Evolution in Tackling HCV: the Need to Change Paradigm

The hepatitis C virus (HCV) poses a significant public health challenge worldwide, with an estimated 57.8 million people chronically infected, of whom 3.9 million are in the European Union/Economic European Area (EU/EEA). A large proportion of people chronically infected with HCV are undiagnosed, as chronic infection is often asymptomatic. People in prison (PLP), people who use/have used drugs (PWUD), people living with HIV (PLWH) and those with chronic diseases at increased risk of iatrogenic transmission are disproportionately affected. The limited evidence shows that an estimated 398,610 people in Italy live with active HCV infection. The estimated prevalence of the infection varies regionally, with central regions reporting the highest rates (0.88%) and the northern regions exhibiting the lowest prevalence (0.54%). Italian surveillance efforts primarily focus on acute HCV cases, limiting the ability to comprehensively assess the burden of both acute asymptomatic and chronic infections. While extensive clinical cohort studies primarily support clinical research, only a few data linkage studies using administrative health records have been conducted. In Tuscany, a region with more than 3 million residents, research employing data-linkage methods estimated the prevalence of chronic HCV infection to be 1% at the end of 2015, aligning with other Italian studies. Based on the records available and using a capture-recapture method the estimated prevalence was 1%, which aligns with other studies in Italy. Introducing direct-acting antivirals (DAAs) has been a gamechanger in HCV treatment, prompting the establishment of elimination targets by 2030. The WHO has set ambitious goals for 2030, including diagnosing 90% of those with chronic infection and treating 80% of those eligible. The European Office of the WHO has developed a regional action plan to tailor these global targets to the regional epidemiological context. These efforts are reflected in Italy's National Plan for the Prevention of Viral Hepatitis (PNEV), endorsed by the Italian Ministry of Health in 2015. In Italy, DAA treatment has been available free-of-charge since 2014, initially limited to patients with severe disease, and monitored by the Italian Medicines Agency (AIFA) through a dedicated registry. In 2017, AIFA broadened the access criteria, allowing treatment for all individuals with detectable HCV RNA, regardless of liver fibrosis grade. In Tuscany, based on disease estimates, a triennial action plan was initiated in 2018 to enhance treatment coverage, aiming to treat over 6000 chronically infected individuals annually until 2020 as part of the broader strategy to eliminate HCV. Additionally, in 2021, a national one-time screening program targeting People in prison, PWUD, and individuals born between 1969 and 1989 was launched. However, the implementation of this program was hindered by the COVID-19 pandemic, affecting its rollout across Italy, including Tuscany. This Doctoral work represents an essential and comprehensive analysis a decade following the introduction of direct-acting antiviral medications, on the historical context of chronic HCV infection, the transformed methodologies for managing the care of individuals affected by the virus, and the anticipated developments in public health policies. This doctoral dissertation provides an in-depth analysis of the epidemiological trends associated with chronic HCV infection in the Tuscany region, tracing developments from the introduction of novel therapeutic agents to the present. It offers a thorough examination of the evolution of both national and local health policies, assessing their tangible effects on efforts to eliminate the virus, while aligning with the objectives set forth by the WHO for the year 2030. Policymakers will encounter new challenges, equipped with effective tools and robust data to formulate innovative eradication strategies. A critical focus will be on identifying undiagnosed asymptomatic cases and devising targeted approaches to curtail the transmission of the virus in confined or specialized environments, such as correctional facilities and harm reduction programs. Concurrently, advancements in the research of new medications and treatment protocols may enhance adherence to therapy among the general population and high-risk groups, thereby supporting established strategies that have demonstrated efficacy in treatment as prevention.