A prospective, multicenter, collaborative study, based on the long-term active cooperation between two 3rd level units of Infectious Diseases and four 1st level clinical centers in southern Italy (Naples and Caserta – in the Campania region) was designed [13,14,15,16,17]. The study started in June 2018, was stopped in February 2020 because of the outbreak of SARS-CoV2 infection in Italy and was resumed in February 2021 until November 2021

The cities involved in the study host a large migrant population coming from low-income countries, especially from western Africa, middle and eastern Asia and Eastern Europe. Migrants from Africa move for economic reasons, to escape war and persecution, or to reunite with their family members. Migrants from Eastern Europe move for economic reasons or to reunite with their relatives [13,14,15,16,17].

The first-level clinical centers are general practice clinics that are attended mainly by migrants for low back pain, headache, itching, cough, hypertension and allergy symptoms; thus, they have proven experience in managing vulnerable groups and are greatly appreciated by the migrants. These first-level centers are linked with the Italian humanitarian organizations "La Caritas" the Tent of Abraham" and "Emergency", which welcome migrants who need help, offering refuge even if temporary, hot meals, and medical and legal assistance. The migrants willingly frequent these associations because they know they can find help, they know they can find competent people who try to help them obtain temporary documents, in order to find work and to join their families in other European countries [13,14,15,16,17].

Moreover, the present study program was facilitated by the work of cultural mediators, professional who facilitates the communication, including interpretation, between people speaking different languages and coming from different cultural backgrounds [18] and was a fundamental link between the physicians and the migrants.

By the term “migrant” as that “a person living in another country than he/she is born” and we refer to a heterogeneous population including undocumented migrants (persons moving outside regular migration channels), asylum seekers (individuals whose are seeking international protection for fleeing persecution or serious harm or for other reasons), refugees (people fleeing persecution or conflicts seeking international protection under the 1951 Refugee Convention on the Status of refugees) and economic migrants (people whose primary motivation for fleeing their home country is to improve their economical situation) [18].

We included both newly-arrived migrants and subjects who had been living in Italy for more than one year. We considered as “newly-arrived migrants” subjects living in Italy less than one year and as “anciently-arrived migrants” subjects living in Italy for more than one year.

Refugees have access to all the healthcare facilities of the National Health System; for undocumented migrants access is limited to minors, pregnant women and patients with severe pathological conditions or communicable diseases.

All ≥ 18 years old consecutively evaluated for clinical or legal consultation at one of the four first-level centers were enrolled in the present study program, organized in four phases (Fig. 1). Thanks to the collaboration between the cultural mediator and the physicians and nurses, all the subjects evaluated at the first level centers in the study period were offered to participate in the study.

Phases of the study and outcomes

The first part of the study included an "educational" phase: the physicians, with the help of cultural mediators, explained to the migrants who attended the first-level centers what were the main sexually and blood transmitted infectious diseases endemic in their countries of origin and information on the routes of transmission. The physicians indicated that the use of condoms protected them from sexually transmitted diseases and the use of personal sharp objects was a risk for blood transmitted infectious diseases; moreover, the natural history of HCV infection and of the other parenteral infectious diseases and the availability of very effective and safe antiviral therapy were explained. The information/education was done through meetings and using brochures with pictures and explanations translated into English, French and Swahili.

After the educational phase, at first-level medical centers pseudonymized serological screening (recording only the center number and patient's number) was offered to seek HIV, HBV and HCV in full accordance with the Italian privacy law regarding observational studies (second phase). The migrants, who agreed to join the study, signed an informed consent written in the immigrant's own language and filled out a pseudonymized questionnaire administered by the research investigators with the assistance of a cultural mediator on the demographic data (age, gender, race/ethnicity, place of birth, language), date (month and year) of immigration, socioeconomic status (level of education), religion, cohabitation details, sexual orientation and practices including condom use, history of HBV vaccination, surgery, dental care, tattooing, body piercing, use of drugs, blood transfusion, tribal rituals, abortion and information on previously documented personal and family infections of HBV, HCV and HIV. The data relating to the epidemiological characteristics were collected in an electronic database. The clinical history was obtained with the help of a physician and a cultural mediator during a prolonged, in-depth clinical consultation and counseling.

All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti-HCV and anti-HIV.

The sera of HBsAg-positive subjects were tested for serum HBV DNA anti-delta (data not shown). The sera of anti-HCV-positive subjects were tested for HCV-RNA.

The third part of the study included a "linkage-to-care" phase: the participants who were positive for HCV-RNA were referred for monitoring and possible treatment to one of the two tertiary units of infectious diseases operating in the same city. Obviously, also HBsAg and/or anti-HIV-positive subjected were linked-to-care to one of the two tertiary units participating in the study (data not shown). Also in this phase, cultural mediators played an important role because they accompanied migrants to third level centres . At the third-level infectious disease units, all the HCV-RNA-positive subjects were tested for HCV genotype.

The last phase of the present study program was the “treatment” phase. All the HCV-RNA-positive subjects were offered antiviral treatment. Migrants who agreed were treated with sofosbuvir-velpatasvir (Gilead Science) for 12 weeks and followed-up for 12 weeks until the end of therapy. The choice of sofosbuvir-velpatasvir was based on the use of a pan-genotype regimen with the same schedule both in cirrhotic and non-cirrhotic patients. Response to antiviral treatment was defined as sustained virological response (SVR: HCV-RNA undetectable) 12 weeks (SVR12) after the end of therapy. Relapse was defined as a reappearance of serum HCV-RNA after DAA treatment.

The end-points of the different phases of the present study were: for the screening phase, the proportion of screened subjects for HBV, HCV and HIV versus the number of evaluated subjects in the period study.

For the linkage-to-care phase, the proportion of HCV-RNA-positive participants evaluated at third-level infectious disease units versus all anti-HCV positive subjects; for the treatment phase, the proportion of HCV-RNA-positive-patients who started sofosbuvir-velpatasvir treatment versus all the HCV-RNA-positive-patients enrolled, and the SVR rate by an intention-to-treat analysis.

The study was approved by the Ethics Committee of the Azienda Ospedaliera Universitaria of the University of Campania Luigi Vanvitelli, Naples, Italy (214/2012; 481/2018). All procedures performed in this study were in accordance with the ethics standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethics standards.

This work was in part supported by Gilead, who supplied sofosbuvir/velpatasvir.

Serum samples were tested for HBsAg, total anti-HCV, anti-HIV, anti-HBc and hepatitis B surface antibodies (anti-HBs) by commercial immunoenzymatic assays [Abbott Laboratories, North Chicago, IL, United States: AxSYM HBsAg (V.2) M/S for HBsAg, AXSYM HCV 3.0 for anti-HCV, AXSYM HIV 0.5 COMBO for anti-HIV, AXSYM core for anti-HBc and AXSYM AUSAB for anti-HBs]. Anti-HIV reactivity was always confirmed by a Western blot assay (Genelabs Diagnostics, Science Park Drive, Singapore), which identifies both HIV-1 and HIV-2 strains. Anti-delta was tested in HBsAg-positive subjects by anti-HDV Elisa (Dia.pro diagnostic bioprobes, Sesto San Giovanni, Milano, Italy).

Serum HCV-RNA was quantified by a real-time PCR method in a Light cycler 1.5 (Roche Diagnostics, Branchburg, NJ, USA) with a limit of detection < 40 IU/ml, as previously reported [19, 20]. HCV genotypes were identified by the HCV genotype Lipa assay (Bayer, Lyon Cedx 09, France).

For the descriptive analysis, the categorical variables were reported as absolute numbers and relative frequencies. Continuous variables were summarized as mean and standard deviation (SD) if normally distributed, or as a median and interquartile range (IQR) if not normally distributed.

We used Pearson chi-square or Fisher’s exact test for categorical variables and Student’s t test or Mann–Whitney test for continuous variables. A P value < 0.05 was considered to be statistically significant. Analyses were performed with SPSS 21.0 (IBM, Armonk, NY, USA).