Background and Objectives
Hepatitis C virus (HCV) infection is a major public health issue. There is substandard uptake in HCV assessment and treatment among people who inject drugs (PWID). Community fibroscanning is used to assess disease severity and target treatment.
A survey was administered to a cohort of chronically HCV infected patients attending a community fibroscanning clinic. Questions targeted diagnosis of HCV, suitability, willingness and barriers to engagement in treatment. Descriptive and regression analysis, with thematic analysis of open-ended data was conducted.
There was high acceptance of community fibroscanning among this cohort with over 90% (68) attending. High levels of unemployment (90%) and homelessness (40%) were identified. Most patients were on methadone treatment and had been HCV infected for greater than 10 years with length of time since HCV diagnosis being significantly longer in patients with fibroscan scores > 8.5 kPa (P = 0.016). With each unit increase in methadone dose, the odds of the >8.5 fibroscan group increased by 5.2%. Patient identified barriers to engagement were alcohol and drug use, fear of HCV treatment and liver biopsy, imprisonment, distance to hospital and early morning appointments.
The study highlights the usefulness of community fibroscanning. Identifying barriers to treatment in this cohort affords an opportunity to increase the treatment uptake. The availability of afternoon clinics and enhanced prison linkage are warranted.
Hepatitis C virus (HCV) infection remains a major public health burden. It is spread by contact with infected blood or other bodily fluids.[1-6] An estimated 185 million people are infected with HCV globally with a reported 15 million Europeans living with HCV infection.[8, 9] Chronic disease outcomes occur in 55-85% of untreated cases, and center around an impaired quality of life, liver cirrhosis, liver failure and hepatocellular carcinoma.[10, 11] Injecting drug use remains a significant driver of the European HCV epidemic with estimates that HCV antibody prevalence among persons who inject drugs (PWID) in 29 European countries ranges from 5% to 90% with growing rates of HCV among new injectors of novel psychoactive substances (NPS).[8,12-13]
There is a high prevalence of HCV within the aging PWID population, characterized by many undiagnosed cases and failure to access treatment Surveillance and monitoring of HCV in Europe, particularly regarding levels of antiviral treatment uptake among PWID are limited.[15-17] Recent increases in HCV infection among PWID in some European countries are reported despite increased efforts to upscale the HCV cascade of care.[18,19]
Low rates of HCV treatment uptake and sub-optimal access are reported among PWID.[6,9,20-22] PWID encounter significant barriers to accessing the HCV treatment[15,23] and are often denied treatment due to concerns around the on-going risk behavior despite treatment reducing further transmission.[6, 23, 24] HCV treatment outcomes in PWID are comparable to general population patients with no history of drug use.[23,25-27] Despite suboptimal access and uptake, research demonstrates a PWID interest in HCV treatment.[28-32]
Up to recently, the standard treatment for chronic HCV infection was pegylated interferon (PEG-IFN) and ribavirin (RBV). The development of new drug therapies includes protease and polymerase inhibitors (DAAs) that are well tolerated, do not require liver biopsy and have minimal side effects. Liver biopsy whilst evident as the gold standard of liver fibrosis is difficult, invasive and costly. Liver stiffness measurement (LSM) using fibroscan is increasingly being used to assess disease severity. This procedure can help to enhance HCV assessment, reduce treatment barriers, triage patients and target therapy.[14, 36] Several studies have reported on the feasibility of fibroscanning as a screening tool for drug users, with high rates of acceptance and uptake within various treatment and street outreach settings.[37-41]
In Ireland, an estimated 20,000-50,000 people have been exposed to HCV infection, giving a prevalence rate of 1-2%. Most recent prevalence data of HCV in the Irish PWID population ranges from 62-81%[42, 43] with risk factors similar to those reported elsewhere. These are injecting drug use,[42, 43-47] frequency and length of time injecting,[45, 48, 49] needle sharing and having a history of imprisonment. Low uptake of screening and follow up assessments are also reported[51-53] In Ireland, the treatment with DAAs is restricted to those with more advanced liver disease, determined by fibroscan score, with current guidelines identifying those with scores of > 8.5 kPa as being eligible for the treatment.
The aim of the study was to report on characteristics of OST patients attending a community based fibroscanning clinic, and their reported barriers to engaging with HVC treatment in Ireland. The fibroscanning clinic took place in The City Clinic, the largest community based drug treatment center in Ireland. This center provides OST to 300 opioid dependent patients living in the North inner city area of Dublin, an area of social deprivation. Patients entering OST are offered viral screening within a month of starting the treatment and post a risk behavior thereafter. A viral screen audit was completed to identify patients with chronic HCV infection, who had not successfully completed the HCV treatment in the past and who would benefit from an assessment by fibroscan (n=80).
The data collection tool was designed based on consultation with the literature and team review. The instrument contained a series of descriptive questions collecting data on gender, age, employment status, dose and length of time on methadone, length of time since/location of HCV diagnosis, if referred/attended hospital for follow up, if ever had a biopsy and if previously offered / completed HCV treatment. Patients were asked a series of open ended questions around HCV symptoms experienced, self-reported drug and alcohol stability, reasons for non-attendance, factors contributing to non-attendance and potential facilitators for treatment engagement.
Ethical approval was given by The Mater Hospital, Dublin, Ireland as part of the European HepCare Project. Patients were given an information sheet on the study and provided written consent. The questionnaire was administered by a research assistant who accompanied the nurse specialist performing the fibroscan.
Anonymized data yielded descriptive statistics (frequencies, percentages) to summarize the participant characteristics. Statistical tests using SPSS including the Chi square tests, t-tests and P-values were used to assess the differences in categorical data, with a significance level of 0.05. Multinominal logistic regression analysis was used to determine predictors of answer responses with the neutral response category as the reference. Qualitative open ended comment data were thematically coded for common and emergent themes using QSR–NVIVO-10.
The mean age of the participants was 39 years with no significant difference between men and women. A high proportion of patients described their accommodation as not stable (40%) and only 9% were engaged in some form of employment. The average methadone dose was 75 mL with an average of 10 years on MMT (Table 1) with again no difference between men and women. The majority of participants (71%) self-declared ongoing/drug or alcohol instability as a factor impacting their ability to engage with the HCV assessment and treatment.
Population characteristics by gender
|Total (n=68)||Male (n = 50)||Female (n= 18)||P-Value|
|Age (years)||39.0 (35.2, 44.0)||40.0 (35.0, 45.0)||39.0 (35.7, 42.0)||0.882|
|Accommodation status stable % (n)||61.7 (42)||58.0 (29)||72.2 (13)||0.366|
|Engaged in work % (n)||8.8 (6)||6.0 (3)||16.6 (3)||0.201|
|Time on MMT (years)||10.0 (5.0, 19.5)||10.0 (5.0, 19.2)||12.5 (6.2, 19.5)||0.773|
|Methadone dose (mL)||75.0 (47.0, 90.0)||75.0 (50.0, 90.0)||70.0 (43.7, 90.0)||0.251|
|Alcohol /drug unstable (self-declared) % (n)||70.5 (48)||70.0 (35)||72.2 (13)||0.913|
On an average, the study population was diagnosed with Hepatitis C for 10.5 years, with just less than half (47%) describing having symptoms related to HCV infection. Over half the group (57%) had previously been offered a hospital appointment for HCV follow-up with most attending (54%). Less than a third (27%) of the group had a previous liver biopsy or fibroscan. Of this group, only thirteen patients had been assessed as suitable for treatment with significantly more men than women being told they were suitable for interferon based treatment (26% vs. 0%; P=0.016) (Table 2), but none of these had been engaged.
Population characteristics by HCV issues and gender
|Total (n=68)||Male (n= 50)||Female (n = 18)||P-Value|
|Diagnosed hepatitis C (years)||10.5 (8.0, 16.2)||10.0 (7.7, 17.0)||12.5 (9.0, 6.7)||0.817|
|Symptoms related to hepatitis C % (n)||47.0 (32)||42.0 (21)||61.1 (11)||0.172|
|Offered OPD appointment % (n)||57.3 (39)||60.0 (30)||50.0 (9)||0.414|
|Attend OPD appointment % (n)||54.4 (37)||54.0 (27)||55.5 (10)||0.906|
|Previous liver biopsy or Fibroscan % (n)||29.4 (20)||32.0 (16)||22.2 (4)||0.348|
|Fibroscan result (kPa)||6.4 (5.2, 10.1)||7.2 (5.3, 11.8)||5.6 (5.2, 6.7)||0.104|
|Previously assessed suitable for treatment % (n)||19.1 (13)||26.0 (13)||0||0.016|
|Fibroscan result >8.55 (kPa) % (n)||32.3 (22)||38.0 (19)||16.6 (3)||0.072|
|Fibroscan result >12.5 (kPa) % (n)||20.3 (12)||20.0 (10)||11.1 (2)||0.362|
Fibro scan score population characteristics (>8.5 kPa)
|Fibro scan score|
|<8.5 (n=37)||>8.5 (n=22)||P-Value|
|Age (years)||39.0 (35.0, 42.5)||40.0 (36.0, 45.2)||0.339|
|Accommodation status stable %(n)||64.8 (24)||59.0 (13)||0.404|
|Engaged in work %(n)||8.1 (3)||9.0 (2)||0.965|
|Time on MMT (years)||10.0 (5.0, 17.0)||10.0 (2.0, 20.0)||0.921|
|Methadone dose (mL)||60.0 (40.0, 82.5)||80.0 (63.7, 95.0)||0.072|
|Diagnosed hepatitis C (years)||10.0 (6.0, 15.0)||15.0 (8.5, 20.0)||0.016|
|Having symptoms related to hepatitis C (self-declared) % (n)||43.2 (16)||50.0 (11)||0.513|
|Alcohol /drug unstable (self-declared) % (n)||67.5 (25)||77.2 (17)||0.941|
Fibro scan score population characteristics (>12.5 kPa)
|Fibro scan score|
|<12.5 (n=47)||>12.5 (n=12)||P-Value|
|Age (years)||39.0 (35.0, 43.0)||40.5 (36.0, 46.0)||0.301|
|Accommodation status stable % (n)||59.5 (28)||75.0 (9)||0.584|
|Engaged in work % (n)||10.6 (5)||0 (0)||0.170|
|Time on MMT (years)||10.0 (4.2, 15.2)||20.0 (9.2, 25.0)||0.179|
|Methadone dose (mL)||65.0 (45.0, 80.0)||90.0 (72.5, 98.7)||0.091|
|Diagnosed hepatitis C (years)||10.0 (7.0, 15.0)||17.0 (14.0, 20.0)||0.012|
|Having symptoms related to Hepatitis C (self-declared) % (n)||40.4 (19)||66.6 (8)||0.244|
|Alcohol /drug unstable (self-declared) % (n)||72.3 (34)||66.6 (8)||0.294|
The average Fibro scan score was 6.4 kPa. Almost a third of this cohort had Fibro scan sore > 8.5 kPa, with a slightly higher proportion of men (38%) compared to women (16.6%) reaching this score but this failed to reach statistical significance (P=0.072). Over 20% of patients had a fibroscan score of > 12.5 kPa. Importantly, there was no significant difference between patients experiencing selfdeclared HCV related symptoms and their fibroscan score [> 8.5 (P=0.5) (Table 3), > 12.5 kPa (P=0.2) (Table 4)]. Participants with a Fibro scan score > 8.5 kPa were diagnosed with having Hepatitis C for a significantly longer period than those with a san score < 8.5 kPa (15 years vs. 10 years, P = 0.016, Table 3). Homelessness, employment status, length of time on MMT, patients experiencing HCV related symptoms and self-declared drug and alcohol stability seemed to have no impact on a patient having a fibro scan score > 8.5 kPa and being eligible for treatment with DAAs in Ireland. Of particular interest is that with each unit increase in methadone dose, the odds of being in the > 8.5 Fibroscan group increased by 5.2 % (Table 5)
Predictor’s of fibroscan scores
|Unstandardized coefficients||95% Confidence interval|
|Methadone dose (mL)||0.16||0.08||0.049||0.00||0.31|
|Years diagnosed Hepatitis C (years)||0.21||0.32||0.506||-0.43||0.85|
HCV symptoms experienced
A majority of participants (70%) self-reported drug instability. Participants reported use of excess alcohol, smoking of opiates and crack cocaine and use of benzodiazepines, with a minority reporting continued IDU of heroin. A minority reported daily or problematic use of alcohol. HCV symptoms experienced included abdominal pain, stomach bloating, fatigue, anxiety, weight gain, swelling of the limbs and a yellow tinge to the skin (Table 5). Some participants were not aware of any HCV symptoms. A majority of those with fibroscan scores of > 8.5 kPa were not aware of HCV symptoms other than fatigue (Beta = 0.051, Exp (B) = 1.052, P = 0.026, 95% CI (1.006-1.1).
Barriers to attendance
Individual patient reasons for not initially attending the HCV clinic centered around on-going drug and alcohol use, on-going injecting drug use, not wanting to have treatment at the time, fear around invasive HCV and treatment interventions and addiction treatment relapse. Many narratives illustrated lack of readiness for treatment of HCV. One participant described being too ill from interferon to attend the clinic. Of particular note were the significant barriers reported by those with a fibroscan score of > 8.5 kPa, which centered on the inability to engage with HCV treatment and care due to custodial sentencing, poor prison referrals, parental bereavement and chaotic family and drug using lifestyles. Many participants also described chaotic personal and family lifestyles, and lengthy distance from the clinic making treatment adherence and attendance at early appointments difficult to commit to.
Enablers to treatment
When questioned about the facilitators to ensure continued engagement with HCV treatment, participants described structural barriers that included problems when no follow-up appointments were kept. This may have been due to clinic staff concern around chaotic lifestyles and on-going drug and injecting drug use, or appointments provided and not attended. Afternoon appointments, enhanced prison referral mechanisms into the community fibroscanning unit, and the location of services within the addiction treatment and detoxification services were viewed as potentially useful.
The study presented a unique Irish profile of OST patients accessing a community based fibro-scanning clinic in Dublin, Ireland. The participants in this study reflect an aging cohort of PWIDs with a mean age of 39 years, with high levels of unemployment (> 90%) and homelessness (40%) on long term MMT (> 10 years) and having a diagnosis of untreated chronic HCV infection for over a decade. A majority of patients (n = 70%) described the ongoing issues of drug and alcohol instability that impacted their ability to engage with HCV services. This group was traditionally seen as hard to reach group for engagement with health services and in particular with HCV screening, assessment and treatment.[9,14,21-23] This study shows that when screening and fibro scanning are offered at drug treatment locations, patients will engage in these services (n= 85%).
The average fibro scan score in this cohort was 6.4 kPa, which is similar to that found in other studies.[39,41] Just under a third of participants had scores > 8.5 kPa (30%) indicating at least moderate fibrosis and eligible for DAAs in accordance with Irish HCV treatment criteria. 20% of the cohort had a score > 12.5 kPa, indicative of cirrhosis. Of interest is that self-declared HCV related symptoms were no different in those with normal scores (< 8.5 kPa) compared to those with scores indicative of fibrosis (> 8.5 kPa) and cirrhosis (> 12.5 kPa). This is an important finding showing that patients may not be aware of the severity of their liver disease and may have developed significant levels of fibrosis and cirrhosis before these are identified by treatment services. It may also reflect the high levels of other disease morbidities seen in this group along with symptoms of drug and alcohol withdrawals that may mask symptoms of chronic HCV infection.
As expected, the patients with scores > 8.5 kPa were diagnosed with HCV significantly longer than those with a scores < 8.5 kPa (P=0.16). This reflects the progression of liver disease over time after HCV exposure. Contrary to what might be expected, the impact of self-declared drug and alcohol instability did not have a significant impact on fibroscan score. Ongoing alcohol misuse in chronically HCV infected individuals is associated with more severe liver disease. Separating drug and alcohol stability as risks may have yielded a different result, but this finding is in keeping with poly-drug use pattern of this cohort and the tendency to substitute alcohol and illicit drug use over a lifetime of addiction and drug abuse. The high levels of self-declared drug and alcohol stability are also of interest. Despite patients receiving therapeutic doses of methadone maintenance treatment (MMT, average dose 75mL) for long periods of time (>10 years) 70% indicated that drug / alcohol instability affected their ability to engage with HCV services. This may reflect the level of social exclusion (90% unemployment) of this group and supports the provision of augmented rehabilitation and support services to this marginalized group.
A unique finding of this study was that with each unit increase in methadone dose, the odds of being in the > 8.5 Fibroscan group increased by 5.2%. To our knowledge, this has not been previously reported. This may indicate that the patients requiring higher doses of methadone are at greater risk of developing more severe liver disease and can potentially be used to target higher risk groups among PWIDs for HCV treatment interventions.
Previous studies have illustrated how barriers to effective HCV care among Irish PWID center on negative experiences at diagnosis, investigations and treatment Findings in this study described patient reluctance to engage with HCV assessment due to ongoing alcohol and drug use, injecting drug use, OST treatment relapse, fear around HCV and invasive treatment interventions and inability to attend due to custodial sentencing and lack of prison referral. Barriers to continued engagement centered on illness, distance from the treatment setting, early appointments and lack of follow up appointments, potentially due to staff concerns around on-going drug and alcohol use, or provided and not attended. Individual barriers to accessing HCV care reported elsewhere center on perceptions that HCV is a harmless disease or knowing someone who has died of HCV, absence of symptoms, fear of liver biopsy and standard treatment side effects (such as depression, fatigue, anxiety, anemia, fatigue, nausea, insomnia and flu like symptoms, and more rarely mania, psychosis and suicide), and the hospital setting with its logistical aspects, lengthy referral and waiting times, inflexible appointment systems and limited psychosocial supports.[14,21,36,54-56] Of particular note were the significant barriers to treatment engagement reported by those with a fibroscan score of > 8.5 kPa and eligible for DAA treatment, which centered on the inability to engage with HCV treatment and care due to custodial sentencing, parental bereavement, and chaotic family and drug using lifestyles. A majority of participants in this study with fibroscan scores of > 8.5 kPa were not aware of HCV symptoms other than fatigue, and continued to struggle with drug and alcohol abuse.
Structural factors affecting access relate to stigma, social and family support, housing, income, gender and criminalization. The participants in this study had very high level of unemployment (> 90%) and homelessness (40%) reflecting high levels of social deprivation and barriers that need to be addressed to improve HCV treatment uptake. These challenges underpin the clear need to continually target PWID for HCV screening and treatment, particularly using non-invasive methods such as Fibroscanning and expand methadone treatment services to include housing and employment/training interventions within community drug treatment settings.
Willingness to start HCV treatment in PWID generally ranges between 53-86%.[29, 30, 32, 57] While this study did not include data on the numbers who subsequently engaged with HCV treatment, it does show that when HCV assessment services are provided locally in community drug treatment clinics, the patients are willing and able to engage. An 80% uptake of fibro scan among this cohort is a very positive finding, particularly since over half had previously been referred and attended one hospital appointment but failed to follow up for assessment and treatment. Providing on site HCV treatment with DAAs could further impact on treatment uptake.
Assessment facilitators include becoming symptomatic, knowing HCV infection can cause liver disease and desire to be treated for this virus.[21, 36] Modifiable barriers at this individual patient level include lack of priority and knowledge, financial resources and fear of side effects Zickmund and colleagues, in their study of patients receiving opioid agonist therapy, described poor relations with health providers, lack of access to health care and antiviral therapies as the central barriers occurring despite intense educational efforts. Patients in this study described negative structural aspects of HCV services, which include lack of follow-up appointments and early appointments difficult to attend to due to distances, and family issues. Studies elsewhere report that patient negative views are also strongly influenced by peer networks and poor mental health. Peer support groups are increasingly utilized to increase engagement in the HCV cascade of care, and enhance patient knowledge.[59-60]
The barriers can be reduced by developing integrated care pathways, and incorporating HCV treatment and care within the community drug treatment services.[14, 15] Studies elsewhere emphasize the need to support and train nurses, general practitioners and addiction specialists in their key role in screening and PWID for HCV assessment and counselling.[14, 36] OST can underpin such HCV care pathways. Findings from this study underpin the usefulness of provision of community fibroscanning in providing community-based treatment for “vulnerable populations” such as PWID with the new DAAs, and particularly when situated within drug treatment services. Afternoon clinics and enhanced prison referral systems are warranted.
The strengths of this study include the selection of a particularly hard to reach group of HCV chronically infected PWIDs, a cohort that need to be studied to inform how HCV assessment and treatment uptake can be improved. It is the first study in Ireland to specifically target the chronically infected PWIDs and to identify their characteristics, to assess the extent of liver disease, the numbers requiring treatment in accordance with present national HCV treatment guidelines and to explore patient identified barriers and enablers to HCV treatment. The single site location of this study reduces it generalizability.
PWID are a high-risk and high-prevalence population for HCV infection.[12, 61] Although HCV treatment is effective for PWID,[21, 62] the uptake is lower than other risk groups.[29, 63-66] Offering HCV non-invasive fibroscanning within drug treatment services can identify and target those with chronic HCV, coupled with the potential positive outcomes when engaging in OST. Self-declared HCV related symptoms are not a reliable indicator of the level of liver disease and outreach fibroscanning offers an ideal opportunity to identify patients with more advanced liver disease including cirrhosis that are eligible for DAAs. Similar barriers and enablers to HCV treatment were described by this Irish cohort of PWID as previously described in previous studies, including drug and alcohol stability, injecting drug use, fear of HCV treatment and liver biopsy, imprisonment, chaotic life style, social exclusion and stigma. Uniquely, this study found a link with methadone dose and higher fibroscan scores, a finding which requires further research. Findings are intended to inform HepCare Europe in their development of a community based model of care in order to engage with PWID who are affected and infected with HCV.
Conflict of Interest All authors declare no conflict of interest.
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