On-site testing and case management to improve hepatitis C care in drug users: a prospective, longitudinal, multicenter study in the DAA era

Chronic infection with the hepatitis C virus (HCV) remains a worldwide health problem. The World Health Organization (WHO) has set a target to reduce HCV infection incidence by 90% and liver-related mortality by 65% while increasing diagnosis and treatment by 2030 with the year 2015 as baseline [1]. With the development of direct-acting antivirals (DAA), HCV treatment has become very effective [2‐4].

The seroprevalence of hepatitis C virus (HCV) is relatively low (1.0%) in Belgium’s general population [5]. However, the prevalence is increased in several subpopulations and these high-risk populations can continue to transmit the virus if risk behavior persists (e.g., injecting drug) [6, 7].

Accordingly, at-risk populations such as people who use drugs (PWUD) should also be treated as they are responsible for the virus’s ongoing transmission [8].

A cascade of care is a well-known concept and pinpoints where gaps in services may exist and strategies can be developed to better support patients. However, only a few studies have evaluated the cascade of care in PWUD since the introduction of DAAs. These studies mainly focus on (active) people who inject drugs (PWID), which means that other risk subgroups such as stimulant users and former PWID are not reached [9‐12]. A large study in British Colombia, Canada, showed that active PWID had the highest rates for HCV RNA testing, though the lowest for treatment initiation [13]. In addition, the treatment rates remained low in all studies, even in the DAA era.

Several barriers to HCV care may explain the lower rates of screening and treatment among drug users [14]. Studies show that both patients and caregivers lack knowledge about HCV infection, and stigmatization of HCV infection has a significant impact on admission for screening and treatment [15‐17]. In a recent systematic review, interventions to enhance HCV screening, linkage to care, and treatment initiation were evaluated [18]. Two interventions were shown to improve HCV screening: (1) on-site testing with pre-test counseling and education, and (2) dried blood spot testing [18‐20]. Furthermore, facilitated referral for HCV specialist evaluation and planning of specialist appointments improved linkage to care [21‐23]. Integrating HCV care in addiction care centers by a multidisciplinary team with case management services can also improve treatment rates [24, 25]. However, most studies were cross-sectional, performed in the interferon-era and PWID. Therefore, more longitudinal data are necessary from the DAA era to strive towards HCV elimination in PWUD.

Before 2015, there was no systematic approach to address HCV infection among PWUD in the Center for Alcohol and Drug abuse (CAD) Limburg in Belgium. A small randomized controlled trial (RCT) was conducted in 2014 at the addiction care center by Arain et al. to assess the influence on knowledge and willingness for HCV screening and treatment among PWUD. The single information session significantly improved HCV knowledge, though it did not result in higher rates for screening and treatment. However, the small number of subjects (n = 52) and the fact that the study was conducted in the interferon era should be considered when interpreting this study’s results [7]. Hence, an urgent need for an easy-to-implement model was needed to offer HCV care to PWUD in an addiction care center. Therefore, we conducted this study. We offered several targeted interventions (pre-test counseling, on-site testing, facilitated referral) to positively influence the HCV cascade of care in PWUD in the addiction care center in Limburg, Belgium.

More data are needed within the DAA era to identify strategies to enhance HCV testing, linkage to care, and treatment to reach the WHO’s goals [18]. This study presents an HCV care model, led by one case manager at an OAT center with different sites in Limburg, Belgium. The case manager contacted 90% of the PWUD attending the addiction care center and could screen 88% for HCV infection between 2015 and 2018. Thus, we exceed the 16% target, which shows that this care model’s implementation is very effective for HCV screening in PWUD in addiction care centers. Specific and novel to our multicenter model is that the case manager moved between the different sites to include PWUD actively and do an annual follow-up. Most importantly, due to the work of only one person, this care model has a tremendously positive and potentially enduring impact on HCV care among substance users across an entire province in Belgium.

Services such as information and education on HCV infection were integrated at the OAT center. Targeted on-site HCV screening was carried out at all the different locations of the OAT center. Previous studies to enhance uptake for screening by on-site testing with pre-test counseling varied widely, with testing rates from 18 to 86% in the interferon era [18, 36]. Nevertheless, we reported results in the DAA era, and our yearly screening rates varied from 76 to 86%, with a combined screening uptake of 89% over the 3 years. Moreover, as we compare our new results with the few data we have from before implementing this care model, the uptake of screening has increased enormously (from 9.5 to 89%). Our results point to a large, positive impact and the need to continue this care model.

In Belgium, DAA treatment can only be prescribed by a hepatologist. Therefore, specialist evaluation needed to be performed in the hospital. To enhance linkage to care, case management services were provided to facilitate referral and appointments, and PWUD were also accompanied to the hospital if requested. Internationally, studies showed increased linkage to care ranging from 51 to 82% in studies with on-site screening, education, and/or case management services [22, 23, 25, 36]. In our setting, specialist evaluation ranged from 69 to 77% yearly, with a combined linkage to care of 86% over 3 years.

Treatment initiation is the most difficult to compare with international findings. This differs the most due to novel, effective and safe treatments compared to the interferon era. Furthermore, the presence of (changing) reimbursement criteria makes a comparison between countries difficult [37, 38]. Previous studies in the interferon era demonstrated the effectiveness of interventions such as nurse-facilitated referral to the hospital and integrating HCV care on-site with non-invasive liver disease assessment and motivational education. Treatment rates ranged from 7 to 38% in these studies [21, 24, 39]. Nevertheless, we report results in the DAA era, and yearly treatment initiation ranged from 16 to 33%, with a combined treatment rate of 44%. The most important reason for refusal of therapy was located at the level of the health care system. First, 14% of all HCV RNA positives did not reach the hospital for specialist evaluation (no linkage to care). Additionally, 40% of those who reached the hospital for specialist evaluation did not reach the reimbursement criteria of a fibrosis stage ≥ F3 (2015) or ≥ F2 (2017). Of those eligible for treatment, five PWUD were refused therapy due to non-adherence. The decision to refuse therapy was always made with a multidisciplinary team (hepatologist, case manager and CAD staff). Three PWUD were incarcerated before therapy could be initiated. In Belgium, the Department of Justice regulates the prison system and not the Department of Health. Therefore, we could not initiate treatment for these patients under the supervision of the case manager. Currently, DAA treatment can only be prescribed and initiated by a hepatologist and is available only in a hospital pharmacy. If in the future, DAA therapy could be prescribed by other healthcare professionals and be available in local pharmacies, treatment access would improve, and patients would be able to receive their medication more conveniently.

PWUD on centralized OAT provision were more likely to be screened and linked to care than PWUD receiving decentralized OAT. Our intervention was implemented at the OAT center, so patients who visited often would more easily benefit from the case manager’s support. Also, PWUD receiving decentralized OAT were less likely to have injected drugs, were more often employed, and had more often stable housing. Housing instability is associated with high-risk injection behavior and impacts social networks [17, 40, 41]. Outreach will be implemented during the next years to improve screening and linkage to care for PWUD in decentralized OAT.

There were limitations to this study. Our study population consisted of PWUD, who were in contact with the OAT center. Therefore, they could already be more engaged in care and might not represent the whole PWUD population. Furthermore, our study was not an RCT due to the goal of providing HCV care to the whole population. Except for the small historical group studied by Arain et al. in 2014, there was no comparison possible, and the impact of the various steps of our care model could not be assessed well. As there was little to no data available from the period before our study intervention, a long-term comparison was difficult. Finally, we did not collect data on coinfections, which could potentially influence screening and treatment initiation.

Using the cascade of care to guide interventions is easy and necessary to monitor results. Since 2019, this project has been recognized and financially supported by the Flemish government. This population needs guidance, not only for screening and treatment but also for the long-term follow-up since one in six had cirrhosis and could develop HCC. Further interventions are necessary to increase linkage to care and treatment initiation. Universal access to DAA therapy from 2019 onwards will contribute significantly to reaching HCV elimination in our cohort.