Potential Anti-Fibrotic Effect of Direct Acting Antiviral Drugs on CCl4 Induced Hepatic Fibrosis in Rats

Background: Hepatic fibrosis is a hall mark of chronic liver diseases such as chronic HCV. Direct acting antiviral (DAA) regimens such as Sofosbuvir (SOF) and daclatasvir (DAC) have been found to be associated with decreased fibrotic markers in HCV patients. It is not clear however the reported antifibrotic effect is antiviral dependent or not. Aim: This study investigated the effect of SOF and DAC in hepatic fibrosis induced by CCl4 in rats. Method: Hepatic fibrosis was induced by (0.5 ml/kg) CCl4 IP twice a week for six weeks. SOF (20 mg/kg/d) and DAC (30 mg/kg/d) were added in the last four weeks of treatments. Liver functions, fibrotic markers such as Hyaluronic acid and metalloproteinase-9 were detected using immunoassay. Liver tissues were examined by different stains. Results: SOF and DAC induced marked inhibitions in fibrotic markers expression significantly (P≤0.001). Moreover, the drugs protected liver tissues from progressed fibrosis. Conclusion: SOF/DAC antifibrotic effect is independent on its antiviral activity

Effect of genetic polymorphisms on the development of secondary failure to sulfonylurea in Egyptian patients with type 2 diabetes

Objective: This study investigated the possibility that genetic factors, such as polymorphism of K inward rectifier subunit (Kir6.2), E23K, and Arg 972 polymorphism of insulin receptor substrate-1 (IRS-1), may predispose patients to sulfonylurea failure. Methods: A total of 100 unrelated Egyptian patients with type 2 diabetes were recruited. They were divided into two equal groups: group I consisted of patients with secondary failure to sulfonylurea (hemoglobin A 1c  ≥ 8% despite sulfonylurea therapy) while group II consisted of patients whose condition was controlled with oral therapy. Results: Of all the patients, 45% and 14% were carriers of the K allele and Arg 972 variants respectively. The frequency of the K allele was 34% among patients with diabetes that was controlled with oral therapy and 56% among patients with secondary failure to sulfonylurea. The frequency of the Arg 972 IRS-1 variant was 6% among patients with diabetes controlled with oral therapy and 22% among patients with secondary failure. Conclusion: The E23K variant of the Kir6.2 gene and Arg 972 IRS-1 variants are associated with increased risk for secondary failure to sulfonylurea