Safety and Efficacy of Sofosbuvir Based Regimen on Patients With End Stage Renal Disease—A Single Centre Experience (original) (raw)
Related papers
Hepatitis Monthly, 2016
Background: MicroRNAs (miRNAs) have been repeatedly shown to play important roles in liver pathologies, including hepatitis, liver cirrhosis, and liver cancer. Egypt has the highest hepatitis C virus (HCV) infection rate worldwide, predominantly involving genotype-4. Objectives: In this study, we attempted to characterize the miRNA profile of the poorly studied genotype 4 of HCV in chronically infected Egyptian patients to obtain a better understanding of the disease and its complications and help in the design of better management protocols. Patients and Methods: We analyzed the expression levels of a selected panel of 94 miRNAs in fresh liver biopsies collected from 50 Egyptian patients diagnosed with chronic HCV infection using quantitative real-time polymerase chain reaction (PCR) assay. Nonparametric tests were used to analyze the expression level of each miRNA and association with the clinicopathological features of enrolled patients in this study. Results: Our results revealed differential expression levels of the analyzed miRNAs compared to the normal controls. Twenty-seven miRNAs (including miR-105, miR-147, miR-149-3p, and miR-196b) showed up-regulation, while 17 miRNAs (including miR-21, miR-122, miR-199a-3p, and miR-223) showed down-regulation. An inverse correlation was observed between levels of miR-95, miR-130a, and miR-142-5p with the blood albumin level. Increased expression levels of seven miRNAs (miR-29c, miR-30c, miR-126, miR-145, miR-199a, miR-199a-3p, and miR-222) were observed with severe chronic hepatic inflammation. Several deregulated miRNAs found in this study have been previously linked to chronic liver inflammation and the risk of hepatocellular carcinoma (HCC) development. Conclusions: The identified expression profiles of some examined miRNAs might offer important points to consider for the treatment of naive patients and the management of chronically infected HCV patients in Egypt and around the world.
MicroRNAs: Role in hepatitis C virus pathogenesis
Genes & Diseases, 2015
Hepatitis C virus (HCV) is a global health burden with an estimated 170e200 million peoples chronically infected worldwide. HCV infection remains as an independent risk factor for chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and a major reason for liver transplantation. Discovery of direct acting antiviral (DAA) drugs have shown promising results with more than 90% success rate in clearing the HCV RNA in patients, although long-term consequences remain to be evaluated. microRNAs (miRNAs) are important players in establishment of HCV infection and target crucial host cellular factors needed for productive HCV replication and augmented cell growth. Altered expression of miRNAs is involved in the pathogenesis associated with HCV infection by controlling signaling pathways such as immune response, proliferation and apoptosis. miRNA is emerging as a means of communication between various cell types inside the liver. There is likely possibility of developing circulating miRNAs as biomarkers of disease progression and can also serve as diagnostic tool with potential of early therapeutic intervention in HCV associated end stage liver disease. This review focuses on recent studies highlighting the contribution of miRNAs in HCV life cycle and their coordinated regulation in HCV mediated liver disease progression.
F1000 - Post-publication peer review of the biomedical literature, 2014
Hepatitis C virus (HCV)-induced chronic liver disease is one of the leading causes of hepatocellular carcinoma (HCC). The molecular events leading to HCC following chronic HCV infection remain poorly defined. MicroRNAs (miRNAs) have been implicated in the control of many biological processes, and their deregulation is associated with different viral infections. In this study, we observed that HCV infection of hepatocytes transcriptionally downregulates miR-181c expression by modulating CCAAT/enhancer binding protein  (C/EBP-). Reduced expression of the pri-miR-181c transcript was noted following HCV infection. In silico prediction suggests that homeobox A1 (HOXA1) is a direct target of miR-181c. HOXA1 is a member of the homeodomain-containing transcription factor family and possesses pivotal roles in normal growth, development, and differentiation of mammalian tissues. Our results demonstrated that HOXA1 expression is enhanced in HCV-infected hepatocytes. Exogenous expression of the miR-181c mimic inhibits HOXA1 and its downstream molecules STAT3 and STAT5, which are involved in cell growth regulation. Interestingly, overexpression of miR-181c inhibited HCV replication by direct binding with E1 and NS5A sequences. Furthermore, accumulation of HCV genotype 2a RNA with miR-181c was observed in an RNA-induced silencing complex in Huh7.5 cells. Our results provide new mechanistic insights into the role of miR-181c in HCV-hepatocyte interactions, and miR-181c may act as a target for therapeutic intervention.
Hepatitis C virus infection, microRNA and liver disease progression
World Journal of Hepatology, 2013
Hepatitis C virus (HCV) is a global health problem with an estimated 170-200 million peoples (approximately 3% of world population) are chronically infected worldwide and new infections are predicted to be on rise in coming years. HCV infection remains categorized as a major risk factor for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. There has been considerable improvement in our understanding of virus life cycle since, the discovery of HCV two-decades ago. MicroRNAs (miRNAs) are important players in establishment of HCV infection and their propagation in infected hepatocytes. They target crucial host cellular factors needed for productive HCV replication and augmented cell growth. Very first anti-miRNA oligonucleotides, miravirsen has been tested in clinical trial and shown promising results as therapeutic agent in treatment against chronic HCV infection. Deregulated expression of miRNAs has been linked to the pathogenesis associated with HCV infection by controlling signaling pathways such as, proliferation, apoptosis and migration. Circulating miRNAs emerging as growing field in identification of biomarkers in disease progression and their potential as a means of communication between cells inside the liver is an exciting area of research in future. This review focuses on recent studies enforcing the contribution of miRNAs in HCV life cycle and coordinated regulation in HCV mediated liver disease progression.
MicroRNAs and hepatitis C virus: Toward the end of miR-122 supremacy
Virology Journal, 2012
The most common etiologic agents causing chronic hepatitis are hepatitis C and B viruses (HCV and HBV, respectively). Chronic infection caused by HCV is considered one of the major causative agents of liver cirrhosis and hepatocellular carcinoma worldwide. In combination with the increasing rate of new HCV infections, the lack of a current vaccine and/or an effective treatment for this virus continues to be a major public health challenge. The development of new treatments requires a better understanding of the virus and its interaction with the different components of the host cell. MicroRNAs (miRNAs) are small non-coding RNAs functioning as negative regulators of gene expression and represent an interesting lead to study HCV infection and to identify new therapeutic targets. Until now, microRNA-122 (miR-122) and its implication in HCV infection have been the focus of different published studies and reviews. Here we will review recent advances in the relationship between HCV infect...
2021
BackgroundEarly detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this poorly diagnosed widely-spread disease. Dysregulation in microRNA (miRNAs) expression is associated with HCC progression. MethodsThe objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE- miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424 and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV and 72 HCV-associated HCC patients using real time PCR (qPCR).ResultsThere was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 exp...
MicroRNA in HCV infection and liver cancer
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2011
In the more than two-decades since hepatitis C virus (HCV) was identified, there has been considerable improvement in our understanding of virus life cycle due largely to the development of in vitro culture systems for virus replication. Still challenges remain: HCV infection is a major risk factor for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide; yet mechanistic details of HCV infection-associated hepatocarcinogenesis remain incompletely understood. A protective vaccine is not yet available, and current therapeutic options result in sustained virus clearance only in a subset of patients. Recent interest has focused on small non-protein coding RNAs, microRNAs (miRNAs), the dependence of virus replication on miRNAs, and miRNA-regulated genes in liver cancer. Functional analysis of the miRNA-targeted genes in liver cancer has advanced our understanding of the "oncomiRs" and their role in hepatocarcinogenesis. This review focuses on the dependence of HCV replication on miRNA and role of miRNA-targeted tumor suppressor genes as molecular markers of and possible targets for developing oncomiR-targeted therapy of chronic hepatitis and HCC. This article is part of a Special Issue entitled: MicroRNAs in viral gene regulation.
Increased hepatic expression of miRNA-122 in patients infected with HCV genotype 3
Medical Microbiology and Immunology
Hepatitis C virus (HCV) infection affects approximately 3 % of the world population. HCV targets hepatic tissue, and most infected patients develop a chronic infection. Currently, studies have demonstrated an association between HCV-RNA replication and miR-122, the most abundant microRNA in the liver. Our aim was to evaluate liver and serum expression of miR-122 in patients infected with HCV genotypes 1 and 3, and to identify possible associations between miR-122 expression and lipid profiles, HCV viral load, apolipoproteins and liver enzymes. MicroRNAs were isolated from blood and liver tissue, and miR-122 expression was quantified by real-time PCR. HCV viral load was quantified by real-time PCR and HCV genotype, and serum biomarkers were obtained from medical report. The levels of miR-122 were higher in liver than those in blood from individuals infected with HCV genotypes 1 and 3 (p < 0.0001). The tissue levels of miR-122 were higher in subjects infected with HCV genotype 3 (6...
Cancers, 2021
Hepatitis C virus (HCV) genome encodes for one long polyprotein that is processed by cellular and viral proteases to generate 10 polypeptides. The viral structural proteins include the core protein, and the envelope glycoproteins E1 and E2, present at the surface of HCV particles. Non-structural (NS) proteins consist of NS1, NS2, NS3, NS4A, NS4B, NS5a, and NS5b and have a variable function in HCV RNA replication and particle assembly. Recent findings evidenced the capacity of HCV virus to modulate host cell factors to create a favorable environment for replication. Indeed, increasing evidence has indicated that the presence of HCV is significantly associated with aberrant miRNA expression in host cells, and HCV structural and non-structural proteins may be responsible for these alterations. In this review, we summarize the recent findings on the role of HCV structural and non-structural proteins in the modulation of host cell miRNAs, with a focus on the molecular mechanisms responsi...