Evaluation of Ledipasvir plus Sofosbuvir for treatment of compensated and decompensated HCV cirrhotic patients

ABSTRACT

Background:unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct acting antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir, simeprevir and fixed combination medicines containing ledipasvir plus sofosbuvir and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the "cure HCV" goal has become a reality. The aim of this study was to assess of ledipasvir plus sofosbuvir as treatment of HCV infection in patients with advanced liver disease including cirrhotic patients with child B and C. Patients and methods:in this prospective study, seventy five HCV PCR positive patients were classified into three groups according to child score. Each group included twenty five patients. All patients received ledipasvir plus sofosbuvir for six months. For all patients thorough medical history, clinical examination, kidney function tests, liver function tests, complete blood count, pelvi-abdominal ultrasound, HCVantibodies, hepatitis C viral RNA, quantitative, HbsAg, alpha fetoprotein as baseline screening. HCV PCR done for all patients at end of treatment and three months later to detect sustained virological response (SVR12). Patients with combined HCV and HBV infection, hepatic or extrahepatic malignancies and late child C were excluded. Results: showed that no statistical significant difference were detected in patients of group A as regard liver function tests before and after treatment and SVR12 achieved by 96%. Patients of group B showed significant statistical difference as regard liver function tests before and after treatment with SVR12 achieved by 88%. In patients of group C there were significant statistical difference in liver function tests with SVR12 achieved by 80%. Also there were clinical improvement in patients of group B and C after end of treatment. Conclusion:it could be concluded that there will be a dramatic improvement in HCV therapy followed the introduction of oral medicines that directly inhibiting the replication cycle of HCV. The combination pill contains a fixed-dose of ledipasvir 90 mg and sofosbuvir 400 mg, two direct-acting antiviral agents against HCV. Ledipasvir is an inhibitor of the NS5A protein, which is required for HCV replication. Sofosbuvir inhibits the HCV NS5B RNA-dependent RNA polymerase, which is also required for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form a pharmacologically active triphosphate that can incorporate into the HCV RNA. Ledipasvir plus sofosbuvir can be used safely in treatment of compensated and decompensated post hepatitis C liver cirrhosis. SVR12 can be achieved by 96% in patients with early cirrhosis (child A), 88% in patients with child B cirrhosis and 80% in patients with child C with subsequent improvement in liver functions