Saudi Cultural Missions Theses & Dissertations
Permanent URI for this communityhttps://drepo.sdl.edu.sa/handle/20.500.14154/10
Browse
3 results
Search Results
Item Restricted DUAL BURDEN: HCV ANTIBODY POSITIVITY AND DEPRESSION DIAGNOSIS IN UNITED STATES ADULTS(New York University, 2024-06-24) Alserhani, Asma; Coyle, ChristianaBackground: Hepatitis C virus (HCV) infection and depression are significant public health concerns, with previous studies suggesting a complex relationship between the two conditions. This study aimed to investigate the association between HCV infection and depression among U.S. adults using a nationally representative sample. Methods: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2020. The study included 8,443 participants aged 18 years and above who completed the depression screening questionnaire and underwent HCV testing. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), and HCV infection was determined by the presence of HCV RNA. Multivariable logistic regression was used to examine the association between HCV infection and depression while adjusting for potential confounders. Results: In the bivariate analysis, HCV-positive individuals had a significantly higher prevalence of depression compared to HCV-negative individuals. However, after adjusting for potential confounders in the multivariable analysis, the association between HCV status and depression was no longer statistically significant. Age, marital status, and smoking status emerged as significant predictors of depression in the adjusted model. Conclusion: This study found a significant association between HCV infection and depression in the bivariate analysis, but this relationship was attenuated after adjusting for potential confounders. The findings highlight the importance of considering multiple risk factors when assessing the mental health of individuals with HCV infection and underscore the need for targeted interventions to prevent and treat depression in high-risk groups.21 0Item Restricted Quantitative Detection of Hepatitis C Virus RNA in Dried Blood Spots(The University of Manchester, 2024-05-16) Ismaeel, Loui; Klapper, PaulAn estimated fifty-eight million people have chronic hepatitis C virus (HCV) infection, with about 1.5 million new infections occurring each year. A sizeable proportion of these new infections occur among injecting drug users. Dried blood spots (DBS) have revolutionised HCV diagnosis in this difficult to reach population and have further advantages when used in healthcare resource-poor regions of the world. Diagnosis of infection may be made serologically but confirmation of chronic infection necessitates the detection of HCV RNA and response to therapy must be monitored by quantitation of HCV RNA in blood (‘viral load’). A current limitation of the use of DBS is that quantitation of HCV RNA is not possible from standard DBS samples as test blood volume cannot be accurately measured. In the present work a volumetric microfluidic device (HemaXis™ DB 10) was evaluated for preparation of DBS samples to allow quantitation of HCV RNA from the DBS. The HemaXis device was used in conjunction with a custom-made Perkin Elmer 226 paper collection card. Cross contamination between samples was avoided using 10mm diameter perforations to allow individual processing of samples. Extraction of RNA used a modified Qiagen extraction kit and the internally controlled (MS2) HCV RNA quantitative PCR had a limit of detection in DBS specimens of 8.46 IU/mL comparing well with the limit of detection of the reference assay (Cobas® AmpliPrep TaqMan® HCV Test, v2.0; Roche Diagnostics) in EDTA plasma which is 8.5 IU/mL when using a sample size of 500µL. Previously tested HCV RNA positive (n = 125) and HCV RNA and HCV antibody negative (n = 138) serum and plasma samples were used to prepare mock DBS samples by mixing with packed cells from an HCV RNA and HCV antibody negative donor blood. The HemaXis device was used to deliver 10µL samples for each spot. QPCR of mock DBS samples prepared from the 125 HCV RNA positive whole blood samples gave 104 positive HCV RNA results from the DBS. This gave a qualitative test sensitivity of 85.6% and specificity of 100%. A Bland-Altman plot of the differences between the two tests showed that on average the DBS system determines a log 3.37 (2,344 IU/mL) lower value than testing of plasma. The reduction was independent of viral load. Review of the results of internal control testing suggested many samples had evidence of inhibition suggestive of sample deterioration between the time of initial testing of whole blood specimens and the preparation of the mock DBS specimens. Contemporaneous testing of DBS and plasma would be needed to confirm this suggestion. The DBS prepared using the HemaXis were also evaluated for use in genotyping and sequencing of the NS5B and core regions of HCV. Determination of genotype with discrimination of subtypes and of mixed infections was shown to be possible from the DBS samples. The consistent (albeit lower) viral load determination made when using HemaXis prepared DBS shows that this technology has promise as a method for quantitation of HCV RNA load from DBS. Together with the proven ability to genotype HCV using the same sample, the utility of DBS in the diagnosis and management of HCV infection will be further extended.17 0Item Restricted Leveraging bulk RNA-seq data to explore the impact of cirrhosis and PNPLA3 on liver gene expression in HCV-infected patients(University of Oxford, 2023-10-02) Aljawini, Nora; Ansari, AzimHepatitis C virus (HCV) is a hepatotropic RNA virus that is associated with significant morbidity and mortality. Despite interventions to prevent transmission, HCV infection continues to result in 400,000 annual deaths worldwide and is a primary indication of liver transplantation. While a quarter of patients with acute infection clear the virus spontaneously, the remaining three-quarters develop chronic infection and cirrhosis. Alongside HCV, the primary aetiologies of cirrhosis include non-alcoholic fatty liver disease (NAFLD), and alcoholic fatty liver disease (ALD). The risk of cirrhosis is influenced by the complex interplay between host, viral and environmental factors. A single nucleotide polymorphism (SNP), rs738409, is the strongest genetic risk factor for ARLD- and NAFLD-related cirrhosis. To date, no study has been conducted that investigates the impact of cirrhosis on liver gene expression during chronic HCV. To address this knowledge gap, we leveraged bulk RNA-seq data from a cohort of 196 HCV-infected patients enrolled in the BOSON clinical trial to investigate the effect of cirrhosis and PNPLA3 on liver gene expression. Our analyses showed that thousands of genes are upregulated and downregulated by cirrhosis, many of which are linked to extracellular matrix remodelling processes (such as MMP7), inflammation (CCL2) and other cirrhosis-related pathways, but also several potentially novel pathways as well. PNPLA3 was found to be downregulated during cirrhosis, as previously reported in the literature. We demonstrated that rs738409 is linked with several expression patterns and pathways, namely mitochondrial transcripts (e.g. MT-TC, MT-TN) and apoptosis-related signaling genes (e.g. BAX). These insights may generate novel hypotheses to test downstream for additional targets in drug development for liver cirrhosis. Overall, our analyses demonstrate how gene expression data combined with robust statistical methodology holds the potential to serve basis for elucidating the underlying mechanisms of cirrhosis.16 0