1), and similar with both regimens used (SOF-DCV±RBV: brand: 98.1%, generic 97.8%; p=0.729, SOF-LDV±RBV: brand 98.2%, generic 100%; p=0.729). AST and ALT decreased significantly with initiation of therapy with both generic and original drugs. CONCLUSION: Generic and brand DAAs are equally effective for achieving SVR and improving aminotransferases.

Assessment of liver fibrosis with acoustic radiation force impulse imaging versus liver histology in patients with chronic hepatitis C: a pilot study.

BACKGROUND: Acoustic radiation force impulse imaging (ARFI) involves the mechanical excitation of tissues using short-duration acoustic pulses to generate localized displacements in tissue. The displacements results in shear-wave propagation, tracked by ultrasonography (US) correlation-based methods and recorded in meters per seconds. AIM: To compare (ARFI) integrated into a conventional US with the standard histological examination of liver biopsy specimens for the assessment of liver fibrosis. MATERIALS AND METHODS: Histological fibrosis staging with standard liver biopsy using the Metavir scoring system as well as fibrosis assessment using ARFI were performed to 80 patients with chronic hepatitis C over a 3-month period. RESULTS: ARFI findings were identical to the biopsy findings in 61 (76.25%) patients.Fifty-eight (67.5%) patients with an early fibrosis stage (F0, F1, and F2) by histology had identical fibrosis stages using ARFI.Only 20 out of 26 patients with an advanced fibrosis stage (F3 and F4) using ARFI had advanced fibrosis histologically. In the advanced fibrosis stages, the sensitivity of ARFI was 70% and specificity was 80%, with positive and negative predictive values of 53.8 and 88.9%, respectively. The accuracy of detection of advanced fibrosis by ARFI was 77.5%. CONCLUSION: ARFI imaging is a promising noninvasive US-based method for the assessment of liver fibrosis.