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The major advances achieved in the treatment of HCV by the development of new direct-acting antiviral agents (DAAs) allow treatment of almost the entire spectrum of patients with chornic infection. As a result of the exceedingly high cost of DAAs in many countries, IFN-free DAA regimens are mostly reserved to patients with advanced fibrosis or cirrhosis. Hence, treatment of patients with milder liver disease is often deferred. This could ultimately result in an increased burden of advanced liver disease and in increased long-term costs of management. Moreover, studies performed during the ‘interferon era’ and the early data on interferon-free regimens show that patients without severe fibrosis achieve higher rates of sustained virological response with less treatment-related adverse events. Unfortunately, there is no univocal way to predict the progression of liver fibrosis and therefore to identify the patients with early disease who would require urgent HCV treatment. Many studies have also demonstrated that treatment-induced HCV clearance reduces all-cause mortality regardless of the stage of liver fibrosis, pointing to an effect on extrahepatic manifestations of HCV infection. Last but not least, pharmacoeconomic studies show that DAA treatment of patients with mild HCV disease is cost-effective even at high prices of drugs, thus suggesting the opprtunity to treat regardless of the stage of liver disease.