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.

Long Non-Coding RNAs ASB16-AS1 and AFAP1-AS1: Diagnostic, Prognostic Impact and Survival Analysis in Colorectal Cancer.

Background: We aimed to evaluate the diagnostic roles of AFAP1-AS1 and ASB16-AS1 in colorectal cancer and highlight their roles in predicting colorectal cancer patients' prognosis. Methods: In this case-control study, 146 participants were involved. Group I included 47 patients with CRC. Group II composed of 49 patients with benign lesions in the colon, and Group III included 50 apparently normal subjects of coincided age and gender as controls. All participants were subjected to clinical and endoscopic evaluations, CA19-9, CEA, and quantification of relative expression of lncRNAs ASB16-AS1 and AFAP1-AS1. Results: CRC patients had significantly elevated expression levels of both lncRNAs in tissue and plasma samples versus benign and control groups (p < 0.001). Despite the higher sensitivity of tissue samples results, the relative expression of both lncRNAs in plasma samples was very encouraging in the discrimination between patients with CRC versus control and benign groups. Furthermore, both lncRNAs could discriminate patients with early-stage CRC (stage I&II) from being colonic lesion and control groups with better sensitivity and specificity presented by ASB16-AS1 in tissue and plasma than results detailed by AFAP1-AS1. High expression levels of ASB16-AS1 in tissue and plasma and tissue lncRNA AFAP1-AS1 are significantly correlated with decreased overall survival (p < 0.001) and reduced progression-free (p < 0.001) compared to low expression in CRC patients. Conclusion: We propose the utilization of lncRNA ASB16-AS1 and lncRNA AFAP1-AS1 as biomarkers in diagnosis and prognosis estimation for CRC patients. Moreover, their value in early CRC patients may affect the assortment of target therapy and treatment protocols.

Evaluation of MicroRNA-122 as a Biomarker for Chronic Hepatitis C Infection and as a Predictor for Treatment Response to Direct-Acting Antivirals.

BACKGROUND: Treatment response to antiviral drugs is a challenging issue in patients with chronic hepatitis C virus (HCV) infection. Although microRNA-122 represents the majority of the microRNA content in hepatic tissues, few studies have evaluated its role in the treatment response, so we aimed to study its role in chronic HCV patients and in predicting the treatment response to direct-acting antivirals (DAAs). METHODS: The study included 125 chronic HCV patients (89 naïve and 36 with a prior failed peginterferon/ribavirin response) and 50 apparently healthy subjects. Complete blood count, liver function, α-fetoprotein, lipid profiles, serum creatinine, abdominal ultrasound, and FibroScan® were assessed. Viral markers, HCV antibodies, and hepatitis B surface antigen were measured by enzyme-linked fluorescent immunoassay, with quantitative estimation of HCV RNA and microRNA-122 levels by real-time PCR. RESULTS: The microRNA-122 level in HCV patients (those with a sustained virologic response 12 weeks after finishing therapy [SVR12] and non-responders) was significantly increased compared with controls and expressed more in non-responders versus SVR12 (p=0.042). ROC curve analysis of microRNA-122 for differentiating HCV patients from healthy controls revealed that a cut-off point of >1.45 had a sensitivity of 67.20%, specificity of 94.0%, AUC=0.861, and p<0.001; and for predicting response to treatment a cut-off point ≤5.66 could significantly (p=0.022) predict the occurrence of SVR, with a sensitivity of 60.34%, specificity of 66.67%, and AUC=0.729. Logistic regression analysis showed significant values for microRNA-122 in multivariate and univariate analysis for the prediction of response to DAAs. CONCLUSION: The results demonstrated the possible function of microRNA-122 as an indicative tool for distinguishing chronic HCV patients from controls and in the assessment of the therapeutic reaction to DAAs.