THE POSSIBLE HISTOLOGICAL EFFECTS OF DACLATASVIR ON LIVER CELLS OF THE PREGNANT MICE

Abstract

Introduction: HCV infection is a worldwide health problem. Egypt is one of the highest prevalence in adults. The prevalence of infection in pregnancy is between 1% and 8%. Treatment during pregnancy has been associated with many problems. Unfortunately, till now there is no approval for an antiviral drug to be used in pregnancy. A new group of antiviral agents has emerged known as directing acting antivirals (DAAs). Daclatasvir (DCV) is one of the second generation DAAs that has pangenotypic activity. Aim of the work: was to assess the possible histological effects of daclatasvir on the liver cells of the pregnant mice.Materials and Methods: Forty adult pregnant female mice were divided into two main groups; Group I (control group), included 10 mice which received distilled water. Group II (DCV group): included 30 mice subdivided into three equal groups: group IIa (DCV 12.5 mg/kg), group IIb (DCV 25 mg/kg) and group IIc (DCV 50 mg/kg body weight). They received the drug orally from GD6 to GD15. The pregnant mice were sacrificed (at GD 18-19) under anesthesia and after taking blood samples for biochemical analysis. Liver specimens were processed for histological and morphometric analysis.Results: Maternal toxicity with increased maternal mortalities was observed. Common hepatocellular changes in the three experimental groups showing; disturbed hepatic architecture, hypereosinophilic foci with indistinct boundaries, nuclear alterations, cellular vacuolation and prominent Von-kupffer cells. The presence of basophilic foci was prominent in GIIc. Increased collagen deposition and high levels of liver enzymes were mostly prominent in GIIa more than GIIc and GIIb respectively. These findings were concomitant with idiosyncratic drug induced liver injury (DILI) with pregnancy.In conclusion, DCV administration during pregnancy has a dose-dependent potential risk of DILI. Future studies are recommended to improve maternal outcome.