Transcriptional Analysis of TP53 Gene in Chronic Hepatitis C Patients Treated with Sofosbuvir, Daclatasvir, Pegylated Interferon, and Ribavirin

Abstract

Hepatitis C virus (HCV) is a major public health problem that affects more than 170 million people globally. HCV is a principal cause of hepatocellular carcinoma (HCC) around the globe due to the high frequency of hepatitis C infection, and the high rate of HCC is seen in patients with HCV cirrhosis. TP53 is considered as a frequently altered gene in all cancer types, and it carries an interferon response element in its promoter region. In addition to that, the TP53 gene also interacts with different HCV proteins. HCV proteins especially NS3 protein and core protein induce the mutations in the TP53 gene that lower the expression of this gene in HCV patients and leads to HCC development. In this study, we examined the transcriptional analysis of the TP53 gene in HCV-infected patients administered with different combinations of antiviral therapies including sofosbuvir + daclatasvir, sofosbuvir + ribavirin, and pegylated interferon + ribavirin. This study included 107 subjects; 15 treated with sofosbuvir + daclatasvir, 58 treated with sofosbuvir + ribavirin, 11 treated with interferon + ribavirin, 8 untreated, 10 HCC patients, and 5 were healthy controls. Total RNA was extracted from the PMBCs of HCV infected patients and reverse transcribed into cDNA using a gene specific reverse primer. The expression level of TP53 mRNA was analyzed using quantitative PCR. The expression of TP53 mRNA was notably upregulated in rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR) groups as compared to non-responders and naïve groups. The expression of TP53 mRNA was seen high in HCC as compared to control groups. Additionally, it has been demonstrated that sofosbuvir + daclatasvir treatment stimulates significant elevation in TP53 gene expression as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. This study indicates that the TP53 gene expression is highly upregulated in RVR, EVR, and SVR groups as compared to control groups. Moreover, sofosbuvir + daclatasvir therapy induces significant rise in TP53 mRNA expression levels as compared to (sofosbuvir + ribavirin) and (IFN + ribavirin) treatment. According to these results, it can be concluded that sofosbuvir + daclatasvir plays a significant role in preventing HCV patients from developing severe liver complications as compared to other administered therapies. This study is novel as no such type of study has been conducted previously on the expression of TP53 in local HCV-infected population treated with different combinations of therapies. This study is helpful for the development of new therapeutic strategies and for improving existing therapies.