New markers for diagnosis and management of chronic hepatitis C virus infection

Over 130 million individuals are chronically infected with hepatitis C virus (HCV) worldwide [1]. In spite of the existence of antiviral treatments based on dual or triple therapies with substantial cure rates that vary according to the viral genotype, chronic HCV infection remains the first cause of chronic hepatitis and cirrhosis in Europe and has become the first indication for liver transplantation in industrialized countries [2]. The complications of HCV infection represent the 10 th most frequent cause of death of infectious origin worldwide, with approximately 350,000 deaths per year and more than 7,500 in the United States in 2004 [3]. Chronic hepatitis C remains a global health problem, with considerable geographic variation of its prevalence. A high prevalence of chronic HCV infection has been reported in African and Eastern Mediterranean countries, with a prevalence of 14.7% in the general population of Egypt, whereas the HCV prevalence varies from 0.4-0.8% in Sweden, Germany, the Netherlands and France to over 1.9% in the Unites States, and over 5% in some communities in Italy [4-6]. Because chronic hepatitis C is often asymptomatic until advanced liver disease stages develop, up to approximately 60% of infected patients are unaware of their infection and related liver disease [7]. A late detection and diagnosis of HCV infection has important clinical implications, because advanced fibrosis and cirrhosis have been identified as independent pretreatment predictors of failure of treatments based on interferon-α, as well as key factors of morbidity and mortality [8]. Early diagnosis and treatment of HCV infection can reduce the risk of development of long-term complications and prevent further transmission. Virology tools developed over the past 20 years are routinely used to diagnose and monitor chronic HCV infection. Classical assays include molecular tools used to detect and quantify HCV RNA, and techniques that determine the HCV sequence in order to determine the genotype and the subtype and eventually identify clinically relevant amino acid substitutions associated with resistance to direct acting antivirals (DAA). New assays capable of detecting and quantifying HCV core antigen are now approved in Europe and are available for research use only in the United States. Moreover, recent advances include alternatives approaches that require whole blood or oral fluid samples and will be used to extend HCV screening and improve access to care in regions without molecular biology laboratories. A variety of biological makers are useful for the virological diagnosis and monitoring of chronic HCV infection, as well as screening of hepatitis C infection. Virological markers [total anti-HCV antibodies (Ab), core antigen titer, HCV RNA level and viral genotype], biochemical markers (ALT activity) and histological markers (hepatic fibrosis stage and necroinflamatory activity grade) are currently used in clinical practice to diagnose and monitor chronic hepatitis C. Among them, HCV RNA quantification before treatment is important for decision making. All treatment-naive patients with compensated liver disease and detectable HCV RNA are candidates for therapy. New molecular methods for quantifying HCV RNA in blood are based on real-time PCR (polymerase chain reaction) or TMA (transcription-mediated amplification) assays. These assays are fully or partly automated. With a broader range of linear quantification, a lower limit of detection (LLOD) in the order of 10-15 IU/mL, and an identical LLOD and lower limit of quantification (LLOQ) for the most recent assays,