Protein kinase expression as a predictive factor for interferon response in chronic hepatitis C patients

Abstract

Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Currently, combined pegylated interferon and ribavirin therapy are the standard treatment. The biological activity of interferon (IFN) is mediated by the induction of intracellular antiviral proteins, such as 2′–5′ oligoadenylate synthetase, and dsRNA-activated protein kinase. IFN-inducible double-stranded RNA-activated protein kinase (PKR) is thought to play a key antiviral role against HCV. Some studies observed that PKR expression was higher in sustained viral responders compared with the non-responders. The PKR is considered as antiviral toward HCV and responsible for IFN’s effect against HCV while others have showed that, there were kinetic results indicate that HCV infection is not altered by reduced levels of PKR, indicating that HCV is resistant to the translational inhibitory effects of the phosphorylated forms of PKR. This study was conducted on 50 consecutive patients with chronic HCV infection (CHC) and 20 healthy controls. All the patients were subjected to clinical and laboratory assessment, abdominal ultrasound, and liver biopsy. Determination of PKR gene quantity by using a real time PCR was done at the baseline and at the end of treatment for all patients and controls. Pre-treatment levels of protein kinase gene were significantly higher in responders in comparison with non-responders (P < 0.001). It was found that 97.06% of patients who were responding to treatment had the expression of protein kinase gene greater than 26 cycle threshold.

Novel Mechanisms Controlling the Expression of the Antidiabetic Hepatokine Fibroblast Growth Factor 21

“…RNAs, with a minimum of 33 bp, bind to its dsRNA-binding domain (172,173). Due to the strict requirement of dsRNA activation, PKR activity in the liver is often correlated with viral infections such as hepatitis C (174)(175)(176)(177). It is no surprise then that hepatitis C infection increases FGF21 mRNA abundance in the liver, presumably through PKR-mediated phosphorylation of eIF2α and enhanced transactivation of ATF4 to the FGF21 promoter (178).…”