**10. Conclusions and challenges for the future**

The advent of DAAs and interferon-free strategies has substantially improved the clinical outcome in HCV therapy. Some interferon-free regimens have recently been licensed, and some other are in clinical development. These new combinations have shown high SVR, ranging from 90% to 100% even with shorter courses (8–12 weeks) of treatment, especially in low responsive population with dual and triple therapies. Current studies focus on the clinical development of a new generation of DAAs, such as the combination of ABT 493 and ABT 530, sofosbuvir, and GS-5816, gazoprevir, and elbasvir, which will be available in the near future as therapeutic strategies with high efficacy and short regimen (4–8 weeks). However, both scientific and economic unresolved issues are still present.

For the scientific perspectives, new and larger clinical studies are required in subjects infected with GT-3, in treatment-experienced patients and at advanced stages of the disease, which remain the most difficult subpopulations to be treated [144,145].

From the economic point of view, even though the new medications for hepatitis C are effective disease modifiers and have the potential, in a long-term perspective, to eradicate the pathology, the costs of new treatments are unlikely to be sustainable for the NHSs. Indeed, new pharma‐ ceutical policy and a global commitment are required to improve strategies of treatment and price negotiation with pharmaceutical companies to move from a theoretical cost-effectiveness approach to a practical cost-sustainable reality. Even if curing hepatitis C saves lives and prevents a lot of downstream health care costs related to the progression of the disease, including liver cancer or requirement of transplant, payers and politicians are in an uproar for a variety of reasons, not least the fact that the drug is priced much higher in the United States than in the rest of the world. For example, in Europe, where the government negotiates the price, the cost of sofosbuvir is on the order of \$55,000/patient. The ongoing discussion about the sustainability of the new treatments demonstrates the limit of the current health technology assessment classical approach. Indeed, the new products can be cost-effective in a long-term perspective, considering the avoidance of further hospitalization and medicalization costs related with transplantation. Until it will not be possible to reorganize the complete process of therapy, to be able to capitalize the expected savings, the cost-effectiveness evaluation will remain just a theory, posing concrete challenge to the sustainability of NHS systems. On the other hand, the proposed cost of treatment is still considered too high in relation to the prevalence of the pathology. This situation has opened the discussion on the necessity to find new reimbursement approaches and new level of cooperation between different States. In Europe, for example, bracket list price (min–max) for sofosbuvir has been proposed, to be adjusted for instance by GDP/Pro-capita income (e.g., differential price), prevalence (price/ volume), and/or adaptive reimbursement considering genotyping, subclusters, and time to event. None of the possible solutions have been implemented in a coordinated manner, but the access to HCV new treatments stimulated, among health care decision makers, the consciousness of the need of a new global synergistic approach.
