Susceptibility to Hepatitis B Virus Infection Among People Who Inject Drugs in Montreal, Canada
Funding: This work was supported by Canadian Institutes of Health Research (190788).
ABSTRACT
Introduction
People who inject drugs are at elevated risk of hepatitis B virus (HBV) infection, which is preventable by vaccination. We examined susceptibility to HBV infection among a sample of people who inject drugs and live in Montreal, Canada.
Methods
Data were obtained from HEPCO, a prospective cohort study of people who had recently (within the past six months) injected drugs, between November 2022 and March 2024. The absence of hepatitis B surface antibody indicated susceptibility to HBV infection. These results were compared to self-report immune status. Logistic regression was used to identify factors associated with HBV susceptibility.
Results
Overall, 28.1% (108/384) of participants were susceptible to HBV infection. Over half (60.2%, 231/384) of participants correctly reported their immune status. Individuals born in Canada prior to the introduction of universal childhood vaccination programs had higher odds of susceptibility to HBV infection (adjusted odds ratio: 2.63, 95% confidence interval: 1.34–5.61), while those in opioid agonist treatment (0.60, 0.37–0.98) and with a history of hepatitis C infection (0.51, 0.32–0.83) had lower odds of HBV susceptibility.
Discussion and Conclusions
An important minority of people who inject drugs in Montreal remain susceptible to HBV infection. Moderate concordance between self-report and serological results indicates that serology or vaccine registry information should continue to be used to inform immunisation provision. People who inject drugs who were born prior to childhood vaccination programs and/or are not in opioid agonist treatment are subpopulations who require targeted interventions to increase vaccination coverage.
1 Introduction
Although universal childhood vaccination programs have reduced hepatitis B incidence globally, prevalence among people who inject drugs remains high [1]. Hepatitis C prevalence among this population is also high [2], increasing the risk of hepatitis B/C co-infection, which is associated with more severe negative health outcomes [3]. Maximising vaccination coverage among this population is crucial to achieve the World Health Organization's goal to reduce new hepatitis B infections by 90% and deaths by 65% between 2016 and 2030.
Hepatitis B vaccination is recommended for people who inject drugs in the Canadian Immunisation Guide [4] and funded for this population in Québec [5]. However, people who inject drugs typically have suboptimal vaccination coverage [6]. Barriers to vaccination differ by vaccine and setting, but a recent US paper described competing priorities (e.g., locating stable housing) and the need for multiple vaccine doses as barriers to hepatitis B vaccination among this population [7]. Injecting drug use was associated with acute hepatitis B infections diagnosed between 1990 and 2015 in British Columbia, suggesting that current vaccination coverage is insufficient to completely prevent transmission among this population [8].
Measuring the proportion of a population who remain susceptible to HBV infection can provide important information to policymakers about the effectiveness of a vaccination program. In 2005, 96% of a sample of people who inject drugs in Montreal reported hepatitis B vaccination [9]. However, self-report has poor validity [10] and HBV infection confers immunity against further infection, so the vaccinated population is a subset of the immune population. This is a key consideration for a population in which transmission is known to occur. Serology can be used to measure both vaccine- and infection-induced immunity and mitigates issues associated with self-report.
In this study, we used both serological and survey data from a cohort of people who inject drugs in Montreal to: (i) determine susceptibility to hepatitis B virus; (ii) compare immune status using serological data to self-reported vaccination and infection; and (iii) identify sociodemographic factors associated with susceptibility.
2 Methods
2.1 Setting and Study Design
Data came from HEPCO, a prospective cohort study established in 2004 that follows people who actively inject drugs in Montreal, Canada [11]. Participants are recruited via a combination of street-level strategies and community referral. People are eligible for the study if they are aged ≥ 18 years, report injecting drug use in the six months prior to screening, and reside in the Montreal area. Participants at risk of primary or recurrent hepatitis C virus infection are followed up every three months; those with chronic hepatitis C virus infection are followed up annually. Participants who report ≥ 24 consecutive months of no injecting drug use become ineligible for follow-up as they are no longer considered part of the target population (people actively injecting drugs).
Hepatitis B surface antibody (HBsAb) has been measured among HEPCO participants since November 2022. Participants whose serology indicated they were susceptible to infection were vaccinated by research staff or referred to immunisation services. This was a cross-sectional study using data from participants' first interview between 29 November 2022 and 22 March 2024 in which hepatitis B serology results were available.
2.2 Ethical Approval
Ethical clearance for the study was obtained through the institutional review board of the Centre de recherche du Centre hospitalier de l'Université de Montréal. Participants provided informed consent at enrolment and were remunerated 40 CAD for their time.
2.3 Measures
For aim 1, HBsAb was measured in participants' venous blood samples. Individuals with a titre ≥ 10 mIU/mL were considered immune and therefore not susceptible to hepatitis B. Those with a nonreactive titre (< 10 mIU/mL) were considered susceptible to infection. HBsAb results do not distinguish between vaccination- and infection-induced immunity.
For aim 2, we used participants' responses to survey questions on prior vaccination (receipt of either standard hepatitis B vaccination or combination hepatitis A/B vaccination) and hepatitis B diagnosis to assess concordance between self-reported and serologically confirmed susceptibility to HBV. We constructed a four-level self-report indicator for HBV susceptibility: (i) unknown (responded ‘don't know’ regarding both vaccination and infection or ‘don't know’ to one and ‘no’ to the other); (ii) susceptible (neither vaccinated nor infected); (iii) immune due to infection (including people who reported both infection and vaccination); and (iv) immune due to vaccination (any number of doses).
For aim 3, we analysed the association between HBV susceptibility and the following sociodemographic characteristics. We considered eligibility for the Québec universal childhood vaccination program [4], with participants considered either eligible (born in Canada in 1985 or later or moved to Canada in 1985 or later at an age they were still eligible for vaccination); ineligible because they were born in Canada prior to 1985; or ineligible because they were born outside of Canada. The decision to split the ineligible group by country of birth was motivated by the higher prevalence of hepatitis B infection in foreign-born Canadian residents [8], although some participants born outside of Canada might have been eligible for vaccination in their country of birth. Participants reported the ethnic group they most identified with, which was categorised as White; Aboriginal, Inuit or Métis; or other. Small numbers necessitated the latter umbrella category. Participants also reported their gender identity (woman/female; man/male; non-binary/queer/other), recent (i.e., past three months) accommodation (stable [living in own/friend's/family's house/apartment, mid/long term accommodation]; unstable [prison, hotel/motel, boarding house, health facility, psychiatric facility], or street/shelter), recent (i.e., past three months) opioid agonist treatment (OAT; yes/no), and incarceration (never; yes > three months ago; yes ≤ three months ago). The latter two variables were included as they are settings where vaccination or referral to vaccination is known to occur [12-14]. Participants reported which drugs they had ever injected and the age at which they first injected them. This information was used to ascertain the duration since injecting drug use initiation (categorised as ≤ 5 years and > 5 years). Hepatitis C antibody, indicative of lifetime exposure to hepatitis C virus, was detected using enzyme immunoassay.
2.4 Analysis
We assessed the association between hepatitis B susceptibility and sociodemographic and health characteristics using the Chi-squared test. Variables associated with the outcome at p < 0.05 were included in a multivariable logistic regression model. Concordance between self-report and serology immune status was reported descriptively.
Analyses were conducted in R (version 4.3.1).
3 Results
Since November 2022, 418 participants completed at least one interview. Of these, 91.9% (384/418) had valid hepatitis B serology data and were included for analysis. Sociodemographic and health characteristics were similar between included and excluded participants, except more men were retained for analysis (Table A1). Among the sample for analysis, most identified as men (82.3%), were ineligible for the Canadian childhood hepatitis B vaccination (i.e., born prior to 1985 or born outside of Canada; 80.5%), and first injected drugs more than five years ago (85.9%; Table 1). Almost half had recently been prescribed OAT (44.5%).
| All participants, n (%) | % susceptible to hepatitis B virus, (n/N) | p | aOR (95% CI) a | |
|---|---|---|---|---|
| Total | 384 (100.0) | 28.1% (108/384) | — | — |
| Eligibility for Canadian universal childhood vaccination program | ||||
| Eligible | 72 (18.8) | 15.3% (11/72) | 0.023 | 1 |
| Ineligible, born in Canada prior to 1985 | 286 (74.5) | 31.1% (89/286) | 2.63 (1.34, 5.61) | |
| Ineligible, born outside of Canada | 23 (6.0) | 30.4% (7/23) | 1.66 (0.50, 5.24) | |
| Missing | 3 (0.8) | |||
| Gender | ||||
| Man/male | 316 (82.3) | 29.1% (92/316) | 0.691 | / |
| Woman/female | 57 (14.8) | 24.6% (14/57) | ||
| Nonbinary, queer or other gender identity | 7 (1.8) | 14.3% (1/7) | ||
| Missing | 4 (1.0) | |||
| Ethnicity | ||||
| White | 335 (87.2) | 29.0% (97/335) | 0.409 | / |
| Aboriginal, Inuit or Métis | 16 (4.2) | 12.5% (2/16) | ||
| Other | 33 (8.6) | 27.3% (9/33) | ||
| Missing | 0 (0) | |||
| Housing b | ||||
| Stable | 205 (53.4) | 25.9% (53/205) | 0.551 | / |
| Unstable | 24 (6.2) | 29.2% (7/24) | ||
| Street or shelter | 154 (40.1) | 31.2% (48/154) | ||
| Missing | 1 (0.3) | |||
| Incarceration | ||||
| Never | 106 (27.6) | 34.0% (36/106) | 0.212 | / |
| Yes, > 3 months ago | 242 (63.0) | 26.0% (63/242) | ||
| Yes, ≤ 3 months ago | 33 (8.6) | 21.2% (7/33) | ||
| Missing | 3 (0.8) | |||
| Opioid agonist treatment b | ||||
| No | 210 (54.7) | 34.3% (72/210) | 0.005 | 1 |
| Yes | 171 (44.5) | 21.1% (36/171) | 0.58 (0.35, 0.94) | |
| Missing | 3 (0.8) | |||
| Hepatitis C antibody status | ||||
| Negative | 155 (40.4) | 35.5% (55/155) | 0.005 | 1 |
| Positive | 222 (57.8) | 22.1% (49/222) | 0.50 (0.30, 0.81) | |
| Missing | 7 (1.8) | |||
| Duration of injecting drug use | ||||
| ≤ 5 years | 52 (13.5) | 32.7% (17/52) | 0.508 | / |
| 330 (85.9) | 27.6% (91/330) | |||
| Missing | 2 (0.5) | |||
- Abbreviations: aOR, adjusted odds ratio; CI, confidence interval.
- a Variables associated with the outcome at p < 0.05 were included in the multivariable model.
- b In the past 3 months.
In total, 28.1% (108/384) were susceptible to hepatitis B virus infection. Overall, 60.2% (231/384) of participants had concordant self-reported and serological immune status (Table 2). After excluding those who said they did not know, 73.8% (231/313) had concordant results. The majority of those who reported being vaccinated (80.0%, 191/240) or infected (73.3%, 11/15) had serological evidence for hepatitis B immunity. Half of those who reported neither vaccination nor infection were susceptible to infection (50.0%, 29/58).
| Serology | Total | |||
|---|---|---|---|---|
| Immune | Susceptible | |||
| Self-report | Immune due to vaccination a | 191 | 49 | 240 |
| Immune due to infection b | 11 | 4 | 15 | |
| Susceptible (neither vaccinated nor infected) | 29 | 29 | 58 | |
| Unknown c | 38 | 21 | 59 | |
| Missing | 7 | 5 | 12 | |
| Total | 276 | 108 | 384 | |
- Note: Concordant results are bolded.
- a Includes individuals who reported being vaccinated with the standard hepatitis B vaccine and/or combination hepatitis A/B vaccine.
- b Includes 9 individuals who reported being both infected and vaccinated.
- c Includes individuals who responded ‘don't know’ to infection and vaccination questions and those who responded ‘don't know’ to one and ‘no’ to the alternate.
Participants born in Canada prior to the introduction of vaccination programs had higher odds of HBV susceptibility compared to those born since programes were introduced (adjusted odds ratio: 2.63, 95% confidence interval: 1.34–5.61; Table 1). Participants recently prescribed OAT (0.58, 0.35–0.94) and hepatitis C antibody positive (0.50, 0.30–0.81) had lower odds of HBV susceptibility.
4 Discussion
Among this sample of people who inject drugs in Montreal, approximately one third were susceptible to HBV infection. This appears to be similar to the Canadian adult population (30% not vaccinated [15]), a recent sample of people receiving community-based hepatitis C treatment in the US who inject drugs (35% susceptible [16]), and two community samples of people who inject drugs recruited in Australia over a decade ago (26.5%–45% susceptible [17, 18]). Just over half the sample accurately reported their immune status to HBV. Participants born in Canada prior to the introduction of universal childhood vaccination programs had higher odds of susceptibility to infection, while those currently in OAT and with a history of hepatitis C infection had lower odds.
Despite recommendations that people who inject drugs receive hepatitis B vaccination, a minority of this sample remain susceptible to HBV infection. The gap in coverage may be a result of multilevel barriers this population experiences to non-emergency healthcare [19]. Service providers have noted that vaccine hesitancy is a key barrier to providing hepatitis B vaccination to this population [7]. Information on specific drivers of hepatitis B vaccine hesitancy is lacking, but multiple studies have investigated COVID-19 vaccine hesitancy and found that low risk perception of disease, vaccine misinformation, and institutional distrust contribute to lower intention to be vaccinated [20-23]. The association with birth cohort suggests that coverage will be higher among new cohorts of people who inject drugs. However, the continued role of injecting drug use in HBV transmission in Canada means it is critical to maximise vaccination coverage among those currently injecting drugs and susceptible to infection [24].
Provision of hepatitis B immunisation services at low threshold settings (e.g., needle syringe programs) has improved uptake [25]. Our finding that 40% of participants did not accurately report their HBV status supports previous advice to offer vaccination to all individuals without evidence of immunity [26]. Offering screening in parallel with the first vaccine dose is a cost-effective strategy to prevent new infections [26] and ensures that existing undiagnosed cases are linked to care [27]. In traditional health settings, a barrier to free hepatitis B vaccination is the requirement to disclose injecting drug use (or other risk factor) which can be associated with stigma and discrimination. In the US, immunisation policy was recently updated to recommend universal adult hepatitis B vaccination, meaning injecting drug use no longer needs to be disclosed, which may improve uptake among this group [28]. Given the gap in coverage despite vaccination policy recommendations, targeted efforts to improve uptake among people who inject drugs are warranted.
Consistent with other studies of vaccine uptake among people who inject drugs [12, 29, 30], OAT was associated with decreased odds of susceptibility to HBV infection. Although we could not distinguish between vaccine- and infection-induced immunity, almost all participants whose serology indicated they were immune to infection reported vaccination rather than infection. OAT is consistently associated with more favourable health outcomes [31], likely in part due to contact with primary health services or community-based pharmacies. This reiterates the important role low-threshold services might play in referring people not in OAT to immunisation services. Encouragingly, people with a history of hepatitis C virus infection, who are at risk of more severe negative health outcomes if co-infected with hepatitis B, had lower odds of susceptibility to HBV infection. We found no evidence that incarceration was associated with lower HBV susceptibility, indicating a missed opportunity for vaccination. Given the overrepresentation of people who inject drugs in carceral settings, as well as high rates of tattooing [32], prisons could consider opt-out vaccination for non-immune people entering prison.
4.1 Limitations
The primary limitation of this study is that HBsAb titres may decline below the level of detection despite the individual being immune. Therefore, we may have overestimated the proportion of the sample susceptible to infection. Linkage with a vaccine registry, which Quebec introduced in 2019 to capture all subsequent vaccinations and any previous electronically recorded vaccinations, could mitigate this issue and provide a mechanism to routinely monitor coverage. This was a service-engaged sample recruited in a single city and may not be representative of the broader population of people in Canada who inject drugs.
5 Conclusion
Despite the inclusion of people who inject drugs in Canadian hepatitis B vaccination policy recommendations, approximately one-third of this sample were susceptible to HBV infection. Given evidence for continued transmission of HBV among this population, improving vaccination coverage is critical to Canada achieving the World Health Organization hepatitis elimination goals by 2030. People who inject drugs and were born prior to the introduction of universal childhood vaccination programs or who are not receiving OAT are particular subpopulations who warrant targeted immunisation delivery.
Author Contributions
All authors were involved in the conceptualisation and design of the study. O.P. conducted the analysis and drafted the manuscript. All authors were involved in critical review and editing of the manuscript.
Acknowledgements
Funding for this research was received via a CIHR catalyst grant (190788). O.P. is supported by postgraduate scholarships from the Australian National Health and Medical Research Council and National Drug and Alcohol Research Centre. V.M.L. is supported by Clinical Research Scholar – Junior 2 program (FRQ-S). B.H. is supported by Fonds de Recherche du Québec – Santé and CanHepC. J.B. holds the Canada Research Chair in Addiction Medicine. S.L. is supported by a Research Scholar award from Fonds de recherche du Québec. Open access publishing facilitated by University of New South Wales, as part of the Wiley - University of New South Wales agreement via the Council of Australian University Librarians.
Conflicts of Interest
S.L. has received advisory board fees from Gilead Sciences. J.B. has received advisory board fees from Gilead Sciences, AbbVie and Cepheid, and research grant from Gilead Sciences, outside the scope of this work. The remaining authors have no competing interests to declare.
Appendix A
| Included in HBV analysis, n (row %) | Excluded from HBV analysis, n (row %) | p | |
|---|---|---|---|
| Total | 384 (100) | 34 (100) | — |
| Eligibility for Canadian universal childhood vaccination program | |||
| Eligible | 72 (18.8) | 6 (17.6) | 0.952 |
| Ineligible, born in Canada prior to 1985 | 286 (74.5) | 25 (73.5) | |
| Ineligible, born outside of Canada | 23 (6.0) | 1 (2.9) | |
| Missing | 3 (0.8) | 2 (5.9) | |
| Gender | |||
| Man/male | 316 (82.3) | 22 (64.7) | 0.032 |
| Woman/female | 57 (14.8) | 9 (26.5) | |
| Non-binary, queer or other gender identity | 7 (1.8) | 2 (5.9) | |
| Missing | 4 (1.0) | 1 (2.9) | |
| Ethnicity | |||
| White | 335 (87.2) | 30 (88.2) | > 0.999 |
| Aboriginal, Inuit or Métis | 16 (4.2) | 1 (2.9) | |
| Other | 33 (8.6) | 3 (8.8) | |
| Missing | 0 (0) | 30 (88.2) | |
| Housing a | |||
| Stable | 205 (53.4) | 17 (50.0) | 0.955 |
| Unstable | 24 (6.2) | 2 (5.9) | |
| Street or shelter | 154 (40.1) | 14 (41.2) | |
| Missing | 1 (0.3) | 1 (2.9) | |
| Incarceration | |||
| Never | 106 (27.6) | 8 (23.5) | 0.910 |
| Yes, > 3 months ago | 242 (63.0) | 19 (55.9) | |
| Yes, ≤ 3 months ago | 33 (8.6) | 3 (8.8) | |
| Missing | 3 (0.8) | 4 (11.8) | |
| Opioid agonist treatment a | |||
| No | 210 (54.7) | 13 (38.2) | 0.197 |
| Yes | 171 (44.5) | 18 (52.9) | |
| Missing | 3 (0.8) | 3 (8.8) | |
| Hepatitis C antibody status | |||
| Negative | 155 (40.4) | 6 (17.6) | 0.202 |
| Positive | 222 (57.8) | 17 (50.0) | |
| Missing | 7 (1.8) | 11 (32.4) | |
| Duration of injecting drug use | |||
| < 5 years | 52 (13.5) | 3 (8.8) | 0.599 |
| ≥ 5 years | 330 (85.9) | 31 (91.2) | |
| Missing | 2 (0.5) | 0 (0) |
- a In the past 3 months.
Open Research
Data Availability Statement
Research data are not shared.
