**4. Epidemiology and world impact of HCV**

HCV infection is one of the main causes of chronic liver disease worldwide, and according to recent estimates, until now more than 185 million people around the world have been infected. In addition, annually there are three million of new infected people, and among them 350,000 die every year due to HCV-related disorders [18–21]. The prevalence of HCV varies greatly, depending on the geographical area and the population considered: in Western Europe, it ranges from 0.4% to 3%; in Eastern Europe and the Middle East, it is higher but not precisely known [22]. The majority of the infected people reside in Asian countries (Taiwan, Mongolia, and Pakistan), sub-Saharan Africa (Cameroon, Burundi, and Gabon), and the Eastern Medi‐ terranean (Egypt), which holds the highest frequency, with more than 20% [18]. HCV is a major global public health issue due to its high prevalence, long-term unpredictable disease pro‐ gression, and low diagnosis and treatment response rates. Despite the fact that HCV infection rates are decreasing, the clinical and economic impact of chronic HCV infection is expected to considerably grow in the next decade since a large population of individuals that acquired the virus in the 1960s developed disease-associated health issues through to the 1980s [23]. The dual therapy, based on the administration of peg-IFN and RBV, is successful only in 40–50% of patients infected with the GT-1, while untreated individuals or who failed treatment are at risk of developing severe liver injuries such as cirrhosis, liver transplantation, and hepatocel‐ lular carcinoma (HCC) [24]. In Europe, there are 30,000 people on the transplant waiting list but only 12,000 procedures per year, and the average cost of liver transplant in the United States varies between \$139,000 and \$400,000 [25]. Although HCV can be successfully treated by now using antiviral therapy based on the administration of new direct acting antivirals (DAAs), the economic burden of the disease, including complex regimens and the cost of treatment, remains high since health care costs continue to rise [26]. For this reason, many HCV-diagnosed patients around the world are left untreated or undertreated. A 2010 study performed on U.S. employments found that the cost of sick days and lower productivity per HCV-infected workers was US\$8,352 per year [25]. A U.S. survey by the American Gastroen‐ terological Association (AGA) indicated that the cost for 30,000 outpatient visits for HCV infection amounted to US\$24 million in the 1998 [27]. The median cost for treating one patient with dual therapy (peg-IFN and RBV) ranges from €7,517 to €21,229, depending on the virus genotype, plus the costs of the new DAAs are about US\$70,100 per quality-adjusted life years (QALY) for mild fibrosis and US\$36,300 per QALY for advanced fibrosis [28].
