The cost-effectiveness of one-time birth cohort testing is comparable to that of current risk-based screening strategies [36]. review, the state of the art about these major topics in the fight against HCV and the future of research in these fields are discussed. 1. Introduction Among infectious diseases, hepatitis C virus (HCV) still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. Chronically infected individuals are estimated to reach 150C170 million worldwide and estimates of incidence, performed in the United States by the Center for disease control and prevention (CDC), reported nearly 30,000 new HCV infections in 2013 [1, 2]. Although HCV contamination is characterized by a global diffusion, its prevalence greatly differs according to geographic area [3, 4]. Central Asia, SBC-110736 Eastern Europe, the Midwest of North Africa region, and Central and Western Sub-Saharan Africa present high HCV prevalence rates, with figures ranging between 3.1% and 5.4%; regions with intermediate prevalence rates are Southern Sub-Saharan Africa, Central Europe, Australia, and Latin America, with values between 1% and 1.4%; low prevalence is found in Oceania (0.1%), Caribbean (0.8%), and Western Europe (0.9%) [3]. After acute contamination, 75% of infected subjects become chronically infected and approximately 20% of this population develops liver cirrhosis during the two decades after contamination if left untreated [5, 6]. However, since in most cases acute contamination was asymptomatic, most HCV infections are clinically silent until the disease reaches a late stage: HCV was estimated to cause 25% of all cases of liver cirrhosis and cancer worldwide and to account for more than 500,000 deaths per year [7]. In recent years, substantial advances have been made to understand HCV biology and to develop a new generation of effective direct-acting antiviral brokers (DAAs) able to cure HCV. However, several challenges hamper an effective control of HCV spread worldwide. In fact, the emergence of drug resistance and the suboptimal activity of these therapies against diverse HCV genotypes have been observed and have been associated with treatment failure. Moreover, the high costs of these drugs and the high prevalence of Rabbit Polyclonal to HP1alpha HCV-infected individuals, especially in low-income countries, jeopardized the affordability for the healthcare system to treat all infected patients in developed countries and, even more, in developing countries [8, 9]. Finally, effective screening strategy is required to early identify and treat all HCV chronically infected patients thus limiting the infection transmission risk as well as the progression to SBC-110736 cirrhosis or hepatocellular carcinoma and reducing the healthcare costs [10, 11]. For all these reasons, a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally. This comprehensive review summarized the state of the art about three major unresolved issues in the fight against HCV: which are the perspectives for the universal screening of HCV? Do we need DAAs resistance testing in the future? How close is an effective preventive HCV vaccine? 2. Which Are the Perspectives for the Universal Screening of HCV? The rate of underdetection of HCV contamination is still relevant because of clinical, educational, technical, organizational, and economic issues. In fact, recent estimates suggest that most of people with HCV remain undiagnosed or unaware of their HCV contamination [12, 13]. Another criticism is represented by the difficulty in early diagnosing HCV infection. Indeed, few people are diagnosed during the acute phase because it is usually asymptomatic [14]. Furthermore, the 55C85% of persons who do not spontaneously clear the virus within 6 months develop chronic infection and remain asymptomatic for decades after infection, during which infection may be transmitted to other persons. Chronically infected patients usually become symptomatic when the HCV-induced liver damage is advanced and the therapy may be contraindicated [14]. The risk of late diagnosis is associated also with the limited access to HCV testing in many countries where HCV prevalence is high, such as African and Central-East Asian countries [15]. Therefore, it is crucial to implement the most sensitive and specific approaches to diagnose chronic HCV infection before the development of liver damage and to assure the SBC-110736 linkage to care of infected patients [16]. 2.1. Screening Tests for HCV Infection A testing strategy for HCV infections characterized by high sensitivity and specificity should be established. The WHO recommends offering the HCV serology test to individuals belonging to.Introduction Among infectious diseases, hepatitis C virus (HCV) still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. to early identifying and treating all HCV chronically infected patients. For all these reasons, even though new drugs may contribute to impacting HCV spread worldwide a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally, with the ultimate goal of its eradication. Advances in molecular vaccinology, together with a strong financial, political, and societal support, will enable reaching this fundamental success in the coming years. In this comprehensive review, the state of the art about these major topics in the fight against HCV and the future of research in these fields are discussed. 1. Introduction Among infectious diseases, hepatitis C virus (HCV) still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. Chronically infected individuals are estimated to reach 150C170 million worldwide and estimates of incidence, performed in the United States by the Center for disease control and prevention (CDC), reported nearly 30,000 new HCV infections in 2013 [1, 2]. Although HCV infection is characterized by a global diffusion, its prevalence greatly differs according to geographic area [3, 4]. Central Asia, Eastern Europe, the Midwest of North Africa region, and Central and Western Sub-Saharan Africa present high HCV prevalence rates, with figures ranging between 3.1% and 5.4%; regions with intermediate prevalence rates are Southern Sub-Saharan Africa, Central Europe, Australia, and Latin America, with values between 1% and 1.4%; low prevalence is found in Oceania (0.1%), Caribbean (0.8%), and Western Europe (0.9%) [3]. After acute infection, 75% of infected subjects become chronically infected and approximately 20% of this population develops liver cirrhosis during the two decades after infection if left untreated [5, 6]. However, since in most cases acute infection was asymptomatic, most HCV infections are clinically silent until the disease reaches a late stage: HCV was estimated to cause 25% of all cases of liver cirrhosis and cancer worldwide and to account for more than 500,000 deaths per year [7]. In recent years, substantial advances have been made to understand HCV biology and to develop a new generation of effective direct-acting antiviral agents (DAAs) able to cure HCV. However, several challenges hamper an effective control of HCV spread worldwide. In fact, the emergence of drug resistance and the suboptimal activity of these therapies against diverse HCV genotypes have been observed and have been associated with treatment failure. Moreover, the high costs of these drugs and the high prevalence of HCV-infected individuals, especially in low-income countries, jeopardized the affordability for the healthcare system to treat all infected patients in developed countries and, even more, in developing countries [8, 9]. Finally, effective screening strategy is required to early identify and treat all HCV chronically infected patients thus limiting the infection transmission risk as well as the progression to cirrhosis or hepatocellular carcinoma and reducing the healthcare costs [10, 11]. For all these reasons, a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally. This comprehensive review summarized the state of the art about three major unresolved issues in the fight against HCV: which are the perspectives for the universal screening of HCV? Do we need DAAs resistance testing in the future? How close is an effective preventive HCV vaccine? 2. Which Are the Perspectives for the Universal Screening of HCV? The rate of underdetection of HCV infection is still relevant because of clinical, educational, technical, organizational, and economic issues. In fact, recent estimates suggest that most of people with HCV remain undiagnosed or unaware of their HCV infection [12, 13]. Another criticism is represented by the difficulty in early diagnosing HCV infection. Indeed, few people are diagnosed during the acute phase because it is SBC-110736 usually asymptomatic [14]. Furthermore, the 55C85% of persons who do not spontaneously clear the virus within 6 months develop chronic infection and remain asymptomatic for decades after infection, during which infection may be transmitted to other persons. Chronically infected patients usually become symptomatic when the HCV-induced liver damage is advanced and the therapy may be contraindicated [14]. The risk of late diagnosis is associated also with the limited access to HCV testing in many countries where HCV prevalence is high, such as African and Central-East Asian countries [15]. Therefore, it is crucial to implement the most sensitive and specific approaches to diagnose chronic HCV infection before the development of liver damage and to assure the linkage to care of infected patients [16]. 2.1. Screening Tests for HCV Infection A testing strategy for HCV infections characterized by high.