الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus (HCV) infection is a major public health problem in Egypt. Hepatocellular carcinoma (HCC) is a major malignancy worldwide, being the second most frequent cause of cancer death in men and the sixth in women, and hepato-carcinogenesis is closely associated with HCV infection. More than 90% of the HCC cases in Egypt were attributable to HCV infection. In the last few years, a dramatic progress in the treatment of HCV had been achieved with direct acting antiviral (DAAs) with outstanding results reaching more than 90% sustained virological response (SVR). This remarkable achievement represents a major breakthrough in hepatology. Many recent studies and reports have implications on the effect of DAAs on HCC occurrence and recurrence after successful treatment. MiRNAs play a remarkable role in regulating gene expression during oncogenic process in virally infected patients. MicroRNAs (miRNAs) negatively regulate gene expression and may act as oncogenes, or tumor suppressors, or play dual roles in hepatocarcinogenesis regulating cell cycle, cell proliferatic migaraion, and apoptosis. The aim of the present work is to Study the occurrence of HCC in HCV positive patients after achieving SVR by DAAs, and to investigate the role of miR 181a in this domain. I- The present work was performed on 90 patients, 58 males (64%) and 32 ’females (36%), with age ranged from 47 to 67 years. The patients were selected from Oncology Center Mansoura University (OCMU) and specialized medical hospital Mansoura university. The 90 patients will be divided into 3 groups: group 1: 30 HCV-related HCC patients received DAAs previously and in SVR within 2 years of HCC diagnosis. group 2: 30 HCV-related HCC patients without a previous history of exposure to DAAs. group 3: 30 patients with chronic HCV (CLD= chronic liver diseases) treated by DAAs without developing HCC within 2 years of treatment and in SVR. in addition to a control group of 10 normal persons with matched age and sex. All patients gave informed consent to their participation in this study, and the local ethics committee gave prior approval to the study. Diagnosis of HCC: All HCC patients were on top of HCV cirrhosis and HCC diagnosis was made upon the presence of hepatic focal lesions diagnosed by abdominal ultrasound and confirmed by computed tomograph (CT) and/or magnetic resonance imaging according to European Association of the Study of the Liver (EASL) guidelines.In addition to the routine laboratory investigations, serology for HCV, and AFP.HCV RNA by PCR, Plasma samples were isolated within 1 h after receiving whole blood and then immediately stored at-80 oc for subsequent extraction. miR 181a quantification was done by real time PCR and the. The relative mmir exv.reison level was calculated.Statistical analysis and data interpretati was done using IBM SPSS Corp. Released 2013 Laboratory data analysis among the studied group, revealed that a significant increase in HCC patient groups whatever exposed to DAA or not in comparison to HCV CLD patients with SVR as regard (ALT, AST, Total bilirubin, INR and AFP, While albumin and Hb levels noticed to be significantly decreased HCC patient groups in comparison to HCV CLD patients with SVR.Also the fibrosis stage by fibroscan among the studied group, showed significant increase in HCC patient groups whatever exposed to DAA or not in comparison to HCV CLD patients with SVR.while no significant differences in tumour size was detected between the 2 HCC groups. Up-regulation of miR-l8la in HBV-related HCC cell lines and HBV could induce miR-18la expression by enhancing its promoter activity. It is therefore possible that miR-18la might contribute to the carcinogenesis ofHBV-related HCC In the present work ,significant upregulation of micR-181a in the sera was detected in the 3 groups:Post DAA HCV related CLD patients in SVR, and also in both HCV related HCC patients whether exposed or not to DAA in comparison to control group.This upregulation is observed more in CLD group than in both bee groups, however this difference is not statisticaly significant. indicating that this upregulation is not related to DAA treatment, but most probably related to liver pathology either post HCV CLD And/or post HCV HCC patients either treated or not by DAA. This upregulation is not related to liver function tests, CBC, INR, fibrosis stage nor survival in CLD patients treated by DAA and in SVR nor in HCC post HCV patients in SVR after DAA.However in the group of post HCV HCC patients not exposed to DAA and not in SVR this upregulalion is positively and AFP level and negatively correlated to haematological parameters:hafmogin, pJJtelets count and INR, but not surv Correlation analysis between Plasma micRNA 181a and serum AFP in the 60 patients with HCC a significant positive correlation was detected between AFP and micRNA 181a.Although upregulation was detected in HCV CLD patients, serum micRNA. 181a may serve as a minimally invasive biomarkers for diagnosis of post HCV HCC however a higher number of cases is needed to reach a solid conclusion. Although there is no significant differences in survival between the 2 HCC pateints groups, it was noticed that in both groups, low levels ofmiR-181a is associated with better survival than in patients with high levels indicating that micRNA 181a level in post HCV HCC patients may have a prognostic value reflecting the overall survival.