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

Background Hepatitis C infection is a major public health concern globally. In Ireland, like other European countries, people who use drugs (PWUD) and prisoners carry a larger HCV disease burden than the general population. Recent advances in HCV management have made HCV elimination across Europe a realistic goal. Engaging these two marginalised and underserved populations remains a challenge. The aim of this review was to map key findings and identify gaps in the literature (published and unpublished) on HCV infection in Irish PWUD and prisoners. Methods A scoping review guided by the methodological framework set out by Levac and colleagues (based on previous work by Arksey & O’Malley). Results A total of 58 studies were identified and divided into the following categories; Epidemiology, Guidelines and Policy, Treatment Outcomes, HCV-related Health Issues and qualitative research reporting on Patients’ and Health Providers’ Experiences. This review identified significantly higher rates of HCV infection among Irish prisoners and PWUD than the general population. There are high levels of undiagnosed and untreated HCV infection in both groups. There is poor engagement by Irish PWUD with HCV services and barriers have been identified. Prison hepatology nurse services have a positive impact on treatment uptake and outcomes. Identified gaps in the literature include; lack of accurate epidemiological data on incident infection, untreated chronic HCV infection particularly in PWUD living outside Dublin and those not engaged with OST. Conclusion Ireland like other European countries has high levels of undiagnosed and untreated HCV infection. Collecting, synthesising and identifying gaps in the available literature is timely and will inform national HCV screening, treatment and prevention strategies. Electronic supplementary material The online version of this article (10.1186/s12879-019-4218-6) contains supplementary material, which is available to authorized users.


Background
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][2][3][4][5]. Of the 600, 000 HCV infected people living in Europe an estimated 20,000-30,000 reside in Ireland [6][7][8][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][12][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][27][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][30][31][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.

Methods
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.

Results
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.

Epidemiology (32)
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.

Pre-2008 (22 studies) Incidence (2 studies)
Two studies reported on HCV incidence in the pre-2008 period. The first was a 2003 a single-site study on HCV negative PWID attending methadone maintenance treatment (MMT) at the National Drug Treatment Centre (NDTC). Follow up screening on 100 patients found an HCV incidence of 66 (CI 51-84) per 100-person years (py). A larger 2005 study involving 21 drug treatment centre sites and 1459 PWUD reported an incidence of 24.5 per 100 py. [36,37].
Prevalence (20 studies) (prisoners =3 studies, PWUD = 7 studies, PWID = 8 studies) A total of papers was identified reporting on the prevalence of HCV infection in PWUD and prisoners in Ireland dating from 1983 to 2008. Prisoners Two studies were prison-based, one a randomised national study of the general prison population, the other was conducted on committal prisoners only. The 2000 study of 9/15 prisons in the Republic of Ireland (ROI) reported an anti-HCV prevalence of 37%, increasing to 81% among those prisoners with a history of IDU. The 2001 multi-site committal study reported an anti-HCV prevalence of 3% in those who had never been imprisoned previously, 22% in prisoners aged 19-25, increasing to 72% in prisoners with a history of IDU [38]. An interesting 2000 prison-based study reported on the discrepancy between self-reported HCV status and actual status (confirmed by oral swabs). Based on self-report the HCV prevalence estimates were 19% but actual prevalence was double this rate (37%) with small numbers (5%) reporting being anti-HCV positive erroneously [16]. Nine studies reported on HCV prevalence in PWUD attending MMT in community drug treatment clinics. The first was a 2001 multi-site randomised chart review of 715 patients attending MMT. This study reports an anti-HCV prevalence of 78.8% which reduced to 52% in those under 25 [39]. The 2005 incidence study described above reported an HCV prevalence of 66% in a population of PWUD attending drug treatment across 21 sites in the Dublin region [37]. A single site study from the NDTC reports an anti-HCV prevalence of 81.6% among study participants attending the centre for MMT during a 3-month period in 2002 [40]. A unique 2004 study reported an anti-HCV prevalence of 27% among adolescent drug users attending drug treatment, increasing to 55% among those with a history IDU [41].
A 2003 study involving 531 PWUD attending MMT at 42 general practice locations reported an anti-HCV prevalence of 78% [42]. A single site 2005 study reported an anti-HCV prevalence of 88% [43]. A later 2007 multisite study reported an anti-HCV prevalence of 69% [44]. A 1983 paper reported on the identification of non-A non-B exposure in 90% of a cohort of PWID with acute hepatitis undergoing biopsy at a single hospital site in Dublin [45].
Four studies were single site studies from the NDTC (1995-2000) three of which were on new entrants with varying lengths of IDU history. Among new entrants HCV prevalence ranged from 52 to 61.8% [17,46,47]. The single 1995 study reporting on HCV prevalence among PWID on methadone maintenance treatment (MMT) reported an anti-HCV prevalence of 84% [48].
A 2003 single-site study was the first to report on the prevalence of chronic HCV infection and genotype distribution in a PWID cohort. Of the 94 included in the prevalence part of this study, 74.5% were anti-HCV positive, 41.5% where HCV-RNA positive (chronic HCV infection). The genotype distribution was 66.6% genotype 1 and 25.6% genotype 3. This study also included a mathematical modelling component to estimate national HCV burden levels [49]. These findings are reported in a later section of this review. A multi-site 2005 study involving 496 patient's mono-infected with HCV of whom 127 (with demonstrated self-clearance on initial testing) were followed up 2 years later. The initial testing showed a self-clearance of 38% which when followed up 2 years later had reduced to 31.1%. The genotype distribution reported in this study was genotype 1 = 48.8% and genotype 3 = 48.5% [50]. A 2005 multi -site study (10 sites including 2 residential drug treatment sites) reported an anti-HCV prevalence of 61% among PWID who had a history of IDU in the past 6 months but who had never tested for HCV [51].
Only one single-site study reported specifically on HCV infection in PWID in primary care. This unique longitudinal study followed a cohort of 82 PWID attending a south inner-city Dublin general practice over 25 years. At the beginning of the study HCV infection had not been identified but at 10-year follow-up, 33% of those still alive had been infected. At 25-year follow-up 40% of survivors were anti-HCV positive [52].

At -risk population associated with PWUD (2 studies)
Two studies reported on HCV prevalence in groups associated with PWUD. A single 2001 study reported that 82% of infants referred to an outpatient paediatric HCV clinic where from mothers with a history of IDU [53]. A 2008 study of homeless people found high levels of PWUD among this group (64%) as well as a high prevalence of HCV exposure (36%) [54] (Table 1).

Incidence (1 study)
A 2016 study using mathematical modelling and data on 14, 320 PWID registered on the NDTRS estimated that 12,423 (CI 10,799-13,161) PWID were infected with HCV from 1991 to 2014, 9317 (CI 8022-9996) of whom had chronic infection. This paper also reported that new infections peaked in 1997, and that almost three quarters of those infected have the disease for greater than 10 years [19].
• Among those reporting a previous negative result, 37% were positive on oral fluid assay.
• Median age of diagnosis is 28.
• 70% of those infected though drug users were male.
• Median age at diagnosis for those infected through drug use = 25 years for males and 23 years for females.
10.9-15.2%) among the general prison population, increasing to 41.5% in prisoners with a history of IDU and 54% in those with a history of injecting heroin [13]. The most recent prison study from 2014 (single -site) reported an HCV prevalence of 37% among prisoners on MMT [57].
Two 2014 studies identified from the grey literature reported on HCV infection in PWUD attending MMT in drug clinics outside of Dublin and reported an anti-HCV prevalence less than Dublin based studies (24%%) [58] (Horan A: Chart audit of HCV screening measuring the effect of chart labelling, unpublished). A published 2017 study reported an anti-HCV of 63.6% among PWUD attending MMT at a North Dublin inner city treatment centre [59]. Two recent large HCV screening audits, identified through the grey literature search, reported an anti-HCV prevalence of almost 80% and a chronic HCV prevalence of 65% among PWUD attending MMT at 23 drug treatment clinics in Dublin (Burke M: Audit of HCV screening using retrospective patient records, unpublished), (Burke M. Audit of HCV screening using retrospective patient records [Unpublished audit]). The most recent prevalence study in PWUD attending OST in general practice reported an anti-HCV prevalence of 77.2% among this group [60].

PWID (1 study)
A study conducted on PWID attending an inner-city accident and emergency department showed high levels of morbidity and HCV exposure (74%) [61] (Table 2).

HCV risk factors
A total of 13 studies (1995-2017) reported on risk factors for HCV acquisition in both prisoner and PWUD populations. Prisoner risk factors identified were; a history of IDU, sharing needles while incarcerated, sharing drug taking equipment, older age, female gender, a previous history of incarceration and a history of having a prison tattoo. [13,64,65]. For drug users attending community-based OST risk factors identified were; a history of IDU, increased total number of lifetime injecting, closer social relationships with PWID, injecting in the homes of other PWID, a history of imprisonment, older age, male gender, drug use prior to 1989, coinfected with HIV or HBV, younger age of first drug use, first IDU and entry to MMT and type of drug first used [6,17,36,37,39,42,48,51,53,59].

HCV screening uptake
A number of the epidemiological studies reported on HCV screening uptake among the study population. The first was a 2001 multi-site randomised chart review of 715 patients attending MMT. This study reports a screening uptake of 60%. The larger 2005 Dublin based multi-site study involving 1459 PWUD reported an 88% uptake of HCV screening.
A single site study from the NDTC reports very high levels of HCV screening uptake and an anti-HCV prevalence of 81.6% among study participants [40]. However only a third of anti-HCV patients were RNA tested showing a chronic HCV prevalence of 15.6%. This study also found high levels of accuracy for HCV self-report [40].
A 2003 study involving 531drug users attending MMT at 42 general practice locations reported that over two thirds had an HCV screen [42]. Two large HCV screening audits, identified through the grey literature search, reported high levels of HCV screening (Burke M: Audit of HCV screening using retrospective patient records, unpublished),(Burke M. Audit of HCV screening using retrospective patient records [Unpublished audit]). Dublin. Uptake of HCV screening was less than in Dublin clinics (50%) (Horan, 2014; Ryan & Ryan, 2014) The Cork (second largest city in Ireland) study identified that chart labelling (starring) had a positive impact on the uptake of screening among this patient cohort (Horan A: Chart audit of HCV screening measuring the effect of chart labelling, unpublished). The most recent prevalence study in PWUD attending OST in general practice reported high uptake of HCV screening (92.5%) [60]. A later 2007 multi-site study reported high levels of HCV screening among PWUD on MMT in Dublin based general practice (77%) [44]. Only a third of those infected had been screened for chronic infection (36%) [44].

Identified gaps
No studies reported on incidence infections specifically in prisoners, PWUD or PWID in general practice or not on OST and PWUD without a history of IDU. Only two studies reported on HCV prevalence in PWUD outside of Dublin and both where from secondary urban centres. The majority of the prevalence studies are over a decade old and only report on anti-HCV prevalence and not on HCV-RNA prevalence which limits their usefulness at estimating the levels of chronic untreated infection and reinfection. The most recent epidemiological studies included in this review are mostly chart review audits which limit their usefulness to inform policy and strategy.

Guidelines and policy (8 studies)
A total of 8 documents were identified that fitted into this category. The first published national document relating to HCV infection in PWUD and prisoners was published in 2004 [66]. This was a regional (Dublinbased) document that reported on the views of 70 stakeholders (service planners, funders, providers and users)   on a broad range of HCV related issues including policy and clinical issues [66]. In the same year, a research lead initiative developed consensus guidelines on HCV management in general practice [67]. The effectiveness of these guidelines was later evaluated in a cluster randomised trial and were found to improve the uptake of screening in practices where the policy was implemented (OR = 3.76 CI = 1.3-11.3) [56].
The National Hepatitis C Strategy 2011-2014 was the first published strategy relating to all those infected with HCV in Ireland [14]. The strategy spans surveillance, prevention, screening and treatment of HCV infection and reports on both groups (PWUD and prisoners). The Department of Health (DOH) subsequently published a report: A Public Health Plan for the Therapeutic Treatment of Hepatitis C in 2015 which recommended the establishment of the National Hepatitis C Treatment Programme (NHCTP) in the HSE [68].
The NHCTP was established in 2014 and oversees treatment provision to all HCV infected patients in Ireland, including PWUD and prisoners [26]. This program has a number of specialist committees that advise on the treatment criteria and guidelines and also includes a treatment register which collects data on treatment uptake and outcomes.
The HSE developed national HCV screening guidelines to identify HCV-infected individuals who are currently unaware of their HCV status [10]. These guidelines were preceded by two opioid substitution guidelines that contained recommendations on the screening of drug users on OST [69].
The Irish Prison Services are responsible for the provision of health care in all prisons in the ROI and in parallel to community-based guidelines have further sets of guidelines that deal specifically with HCV management within the IPS [70]. The provision of all healthcare, including HCV treatment is guided by the international principle of community equivalence of care [71].
The major gap identified in this category is that the national strategy was published pre-DAA and no longer reflects the reality of HCV treatment in particular the challenges related to moving HCV treatment from hospital services to the community. The new national HCV screening guidelines provides a clear road map on who to screen but to date there is not data on the success of their implementation. It is also important that the IPS update their health care standards in line with the new national screening guidelines and NHCTP to ensure community equivalence (Table 3).

Treatment outcomes (13 studies)
A number of papers reported on treatment uptake and outcomes. These studies found poor engagement with hepatology services for liver assessment and treatment by PWUD [43,44,55,60,63,73]. Predictors for poor treatment follow up were, younger age, active IDU and advanced HIV disease, male gender [74,75]. A single prison study reported that no HCV infected prisoner on MMT was on HCV treatment at the time of the study [57].
In-reach hepatology services provided HCV treatment at two Dublin based prison location. An audit of these sites shows high compliance with treatment and good treatment outcomes [78].
A single study reported on the use of tele-medicine as a novel approach to increasing treatment among HCV infected PWUD attending MMT. This study showed high levels of satisfaction among professionals engaging with the initiative [79].
A number of gaps in the treatment outcome literature were identified including: the lack of SVR outcomes for DAA treatment, re-infection rates and treatment uptake and completion rates. There are no mathematical modelling studies conducted using existing surveillance data and treatment uptake and outcomes to map pathways towards HCV elimination in Ireland (Table 4).

HCV -related health issues (8 studies)
A number of studies reported on HCV related health issues. Two hospital-based studies found higher levels of depression and anxiety among HCV infected patients whose risk factor for acquisition was IDU [80,81].
A 2003 mathematical modelling study estimating the national HCV-related disease burden over 20 years, predicted 1214 cases of cirrhosis, 35 cases of HCC, 60 cases of hepatic decompensation and 50 cases of liver related deaths per annum [49].
A number of papers describe high levels of alcohol use among HCV infected PWUD (41%) [40,62,63]. Studies report high levels of HCV-related liver disease and awareness that excessive alcohol had a negative impact on HCV disease progression among PWUD on OST [62,73] [40].
A 25 year follow up study of PWID attending general practice found high levels of mortality in a cohort with HCV exposure having a negative impact on life expectancy (O' Kelly & O'Kelly, 2012). A unique five-year follow up study among PWUD attending OST showed high mortality rates of among patients with high Fibroscan scores which was associated with heavy alcohol use. The study concluded that a single Fibroscan score was highly predictive of mortality (McCormick et al., 2014).  Overall the research on HCV related health issues was considered to be scant and incomplete. While a number of studies report on levels of liver disease in small groups of PWUD on OST, the literature does not provide a clear picture of the HCV disease burden in these two groups. In the early days of DAA treatment HCV infected patients with advanced liver disease were prioritised for treatment access but it is unclear how many of these accessed or completed treatment. There is also no published data on the numbers of HCV infected PWUD who die annually from non-HCV related causes. This may be considerable given the high levels of drug related deaths in Ireland and if not accurately quantified will have an impact on Irish HCV elimination strategies (Table 5).

Qualitative research reporting on patients' and health providers' experiences
A number of studies report a high awareness of HCV infection among PWUD on OST both in primary care and drug treatment centres [40,43]. This includes the knowledge that IDU is a major risk factor for transmission among this group and the health implications of being infected [43]. There were also high levels of awareness of patients own HCV status, of HCV harm reduction measures, and adverse effects alcohol has on the progression of HCV liver disease [40,43].
A prison-based study exploring the health needs of female prisoners using focus group methodology reported that HCV infection was identified as a health concern among Irish female prisoners [25].
A number of studies identified barriers to PWUD engagement in HCV treatment including; ongoing alcohol and drug use, fear of HCV treatment and liver biopsy, imprisonment, distance to hospital, early morning appointments, perceptions of HCV infection as relatively benign, fear of investigations and treatment including liver biopsy and interferon, feeling well, limited knowledge of testing sites, not being referred for specialist investigations, ineligibility for treatment and competing priorities (employment, education, and addiction) [43,73,79,83]. Some of these studies reported on enablers to PWUD engagement which included; afternoon appointments, enhanced prison referral mechanisms into the community, community fibroscanning, location of services within the addiction treatment services, relationships with health care providers, trust in providers, concern for the service-user, continuity of care, education on HCV infection, investigations, and treatment, becoming symptomatic, responsibilities for children, wanting to move on from drug use [73,83].
Only two studies reported on healthcare professionals' experience of providing care to HCV infected prisoners and PWUD. A single prison study reported lack of knowledge regarding BBVs including HCV had a negative impact on prison officers' work [85]. A recent study identified lack of time and inadequate funding as barriers to community GPs engaging with HCV treatment [79].
As previously identified the major deficit in this category is that it reports from a pre-DAA era. This is particularly relevant for barriers to treatment engagement which was related to the fear and experience of side effects of interferon-based treatments. There is a need to conduct more up to date quantitative research on PWUD S′ and prisoners' experience of the HCV treatment cascade with DAA treatments. This can best inform the planning of effective HCV delivery systems ( Table 6).

Discussion
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.   One-to-one in-depth interviews Multiple layers of stigma were reported, linked to sex work, drug use (including IDU) and having contracted HIV or HCV • Stigma was powerfully reinforced by the language routinely used by health professionals.
• To improve the effectiveness of harmreduction interventions, it is recommended that service providers change their language, in particular in recognition of the human dignity of these clients, but also to help attract and retain drug users in services, and to help reduce the unacceptable mortality levels among drug users. Patient identified barriers to engagement: • alcohol and drug use • fear of HCV treatment and liver biopsy

• imprisonment
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 prisonbased 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 • PWID were identified as the main group facing barriers to accessing specialist HCV care.
• State-employed doctors and nurses were successfully recruited to participate in the project.
• GPs did not participate, due mainly to a lack of time and the absence of reimbursement for participation.
• Benefits to practitioners and their patients were reported. Participants expressed interest in continued engagement with similar multidisciplinary, multisite educational interventions in the future.
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.

Conclusion
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.