Hepatitis C virus infection in Irish drug users and prisoners – a scoping review

Hepatitis C virus (HCV) infection is a major public health concern globally. In developed countries iatrogenic transmission of HCV has been substantially reduced and people who inject drugs (PWID) or have done so in the past are now the main group affected [1‐5]. Of the 600,000 HCV infected people living in Europe an estimated 20,000–30,000 reside in Ireland [6‐9]. An estimated 60% of HCV infections in Ireland remain undiagnosed [6, 10].

Ongoing criminalisation of drug users ensure high levels of HCV in prison populations globally. It is estimated that a quarter of the global prison population have been exposed to HCV infection [11‐13].

Historically in Ireland, HCV transmission has occurred through infected blood and blood products with the majority of these infections occurring between the 1970s and the early 1990s [14]. Prior to the introduction of routine screening of Irish blood donations (1991), approximately 1700 people were infected through blood and blood products [6, 14]. HCV infection has been a notifiable disease in Ireland since 2004. Between 2004 and 2017, 14,107 cases were notified by the diagnosing laboratory with a peak in 2007 (n = 1539) [15]. In recent years there has been a decrease in cases notified with the number of new cases stabilising [15]. In 2012, the case definition was altered to specifically exclude resolved cases of HCV infection which may explain part of the reduction in the number of cases notified after this date [6]. Although there were no notifications of HCV infection prior to 2004, diagnostic data from the National Virus Reference Laboratory (NVRL) estimates that approximately 10,000 individuals were diagnosed with HCV infection between 1989 and 2004 [6]. A 2012 mathematical modelling study estimated the national prevalence of chronic hepatitis C in the Irish general population as 0.5–1.2% (20,000-50,000) [6]. A more recent lab-based residual sera study reported a prevalence estimate of 0.5-0.7% (20,000-30,000) [9]. Genotypes 1 and 3 are the types most commonly seen in Ireland and are distributed 55 and 45% respectively [16]. These are estimates of prevalence and the true prevalence rate in Ireland is unknown. There is no general screening of the population to determine prevalence rates with most studies only assessing the prevalence within specific risk groups [17, 18].

The estimates of prevalence however do indicate that in the general population the prevalence of hepatitis C is low, and most cases are from a defined risk group mainly PWID, people who received unscreened blood or blood products and people who were born in hepatitis C endemic countries [10].

Hepatitis C related morbidity and mortality continues to increase in Ireland, with increased hospital admission for, HCV related end stage liver disease (ESLD), hepatocellular cancer (HCC) and liver transplant [10]. This increase is likely related to the fact that the peak incidence of HCV infection in Irish PWID was in the late 1990s, and those infected during this period are now developing ESLD or HCC [19].

Since 2010 risk factor information has been available for 57% of notified chronic HCV cases in Ireland [6, 10, 14]. This data show injecting drug use (IDU) is the most common risk factor reported (80%), followed by possible sexual exposure (5%), receipt of blood or blood products (4%), vertical transmission (2%) and tattooing or body piercing (1%) (3). No risk factor was identified in 7% of notified cases [14].

The most significant risk factor for the transmission of HCV infection in Ireland is through injecting heroin. Capture-recapture studies carried out between 2001 and 2014 indicate that there are a significant number of problem opiate users in Ireland. The national point prevalence estimate of opiate users in 2014 was 18,988, giving a rate of 6.18 per thousand population aged 15–64 years (95% CI: 6.09–6.98). The prevalence of problem opiate use in Ireland has stabilised but remains amongst the highest in Europe [20]. Recent national trends indicate that the incidence of injecting opiates is declining [21]. There has been a steady decline in the total number of new entrants to treatment reporting opiates as their main problem drug with a drop from 58.1% in 2010 to 47% in 2016 [22]. The percentage who had ever injected among new treatment entrants for problem opiate use has also decreased significantly over time from 71% in 2004 to 64% in 2015 [21].

The Irish government introduced opiate substitution therapy (OST) and needle exchange programmes in Ireland in 1989 in response to an increasing HIV prevalence in PWID. OST is now provided nationally through a network of specialised HSE outpatient treatment clinics/satellite clinics, specially trained level 1 and 2 general practitioners in the community and prisons [23]. All OST patients are registered on a central treatment list (CTL). The number of clients on this list has increased each year since 2006 and there are now over 10,000 people on OST in Ireland [23].

The ongoing criminalisation of drug users in Ireland impacts on the levels of HCV infection in Irish prison populations. Over 60% of the 3400 prisoners incarcerated on a daily basis have a history of drug use with over a quarter reporting a history of IDU [13]. It is recognised that the majority of Irish prisoners come from marginalised communities with high levels of poverty, social deprivation, unemployment, illiteracy, physical and mental illness including addiction and blood borne virus (BBV) infections [24]. Like other prisoners, Irish inmates are identified as a hard to reach group for medical interventions and have poor access and uptake of traditional community medical services [24, 25].

Like other European countries, Ireland is upscaling HCV screening and treatment services [14, 26‐28]. Direct acting anti-virals (DAA), mobile elastography and the movement of HCV treatment in the community, coupled with less restrictive HCV treatment guidelines have revolutionised the HCV treatment landscape [29‐32]. Ireland’s national treatment program has signed up to the Global Health Sector Strategy on viral hepatitis for 2016–2020. The program aims to eliminate HCV as a major public health threat in Ireland by 2030 [33]. The roll out of new highly effective treatment in Ireland offers an exciting opportunity to achieve this goal yet many challenges to up scaling HCV screening and treatment to effective levels still remain. Understanding the burden of HCV disease and the barriers to screening, assessment, treatment and prevention in people who use drugs (PWUD) and prisoners in an Irish context is imperative in the planning and implementation of an effective national HCV strategy.

This scoping review collects and summarises the literature on HCV infection in PWUD and prisoners residing in Ireland. This review can, act as a baseline by which to monitor progress, support focused action and inform national and international public health HCV elimination strategies that target PWUD and prisoners as key at risk populations. This review also aims to identify gaps in the Irish-based HCV literature related to PWUD and prisoners and assess how these impacts on strategy development and service delivery.

This scoping review of HCV infection in drug users and prisoners in Ireland was conducted by applying the methodological framework set out by Levac and colleagues which was based on prior work by Arksey & O’Malley [34, 35]. The steps include; identifying the research question, identifying all relevant studies, selecting significant studies, charting the relevant data and then summarising and reporting the results. The rationale for using this methodology was to determine what is known about HCV infection in Irish PWUD and prisoners by reviewing all available literature (quantitative, qualitative, guidelines and policy documents) on these two groups and to map the key findings and concepts emerging from this body of literature. A further aim was to map gaps in the literature which will inform future research.

A broad search strategy was conducted in order to identify all relevant studies. Databases searched included PubMed, Science Direct, EMBASE, PsycINFO, Cochrane library and Medline. No limits were placed on dates. The key terms we used for this search were the MeSH terms, “hepatitis C” and [“prison” or “prisoner”] and “drug users” and “Ireland” or similar non-MeSH terms outside PubMed (Additional file 1). Follow up search strategies included hand searching relevant national websites including the Health Service Executive (HSE), Irish Prison Service (IPS), Departments of Health and Justice (DOH and DJ), the Irish Penal Reform Trust (IPRT), Health Surveillance Protection Centre (HSPC) and European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). National experts and authors of existing papers were contacted to identify possible sources of unpublished and grey literature. Reference list were also manually searched by the team to identify relevant studies or literature not captured. References were managed by the citation manager Endnote®. This software facilitated the recording and organisation of all relevant literature and also allowed for the cross checking of data records, removal of duplicates and extraction of information from the papers included in the review. The literature search was completed in June 2018.

Eligibility criteria for study selection centred on whether studies broadly reported on any aspect of HCV infection in Irish PWUD or prisoners including those that reported findings from analysis of these groups within broader populations. Publications to be included were peer-reviewed research, published reports, guidelines and strategies, editorials, commentaries and audits. Articles were excluded if they did not report results on these specific cohorts. Researcher 1(DC) analysed all articles found by title to select those that were potentially relevant. The abstracts of all studies selected based on their titles were independently evaluated by researcher 2(RM) and any discrepancies were kept in the analysis.

Data was extracted and charted from all studies selected at the abstract stage, using an instrument designed for this study covering; date and author, setting, study population and sample size, data collection period, study design, HCV prevalence and associated risk factors, HCV incidence, treatment outcomes, barriers and facilitators to HCV care, knowledge and experience of living with HCV, recommendations on the management of HCV and other outcomes. Data was extracted for each paper by a single researcher (DC) and checked by a second researcher (RM) to ensure that data extraction was accurate and comprehensive. The final decision to include studies was made based on this data extraction and whether it met the inclusion/exclusion criteria, based on independent evaluation by two authors (DC and RM), and a discussion of any discrepancies with the third author (TMcH).

A qualitative synthesis of the literature was carried out. The process of navigating and redefining the findings was iterative, and the researchers engaged with each stage in a reflexive manner, by fine tuning and repeating steps so as to ensure comprehensive synthesis of literature. Papers reporting on HCV incidence, prevalence, risk factors and screening uptake were categorised as epidemiological and reported and interpreted according to year of publication. For ease of reporting and interpretation this largest category was sub-categorised into those published in the last decade (2008–2018) and more historical studies published before 2008. The identified studies in this category reported on different populations (prisoners, PWID and PWUD on OST) and settings (prison, drug treatment centres and general practice).

The majority of the relevant literature retrieved from the web-site searches were either national reports, strategy documents or guidelines and were categorised as such. Studies reporting on outcomes following HCV diagnosis (self –clearance and sustained virologic response (SVR)) were categorised as treatment outcomes. The remaining literature was a mix of qualitative and quantitative studies that reported on a variety of outcomes including HCV –related health issues, alcohol consumption and patient and health provider experience of HCV infection and/or treatment and for convenience of reporting were categorised into HCV-related health issues and patient and health- providers’ experience. Where studies reported on a number of outcomes that crossed categories, these studies are categorised in the tables according to main/primary outcome and each outcome is reported in the result section according to its appropriate category.

Initial screening identified a total of 160 of which 27 were from grey literature and manual searching of reference lists. 117 met the inclusion criteria on title. Following a review of abstracts 42 studies were excluded. The remaining 75 studies were read in full and a further 17 were excluded. A total of 58 studies covering the period 1983–2018, were included in the final data synthesis (Fig. 1).

Five broad categories were identified to assist in the organisation of the literature. These were; Epidemiology, Guidelines and Policy, Treatment Outcomes, HCV -related Health Issues and qualitative research reporting on Patients’ and Health Providers’ Experiences.

For clarity the epidemiological studies have been grouped into studies reporting on HCV incidence and prevalence pre and post 2008. Within these time frames the studies are further categorised according to study population (prisoner, PWID and PWUD) and community location (drug treatment centre or primary care). The findings from studies reporting on risk factors and HCV screening uptake along with identified gaps in surveillance data are reported at the end of this section.

Overall this review found a larger than expected quantity and greater scope of literature published on HCV infection in Irish prisoners and PWUD. The literature was both quantitative and qualitative, employed many different methodologies and covered a 35-year period from 1983 to 2018.

The majority of the studies are epidemiological and report on HCV prevalence in both cohorts. This scoping review found that Ireland has low rates of HCV infection in the general population compared to other European countries [5, 27, 86, 87]. The most up to data (residual sera study) showed a reduced prevalence compared to a 2012 mathematical modelling study [6, 9]. The different rates could be explained by the differing methodologies or by a reduction in new infections. The absence of a population prevalence study makes it difficult to have a true HCV population estimate and impacts on the development of strategies to identify the undiagnosed population [6, 88].

This review found that IDU is the most common risk factor for HCV acquisition in Ireland and that the prevalence of HCV infection in Irish prisoners and PWUD is much higher than the general population. The prison-based studies included in the review found a reducing HCV prevalence with the most recent study (2014) reporting a prevalence of 13% [13]. This is much lower than the global estimates of 25% [11] but similar to other European country estimates [5]. The prevalence of HCV in all groups of PWUD and PWID is over 50%. Again, this is in keeping with other global and European estimates for this group [2, 5]. The majority of the studies included in the review are over a decade old, only include drug users on OST and all but two are Dublin based. There is a paucity of up to date literature on HCV prevalence in PWUD from outside Dublin and none at all on PWUD not on OST. A small number of studies reported on rates of chronic infection, but no study reported on the population based chronic HCV prevalence. This is a significant deficit in the literature as it does not allow for accurate estimates of untreated HCV infections and re-infections [89].

This review also found low levels of RNA testing for those identified as anti-HCV positive. Consideration should be given too adapting a reflex-RNA testing approach to HCV screening in Ireland [10]. This has the potential to reduce the number of bloods required in a group where venepuncture can be difficult and an indemnified barrier to engagement in HCV care [90]. As Ireland scales up HCV screening and treatment it is important that accurate data on levels of active HCV infection is available to optimise and evaluate the effectiveness of the national HCV strategy.

This review identified significant strategy, policy and guideline documents published over the last 14 years related to HCV. These provide a broader national context in which to interpret the literature and allow for comparisons to made with international and European strategies aimed at HCV elimination [27, 28]. However, it is concerning that the national strategy was published in 2012 and much of its content relates to interferon-based treatments and related challenges [14]. While the NHCTP provides up to date recommendations on HCV treatment [26], a new strategy is required to support the upscaling of HCV care, in particular, its movement into community addiction services and primary care. The national screening guidelines provide a useful guide to active HCV case identification [10]. These guidelines need to be underpinned with adequate resources and an evaluation to measure their effectiveness in identifies what is considered to be a significant level of hidden HCV infection in Ireland [6].

A handful of studies in this review report on treatment uptake and outcomes and on the lived experience of Irish HCV infected prisoners and PWUD [43, 44, 57, 83]. The evidence suggests poor uptake by HCV infected community PWUD with hospital-based services. This review also identified the many barriers related to HCV treatment uptake by this group [73, 83]. Many of these barriers are associated with previous interferon-based treatment and will be eliminated by the availability of DAA [29, 30]. This review also reports a number of facilitators to HCV engagement by Irish PWUD including the movement of HCV treatment out of specialised hospital services into community OST clinics. The success of this approach has been reported previously in the literature [91, 92] and is now the strategy being adapted the NHCTP [26]. This review found that treatment outcomes were not negatively impacted by patients having a history of IDU, however active drug use was identified as having a negative impact on treatment engagement. These findings need to be viewed with caution since they are related to interferon-based treatments [77]. Many patients were excluded from accessing treatment based on; a history of active IDU, excess alcohol or other drug use, concerns regarding relapse or mental health issues [91, 93]. Treatment was also only provided in specialist hospital services and only imitated after many hospital visits. This ensured that only the most stable and compliant PWUD accessed treatment. Broadening treatment eligibility. Increasing treatment locations and the use of short acting pangenotypic DAA will engage many less stable PWUD with HCV care [29, 30]. It is important the real-world data is available to monitor SVR post treatment and re-infection rates [94]. Similar to other published studies this review found SVR rates in prisoners equal or better that in the community [95, 96]. But challenges remain in screening and engaging more prisoners in HCV care [97]. This review found no studies reporting on prison-based barriers and facilitators to HCV care.

There is very little data available on the levels of HCV related liver disease in PWID and prisoners [98]. Where available, the evidence supports increasing levels of morbidity and mortality in these groups [98, 99]. This review found that HCV infection was associated with increased mortality and that problem alcohol use was common among HCV infected PWUD. Irish epidemiological studies report that there is an aging cohort of HCV infected PWUD, the majority having the infection for over 10 years. It is reasonable to expect that there is significant related liver disease in this cohort. While this group where initially prioritised for DDA treatment there is no data on how many of this high-risk group remain untreated. Studies on rates of HCV related liver disease and treatment uptake in this high-risk groups are required to ensure that are treatment strategies are successful in reducing HCV related morbidity and mortality.

Noticeable gaps identified in the literature on HCV in Irish prisoners and PWUD was the lack of studies, on strategies to prevent HCV infection and rates of incident infection in both groups. Ireland has a well-established network of harm reduction services including OST and needle exchange programs which are known to be effective in reducing HCV infection if provided with adequate coverage [100, 101]. However, there is no data available on their effectiveness in an Irish setting. Monitoring the rates of new infections will provide an indicator to the success of harm reduction services and the impact of treatment as prevention as more people are successfully treated with SVR.

This review summarises the literature on HCV in Irish PWUD and prisoners. The findings show that in Ireland, 0.5% of the general population have chronic HCV infection (60% undiagnosed), 13% of prisoners and over 50% of PWUD on OST have been exposed to HCV infection. People with a history of injecting heroin carry the greatest HCV disease burden in Ireland, with the majority having the infection for greater than 10 years. Increasing HCV related morbidity and mortality in this cohort, particularly in those with problem alcohol use is a concern. Irish PWUD engage poorly with hospital-based services and many barriers to HCV treatment uptake in this cohort have been identified. HCV treatment outcomes in Irish PWID is similar to other patient groups. In-reach hepatology services to Irish prisons has a positive impact on both uptake and successful completion of HCV treatment and its expansion to all prisons in Ireland should be considered. This review identified a range of policy and strategy documents that can inform national HCV screening, treatment and prevention programmes. A number of gaps in the literature were identified including; lack of reliable national prevalence data on untreated HCV infection (general population, PWUD and prisoners), accurate estimates of HCV related disease burden, HCV incidence infection in both PWUD and prisoners, barriers and facilitators to prisoners engaging with HCV services and HCV treatment uptake and outcomes in both groups. The lack of HCV epidemiolocal data on PWUD outside of Dublin and those not on OST is a concern. It is also important that policy and strategy documents are kept current to reflect international evidence-based practice and are informed by more accurate HCV surveillance data. This review is timely as Ireland scales up community-based HCV screening and treatment and gathers the available literature on HCV in Irish PWUD and prisoners. It is a useful starting point and can be used as a baseline to measure our efforts to eliminate HCV infection as a major Irish public health problem.