Puglia HCV Micro-elimination Program

Scientific Rationale: To adhere to the WHO plan of identifying 90% and treat 80% of HCV infected subjects, in several Countries a number of barriers need to be overcome (1). A focused effort from physicians and public administrative authorities is required to increase HCV treatment rates using direct acting antivirals (DAAs). Consequently, methods enhancing the epidemiological impact of HCV treatment using DAAs are of primary importance in order to promote what has been defined as micro-elimination (2). Among populations at high risk of transmission, targeted in the context of developing micro-elimination, people who inject drugs (PWID) and, in general, subjects with substance use disorders (SUD) are particularly important to treat.

In Italy, individuals with SUD including people who inject drugs and subjects taking psychiatric medications or alcoholic excess represent the most important target of HCV micro-elimination. Data provided by the Italian National Institute of Health during 2017, show a decline in the incidence of acute HCV infection with a peak of 0.3 x 100.000 inhabitants among subjects of 25-34 years as a consequence of: recent or ongoing use of intra venous (i.v.) substances; and/or sexual transmission (3). Moreover, in the National Cohort Piter including 9.040 HCV infected subjects, 32% was or is currently using alcohol and about 20% was or is currently using substances (4). Of interest, while alcohol abuse is usually associated with cirrhosis, drug use is associated with any stage of fibrosis. These epidemiological data highlight the need to differentiate and personalize the approach to SUD people. Finally, it is important to mention that a decline in the rate of screening has recently been registered in Italy among subjects followed by Outpatient Services for substance use disorders called SERDS (5-6). Current estimates suggest that, in our region, about 4500 subject using substances are probably HCV infected (6). Although it seems that no more than 10% of regular SERDS patients have not yet been screened for viral infections the rate of unscreened people is increasing among young SERDS patients (7). A high rate of unscreened SUD partners and families has been reported by SERDS specialists in our geographical area (personal communications).

In our real life experience only 50% of SUD patients testing HCV RNA positive agree to be treated due to different reasons including fear of treatment and difficulties in reaching DAAs treatment prescribing centers (8). Furthermore, in recent real world study leaded by our center and involving 20 out of 31 of the authorized prescribing centers in Puglia, we observed a 3% higher rate of treatment discontinuation in this, versus general population (8).

Rapid and cost-effective interventional strategies may favor both diagnosis of unknown cases and access to treatment for eligible patients. In general, training and education for providers, and an increased awareness of new advanced DAAs therapies among key risk populations are activities to strengthen within the Health system. However, in given situations, diversifying services and ensuring geographically and culturally appropriate services may play a key role in increasing the screening-diagnosis-referral-treatment-follow up cascade. It is important to establish upfront, within the heath care physicians, what can be done by different figures: the prescriber gastroenterologist is allowed to prescribe DAA and able to manage patients with a very advanced disease or patients with multiple drug-to-drug interactions; and the specialists working at the SERD are not allowed to prescribe DAA but used to monitor SUD patients and to help them to recover from their disorders.

Hypothesis: In Italy, SERDS are spread over the regional areas. According to the geographical characteristics of Puglia and Molise, the region bordering Puglia to the north, there are peripheral areas either along the cost or in internal mountains not well served by the public transportation. This aspect results in the need of relying on a private car to reach the specialized center where patients can be screened, diagnosed and treated. Fifteen SERDS are present in Northern Puglia and Molise over an area of 7500 Km2 usually served by our Hepatology Unit.

Our hypothesis is that, in addition to the known barriers to care for SUD population, lack of direct and efficient public transport represents a limitation preventing SUD individuals not only from being screened, diagnosed and treated, but also adequately informed on the most recent and highly efficient and safe pan-genotypic regimens with low impact drug to drug interactions. Moreover, the chaotic lifestyle and the poor income conditions of these patients prevent treatment completion due to transportation issue, for those who start treatment.

Primary Objective: the primary aim of this project is to explore our hypothesis by evaluating the impact of intensifying screening, diagnosis, linkage to care and treatment cascade of SUD patients through a dedicated cure program including "ad hoc" transportation.

Secondary aims are: firstly, to increase the awareness on HCV infection and related liver disease through a peer-to-peer educational campaign performed at SERDs in combination with our Unit. (Risk and liver disease outcomes, diagnostic and staging tools and the new DAAs regimens will be explained either to patients or to local healthcare workers and nurses at each individual SERD). Secondarily, to reduce treatment discontinuation in the subgroup of PWID patients.