This mixed-method study consists of two parts. Part 1 is a multi-center observational cohort study that will study the effectiveness of the structured implementation of CAC in a PWUD population receiving addiction care. Part 2 is a qualitative study using semi-structured interviews regarding addiction care professionals’ personal perspective on barriers and facilitators for implementation of the CAC pathway. We will focus on addiction care specialists and nurses, as well as board members in addiction care as all play a vital role in successful implementation of decentralization projects. The interviews will either take place face-to-face or digitally using a videoconferencing platform. The interviews will be audio recorded and transcribed verbatim. The mixed-method design will be integrated into the RE-AIM framework to allow for evaluation using a well-established method for implementing community-based health interventions. The RE-AIM framework facilitates the translation of research to practice with attention for contextual factors, as opposed to only efficacy or effectiveness [20]. RE-AIM involves evaluation in five dimensions (Reach, Effectiveness, Adoption, Implementation, Maintenance), resulting in a more explicit description of the strategy. RE-AIM has been used extensively in over 450 publications on study planning or intervention evaluation [21].

The CAC pathway is a new approach to HCV care in the Dutch addiction care setting, in line with regular HCV care guidelines [9, 10]. All five addiction care organizations in the Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA) collaboration will be invited to participate but we will also reach out to other major addiction care organizations to achieve nationwide coverage. All centers will be invited within a timeframe of two months. There will be no financial compensation for participation, however participation will include free education on hepatitis C. We anticipate that at least four out of five NISPA organizations and at least two non-NISPA organizations will participate. We will focus on centers that provide outpatient care, outreaching care or methadone posts, as these settings will contain most patients at risk for bloodborne infections and be suitable to provide hepatitis C care. Unfortunately, inpatient hepatitis C treatment is not currently reimbursed in the Netherlands. All phases of HCV care tasks are shifted to the addiction care physicians (ACP) and nurses, from case finding in patients with a risk for bloodborne infections to counselling, testing, treatment and follow-up. Patients at risk who visit the participating centers will be educated on viral hepatitis and HIV and motivated to undergo venipuncture. In the majority of patients, pangenotypic DAA treatment will be provided by the ACP after evaluation of biomarker panels (Fig. 1).

CAC flowchart *decompensated cirrhosis as indicated by FIB-4 score (> 3.25) and Child–Pugh score B or C; compensated cirrhosis as indicated by FIB-4 score (> 3.25) and Child–Pugh score A

CAC is a project that is part of the portfolio that is offered by HepNed, a collaboration between hepatologists and infectious disease physicians. HepNed coordinated the nationwide hepatitis C retrieval program CELINE [22]. During the CAC project, as addiction care teams are familiarized with HCV care, a HepNed expert is available for advice and instruction. In some cases treatment provided by a viral hepatitis expert is preferred: in patients with co-infection hepatitis B or HIV, renal impairment (eGFR < 30 ml/min/1.73m2) and in patients who previously failed DAA therapy or patients who present with decompensated cirrhosis (Child–Pugh B and C). In case of advanced fibrosis or compensated cirrhosis (Fib-4 > 3,25 and Child–Pugh A), patients receive hepatitis C treatment in addiction care and are simultaneously referred for fibrosis analysis and cirrhosis follow-up in secondary care. Patients who fail treatment will be referred to specialist care. After completing the treatment, patients will be counselled and reintroduced into established health screening programs. Patients with an HCV reinfection will be treated as new patients and can be treated on-site again.

Implementation requires a dynamic and tailored approach to the local situation in the individual addiction care center based on variation in availability of on-site venipuncture, outreaching healthcare providers and existing collaborations with viral hepatitis experts. Derived from barriers found in previous studies, CAC interventions include DAA provision in methadone distribution posts and a limit to excess blood withdrawals by testing in combination with health screenings and implementation of reflex HCV-RNA testing.

In Part 1 addiction care physicians will invite consecutive people who inject(ed) drugs or have other risk factors for HCV infection and who visit the CAC addiction care centers to participate. In order to be eligible for this study, a subject must be aged 18 years or older and able and willing to give informed consent. For the duration of the project, as many patients as possible will be included. There are no exclusion criteria for this study. Patients will be followed-up until the end of their HCV care journey. Since the CAC pathway is standard care in a decentralized setting, no comparison group can be formed. In part 2 we will invite addiction care physicians, nurses and addiction care policy makers employed both in centers participating in CAC and centers who do not.

The primary outcome in part 1 is HCV viral elimination, defined as percentage of patients that achieved SVR among identified HCV RNA positive patients. Secondary outcomes are total number of patients tested, prevalence of HCV antibody and RNA positivity among tested patients, fibrosis stage in HCV positive patients as found by FIB-4 and/or Child–Pugh scores, decentralized treatment initiation rate, treatment completion, sustained virologic response rate and referral. The main study outcomes for part 2 are the barriers and facilitators contributing to (un)successful implementation of the HCV care pathway for PWUD in the Netherlands.

The main study parameters collected are: acceptance rate of (on-site) testing, HCV prevalence, treatment acceptance rate, sustained virologic response (SVR) rates and re-infection rates. Furthermore, we will collect data on patient characteristics such as sex, age, history of drug use, medical history and comorbidities (including previous HCV infection and treatment), concomitant medication and available HCV-related clinical data (e.g. other risk factors, blood test results, liver fibrosis stage). All these parameters are stored in the electronic patient files by the patient’s treatment team as part of standard care. Data will then be collected anonymously by a member of the research staff according to the medical code of conduct [23]. A validated and GCP compliant data management program, CastorEDC, will be used for central data storage.

Interview recordings in part 2 of the study will be anonymized and used solely by the researches. The interview guide will address the following topics: preferred role of addiction center in HCV care: specifically for diagnosis, treatment and follow-up; experience and viewpoint on fully decentralized HCV care; real and anticipated barriers and facilitators for successful and sustainable implementation. Interviewee data collected includes participant characteristics such as sex, age, occupation and years of experience.

For the quantative study (part 1) we will use descriptive statistics. Primary and secondary endpoints, as well as baseline patient characteristics will be presented as percentages, means (± SD) or medians (IQR), depending on the variable and its distribution. No sample size is recorded as this is an observational prospective cohort study without a comparison group. All analyses will be performed using the statistical package SPSS, version 25.0 (SPSS Inc. Chicago, IL, USA).

In the qualitative study (part 2), Braun and Clarke’s approach to thematic analysis will be used to identify common themes across the interview transcripts [24]. The analysis will involve a six-phase process: familiarization with the transcripts, coding, searching for themes, reviewing themes, defining and naming themes and writing. The coding process will be data driven, in which codification is performed following an inductive method and themes are constructed from the data. Each transcript will be coded in pairs of 2 researchers. Qualitative thematic analysis will be performed using ATLAS.ti v9.1.6.

The Research Ethics Committee Arnhem-Nijmegen has waived formal ethical approval for this study, indicating it is not included in the Medical Research Involving Human Subjects Act. Eligible patients will be informed about the study by a member of the treatment team in the standard care pathway. While regular care continues as planned, patients are given sufficient time to consider participation in the study. Informed consent will be obtained before the collection of data by the coordinating researchers. Patients will be followed-up until the end of this study or until they withdraw consent. Due to the observational character of this study, participation poses no burden or risk for the participants. Participation leads to evaluation and may lead to improvement of the hepatitis care in addiction care facilities in the future, which benefits patients. Patients who decline participation in this study will still be offered access to onsite HCV care if the addiction care team can provide it.