Effect of immunogenetics polymorphism and expression on direct-acting antiviral drug response in chronic hepatitis C.

The prevalence of HCV infection in Egypt has decreased following the introduction of direct-acting antiviral therapy. However, treatment response is influenced by various factors, particularly host immunogenetics such as IL-28B and FOXP3 polymorphisms. The current study examined the impact of SNPs in the FOXP3 gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved 99 HCV patients who achieved SVR12 after a 12 week DAA treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, FOXP3 rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and FOXP3 were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T > C (P = 0.013) and FOXP3 rs2232365 A > G polymorphisms (P = 0.008) were found to significantly increase the risk of non-response. Responders had higher IL28B serum levels (P = 0.046) and lower FOXP3 levels (P < 0.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and FOXP3 rs2232365 with treatment response, independent of age and gender. A predictive model was developed with 76.2% sensitivity and 91.9% specificity for estimating DAAs response in HCV patients.Our findings confirmed the IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. Our results may lead to new insights into DAA responsiveness contributing to personalized medicine and improving therapeutic decision-making for HCV patients.

Evaluation of ABCA1 gene polymorphism as a prognostic index of fibrosis progression in NAFLD patients.

INTRODUCTION: It had been evident that non-alcoholic fatty liver disease (NAFLD) is the new era epidemic. Despite emergence of many drugs on the pipeline that considered candidates to cure NAFLD/NASH, the critical need for defining the cohort liable to fibrosis progression is yet unmet. AIM: Evaluate ABCA1 (rs1800977) genotyping as a noninvasive predictor of liver fibrosis severity. MATERIALS AND METHODS: This study included 118 liver biopsy-proven NAFLD-patients. According to Metavir-fibrosis-staging, cases were divided to early fibrosis (74 cases), and 44 cases with significant fibrosis (>F2), added to 49 healthy control subjects. All patients were subjected to liver function tests, lipids profile, triglyceride TG index, and hepatic steatosis index (HSI) and real-time PCR ABCA1 SNP (rs1800977). RESULTS: Significant differences in transaminases (p > .05), albumin (p < .009), cholesterol (p0.03), low density lipoproteins (LDL) (0.006), triglycerides (p < .001), HSI (p < .001), FIB4 (p < .001) and APRI (p < .001) were reported in those with significant than early fibrosis and control groups. CC was the most prevalent in significant (36.4%) than early fibrosis (13.5%) and control groups (8.2%), with prevalence of C allele in significant fibrosis (p ≤ .003). Univariate analysis revealed that DM (p ≤ .001), TG index (p ≤ .022), cholesterol (p ≤ .03), HSI (p ≤ .006), LDL (p ≤ .02), HDL (p ≤ .01), APRI (p ≤ .02) and CC genotype (p ≤ .005) were the main factors affecting fibrosis progression in NAFLD. However multivariate analysis proved only the role of HSI (p ≤ .005), LDL (p ≤ .02), HDL (p ≤ .003) and CC genotype (p ≤ .03) in predicting fibrosis severity. CONCLUSION: Dyslipidemias, hepatic steatosis index and ABCA1 (rs1800977) gene polymorphism CC genotype; were the only independent predictors of advanced fibrosis in NAFLD-patients.

Value of IFNL3 genetic polymorphism in the prediction of HCV treatment response to direct-acting antiviral drugs versus interferon therapy.

Background: Despite the outstanding results of direct-acting antiviral therapies (DAAs) of Hepatitis C infection (HCV), non-responders had to be more defined. Aim: assess the outcome of DAAs in linkage with Interferon lambda 3 (IFNL3) in HCV patients. Methods: This case-control-study was conducted on 495 chronic-HCV (genotype-4a), previously treated Egyptians by either DAAs (responders 195, 120 relapsers) or interferon/ribavirin (IFN/RBV) (140 responders, 60 relapsers), and 98 healthy controls. IFNL3 distribution, clinical and laboratory data were assessed. Results: CT was the most predominant genotype in Egyptians (51%). All genotypes were sensitive to DAAs mainly CT genotype (60%), even TT genotype (resistant to IFN/RBV 40%) had 29.2% sensitivity. CT genotype was predominant in sofosbuvir/Daclatasvir responders (67.6%) (OR = 0.66), while non-CT prevailed in relapsers (56.7%). TT genotype may respond to SOF/Ledi better than other regimens (66.7%). In IFN/RBV relapsers; CT genotype was commoner (50%) than others, while CC genotype predominated in responders (54.3%). The c allele was the commonest in responders to IFN/RBV (71.4%), while the T allele was resistant to treatment (65% in relapsers). Addition of RBV to SOF/DCV reported higher resistance with CT genotype (42.2%-50%) and TT genotype (17.8%-27.8%). Conclusion: This study recommended IFNL3 genotyping to be a prerequisite before stratifying treatment for HCV-4a Egyptians.

Circulating microRNA-301 as a promising diagnostic biomarker of hepatitis C virus-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious consequence of persistent hepatitis C virus (HCV) infection and represents one of the most aggressive neoplasms globally. The implication of microRNA-301 (miR-301) in the initiation and progression of different types of cancers has been proved. We aimed to assess circulating microRNA-301 as possible biomarker for the early detection of HCC in patients with chronic HCV infection. miR-301 expression levels were estimated in plasma samples of 42 patients with newly diagnosed HCV-related HCC, 48 chronically HCV infected patients with liver cirrhosis and 40 healthy individuals by reverse transcription-quantitative polymerase chain reaction technique. In comparison with chronically HCV infected patients and healthy controls, miR-301 expression levels were significantly increased in HCC patients (P < 0.001). miR-301 levels distinguished HCC patients from chronic HCV patients, with area under the receiver-operating characteristic curve of 0.89 (95% CI 0.82-0.96), the sensitivity and the specificity were 78.57% and 89.58% respectively. Moreover, miR-301 levels were significantly linked with tumor size (P = 0.014), serum levels of alpha-fetoprotein (AFP) (P = 0.028) and Barcelona Clinic Liver Cancer (BCLC) score (P = 0.003). These results reveal that miR-301 can serve as a promising non-invasive biomarker for diagnosis of HCC in chronically HCV infected patients.