Abstract

There are estimated to be more than a hundred million hepatitis C virus (HCV) carriers worldwide. About 30% of carriers develop serious liver diseases, such as liver cirrhosis and hepatocellular carcinoma. HCV Genotype 1 is the most common genotype worldwide and the most difficult to treat with interferon-based therapy. Therapy for patients with chronic HCV infection is complicated by poor tolerability and inadequate rates of sustained virological response (SVR). Although the addition of a protease inhibitor in combination with peg-interferon alpha plus ribavirin improved SVR rates and shortened the treatment period, many patients could not tolerate this therapy because of advanced age and clinical conditions such as anemia and low platelet count. Interferon-free therapies that combine two or more direct-acting antiviral (DAA) agents can improve both efficacy and tolerability. Phase III trials of daclatasvir plus asunaprevir, ombitasvir plus parataprevir/r, and sofosbuvir plus ledipasvir all showed high overall SVR rates with few adverse events. However, development of antiviral resistance is a concern with DAA therapies, and it is important to avoid treating patients with existing NS5A Y93H mutations with daclatasvir plus asunaprevir or ombitasvir plus parataprevir/r therapy to prevent viral breakthrough. Fortunately, sofosbuvir plus ledipasvir therapy seems to be less affected by NS5A Y93H variants. An important goal of HCV therapy is to expand treatment to all patients. The current study aims to show the efficacy and safety of these therapies both in clinical trial and real world settings based on our own clinical experiences.