1. INTRODUCTION Chronic hepatitis C virus (HCV) infection is a major public health concern. It is estimated that more than 185 million people, around 3% of the world population, are currently living with chronic hepatitis C. About one-third of these individuals will develop cirrhosis and hepatocellular carcinoma (HCC), leading to approximately 350,000 deaths each year. The prevalence of HCV infection in Latin American countries is heterogeneous, as illustrated in table 1. In 2010, the Latin American Association for the Study of the Liver (LAASD) developed its own guidelines for the diagnosis and treatment of HCV. Until 2011, the standard of care for patients with HCV genotype (GT)1 was pegylated interferon (PEG-IFN) plus ribavirin (RBV). The sustained virologic response (SVR) rates were 40-50%. The standard of care for patients with either HCV GT2 or GT3 was PEG-IFN plus RBV for 24 weeks with SVR rates ranging from 69% to 74%.6 At that time, first-in-class protease inhibitors (PIs) [boceprevir (BOC) and telaprevir (TVR)] were the first direct-acting antiviral (DAA) therapies approved for patients with GT1, given in conjunction with both PEG-IFN and RBV for 24-48 weeks, depending on whether the patient had a robust response. The first-generation DAAPIs inhibit the NS3/4A protease, which in turn diminishes viral replication. The SVR rates in pivotal phase 3 studies of treatment-naïve patients with GT1 receiving PEG-IFN plus RBV plus a PI ranged from 63 to 75%. In patients who previously received PEG-IFN plus RBV but did not achieve SVR, superior SVR rates of 75-83% were achieved in relapsers, 52-59% in partial responders, and 29-38% in nonresponders. In 2013, the LAASD reviewed and updated the guidelines to include the first-generation DAAs for treatment and laboratory tests for the diagnosis, monitoring and evaluation of patients with chronic HCV infection. Fortunately, thanks to ongoing research, in vitro systems to culture HCV became available, and these tools have allowed the development of DAAs that are specifically designed to target HCV proteins, particularly the nonstructural proteins. In fact, the efforts have focused on the six nonstructural (NS) proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) that play critical roles in HCV entry, replication, and proliferation, and serve as possible targets for development of the new DAA therapies.
2014-09-11 | 171 visitas | Evalua este artículo 0 valoraciones
Vol. 13 Núm.2. Agosto 2014 Pags. S4-S66 Ann Hepatol 2014; 13(Supl. 2)