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Title: Expression Profile of Different Circulatory Micro-Rnas in Hcv Cirrhotic Patients from Khyber Pukhtunkhwa, Pakistan.
Authors: Amin Ullah
Keywords: Biological & Medical Sciences
Issue Date: 2020
Publisher: University of Peshawar, Peshawar.
Abstract: Hepatitis C virus (HCV) is one of the main causes of liver diseases that leads to cirrhosis and hepatocellular carcinoma. There are about 170 million individuals who are chronically infected which HCV around the world. HCV is an enveloped single stranded RNA virus with a genome size of 9.6 kb. HCV replication is error-prone which leads to its highly heterogeneous nature. Based on this heterogeneity, the HCV has (1-6) genotypes and approximately 70 subtypes with diverse prevalence rate and geographic distribution. A total of 267 HCV cirrhotic patients were selected for this study, including 159 males and 108 females. The average age with standard deviation (SD) of the patients was 49.62±12.65 years respectively. All the cirrhotic patients were divided into three groups on the basis of severity/liver damage; gross, moderate and mild cirrhosis with the frequencies of 147, 87 and 33 respectively. The average mean and standard deviation of the ALT was 121.46±29.23 IU/L. Alpha fetoprotein (AFP) level was reported <40 ng/ml in 57%, 41 to 150 ng/ml in 33% and >150 ng/ml in 10% of the HCV cirrhotic patients. Variable blood pressure (BP) was observed in these patients, high in 70, low in 109 and normal in 88 patients. The ascites accumulation was recorded higher in 157 patients. The level of albumin was abnormal in 174 patients. Samples of 47 HCV cirrhotic patients were subjected to 5ʹ UTR sequencing and the data was analyzed by MEGA 7.0 software. The phylogenetic analysis revealed that different isolates were clustered with reference genotypes sequence including, 3a (59%) and 2(6%) of each genotype 1, 2 and 4. Phylogenetic analysis of the 5ʹ UTR sequences showed homology with the reported genotypes from Afghanistan, Bolivia, India, Indonesia, Japan, Denmark, New Zealand and US. The genotype of HCV in these cirrhotic patients were 1a in 6%, 1b in 1.1%, 2a in 11%, 3a in 48.9%, 3b in 10.5%, mixed in 4.1% and untyped 18.7% of the total infected patients. Genotype 3a was predominant in these patients. All the patients were treated with different antiviral drugs for 12 and 24 weeks according to their observed genotypes. Therefore, a combination of antiviral drugs i.e. sofosubuvir (SOF) + ribavirin (RBV) showed Sustained Virological Response (SVR) (89%), sofosbuvir (SOF) + daclatasvir (DCV) (85%) and SOF + DCV with RBV (83%) xv in the HCV cirrhotic patients. Genotype 3a disclosed significant SVR to SOF+RBV (92.68%), SOF+DCV (85%) and SOF plus DCV with RBV (88.23%) as compared to the other genotypes. Based on the SVR results, the efficacy of sofosbuvir + ribavirin is significant as compared to the other two combinations of drugs for HCV cirrhotic patients. The expression profile of microRNAs showed that miRNA has a complementary role in the development of end stage liver disease. The expression profile of miR-122 significantly up regulated with (p <0.0019), miR-192 (p <0.0017) and miR-29a (p <0.0001) as compared to healthy control. The member of Let-7b (p <0.0001) and Let7c (p <0.0001) family were significantly up regulated in the HCV cirrhotic patients. There was no significant difference observed in the expression of miR-21a of HCV cirrhotic patient as compared to control group. Next Generation Sequencing (NGS) was performed for 16 HCV cirrhotic samples (8 moderate, 8 gross) with 8 healthy control on the basis of ALT level of HCV patients. After the analysis some of the specific up regulated (Let 7b-5p, let-7i-5p, miR-101-3p, miR-122-5p, hsa-miR-103a-3p, miR-126-5p, miR-126-3p, miR-16-5p, miR-142-3p, miR-142-3p, miR-192-5p, miR-21-5p, miR-223-3p, miR-29a-3p, miR-451a, hsa-miR486-5p, miR-92a-3p, miR-142-5p, miR-148a-3p) and down regulated (miR-146a-5p, miR-320a, let-7c-5p, let-7f-5p, let-7g-5p, let-7e-5p, miR-150-5p, miR-423-5p, let-7a5p) miRNAs were reported in these HCV cirrhotic patients.
Gov't Doc #: 20215
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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