Birth cohort hepatitis C antibody prevalence in real-world screening settings in Ontario

Abstract

Background

Widespread screening and treatment of hepatitis C virus (HCV) is required to decrease late-stage liver disease and liver cancer. Clinical practice guidelines and Canadian Task Force on Preventative Health Care recommendations differ on the value of one-time birth cohort (1945–75) HCV screening in Canada. To assess the utility of this approach, we conducted a real-world analysis of HCV antibody (Ab) prevalence among birth cohort individuals seen in different clinical contexts.

Methods

Cross-sectional study of individuals born between 1945 and 1975 who completed HCV Ab testing at multiple participating centres in Ontario, Canada between January 2016 and December 2020. Differences in prevalence were compared by year of birth, gender, and setting.

Results

Among 16,672 birth cohort individuals tested, HCV Ab prevalence was 3.2%. Prevalence was higher among younger individuals which increased from 0.9% among those born between 1945 and 1956 to 4.6% among those born between 1966 and 1975. Prevalence was higher among males (4.4%) compared with females (2.0%) and differed by test site. In primary care, the prevalence was 0.5%, whereas the prevalence was highest among those tested at drug treatment centres (28.7%) and through community outreach (14.0%).

Conclusions

HCV Ab prevalence remains high in the 1945–1975 birth cohort. These data highlight the need to re-evaluate existing Canadian Preventative Task Force recommendations, to consider incorporating one-time birth cohort and/or other population-based approaches to HCV screening into the clinical workflow as a preventative health measure, and to increase training among community providers to screen for and treat HCV.

Introduction

In 2016, the World Health Organization (WHO) set a goal of eliminating hepatitis C virus (HCV) as a global health threat by 2030 (1). This is possible because of improved diagnostic testing, and perhaps more importantly, the widespread availability of well-tolerated, all-oral antiviral therapy with cure rates of over 95%. Along with many other countries, Canada has committed to achieving the WHO targets. However, to reach elimination, identifying those with undiagnosed HCV will require widespread community-based testing. The United States was first to adopt the one-time birth cohort screening, after it was found that 45% of individuals had no known risk factors, and perhaps more importantly, there was a lack of provider knowledge and time to properly screen for risk factors (2). As a result, the Centres for Disease Control and Prevention (CDC) recommended one-time “baby boomer” or birth cohort screening among individuals born between 1945 and 1965 without prior ascertainment of HCV risk (2). More recently, based on changing epidemiology, the CDC has updated their guidance to recommend one-time HCV testing for all adults and all pregnant women (3,4).

HCV also disproportionately affects baby boomers in Canada. However, Canada has been slower to adopt one-time birth cohort screening. Data suggest that one-time birth cohort screening would capture 77% of HCV-infected individuals living in Canada (reviewed by (5)) which is particularly relevant given that up to 70% of these individuals are unaware of their infection (6,7). In Canada, expanding one-time birth cohort screening to include individuals born between 1965 and 1975 would identify a higher proportion of HCV infections (8). A regional study in Ontario anonymously tested 10,006 serum samples for the presence of HCV antibodies and determined that seroprevalence was 1.6% among those born between 1945 and 1974 (9). Furthermore, recent data from the BC Testers Cohort showed that this cohort represented most infections (10). Birth cohort screening is also predicted to be highly cost-effective in Canada (11,12).

At present, the Canadian Association for the Study of the Liver (CASL) recommends one-time birth cohort screening as a part of the updated guideline on the management of chronic hepatitis C, published in 2018 (13). However, in 2017, the Canadian Task Force for Preventive Health Care recommended against screening for those who did not have risk factors. The major rationale for the Task Force recommendation was concern that access to treatment may be limited due to the high cost of therapy (14). The CASL guideline committee noted that the Canadian Task Force may have overestimated the potential harms of screening and the costs of treatment, while undervaluing the benefits of curative therapy (13). Importantly, as of 2018, individuals with chronic HCV infection are eligible for publicly funded treatment, irrespective of liver disease severity, in every province and territory, addressing the access concern raised by the Task Force. We aimed to conduct a real-world analysis of HCV antibody (Ab) prevalence among a large cohort of individuals born between 1945 and 1975 tested in a variety of clinical settings in Ontario, Canada to further characterize the prevalence of HCV within the birth cohort.

Methods

HCV Ab screening was conducted in multiple settings across Ontario, Canada between January 2016, and December 2020. HCV Ab testing occurred by conventional serologic laboratory testing, the OraQuick® HCV Rapid Antibody Test, or a dried blood spot collection card. Follow-up HCV RNA testing after a positive antibody test was site specific. Deidentified data were entered into a standardized case report form by each centre and sent to the central site, the Toronto Viral Hepatitis Care Network (VIRCAN) at the Toronto Centre for Liver Disease (University Health Network, Canada).

Study population and variables

Individuals born between 1945 and 1975 who completed HCV Ab testing at a participating centre or community setting were included. Centres were categorized based on setting and patient population served as follows: primary care, screening event, community outreach, drug treatment centres (all substances), emergency department (ED), walk-in clinic, and other. Primary care included Family Health Teams, Community Health Centres, Nurse Practitioner-Led Clinics, and solo/team family medicine physician practices. Screening events were defined as one-time events such as health fairs, screening events held in hospital lobbies, etc. Community outreach was characterized as screening events for higher-risk individuals in organizations such as shelters, drop-ins, etc. on multiple occasions at a certain frequency. Drug treatment centres included Ontario Addiction Treatment Centres, rapid access addiction medicine clinics, and drug recovery and rehabilitation centres. The “other” category included pharmacies, sexual health clinics, and HIV pre-exposure prophylaxis (PrEP) clinics. Demographic data included age at the time of testing and gender either by self-identification or chart reported. Data related to testing included the date of the HCV Ab test and the test result. The primary outcomes analyzed in this study was HCV Ab positivity by year of birth, gender, and setting.

Statistical analysis

Characteristics of the study cohort were presented as frequency and proportions for categorical variables, and as mean ± SD for continuous variables. Between-group comparisons used Chi-squared testing or t-test, as appropriate. Logistic regression was used to analyze the association between HCV Ab positivity and year of birth, gender, and type of centre. We also tested for interactions between covariates. Significant interactions were entered into a multivariable model. Predicted probabilities of a positive test result were calculated after multivariable logistic regression. A two tailed p-value < 0.05 was considered statistically significant. Statistical analyses utilized STATA version 15.0 (StataCorp, College Station, TX). The collection of these data has received a Research Ethics Board Waiver from University Health Network (17-0136).

Results

Screening

There were 16,672 HCV Ab tests conducted between January 2016 and December 2020 among individuals within the birth cohort. Mean age at the time of testing was 57.6 ± 8.2 years, and 51.1% of those tested were women (n = 8,523) (Table 1). Those tested were sub-divided by decade within the birth cohort: 26% born between 1945 and 1955 (n = 4,329), 37.5% (n = 6,259) born between 1956 and 1965, and 36.5% born between 1966 and 1975 (n = 6,084). Most of the testing occurred in primary care settings (54.2%, 9,034) however, considerable testing also occurred via screening events (10.9%, 1,818), community outreach (11.3%, 1,887), and at EDs (10.9%, 2,368).

Table 1:

Characteristics of birth cohort who completed HCV Ab testing

Total HCV Ab tests, N	16,672
Age at test, years, mean ± SD	57.6 ± 8.2
Year of birth, no. (%)
1945–1955	4,329 (26.0)
1956–1965	6,259 (37.5)
1966–1975	6,084 (36.5)
Chart-reported gender, no. (%)
Women	8,523 (51.1)
Men	8,149 (48.9)
Type of centre, no. (%)
Primary care	9,034 (54.2)
Emergency department	2,368 (14.2)
Walk-In clinic	963 (5.8)
Screening event	1,818 (10.9)
Community outreach	1,887 (11.3)
Drug treatment centre	471 (2.8)
Other	131 (0.8)

HCV Ab positivity

Among those screened, overall HCV Ab positivity was 3.2% (529) (Table 2). On univariate analyses, there were significant differences in the proportion of positive results by year of birth, gender, and type of testing centre (p < 0.001 for all) (Table 2). There were also significant interactions between year of birth and gender (p < 0.001), year of birth and type of centre (p = 0.02), and gender and type of centre (p = 0.04) on regression analyses.

Table 2:

Univariate analyses for an HCV Ab positive test result

	HCV Ab positive		Logistic regression
	no. (%) or mean ± SD	Chi-squared p-value	Crude odds ratio (95% CI)	p-value
Total	529 (3.2)
Age at test, years	54.3 ± 6.5	< 0.001*	0.95 (0.94–0.96)	< 0.001
Year of birth†
1945–1955	39 (0.9)	< 0.001	1.00 (reference)
1956–1965	210 (3.4)		3.82 (2.71–5.39)	< 0.001
1966–1975	280 (4.6)		5.31 (3.79–7.44)	< 0.001
Chart-reported gender
Women	171 (2.0)	< 0.001	1.00 (reference)
Men	358 (4.4)		2.24 (1.87–2.70)	< 0.001
Type of centre‡
Primary care	45 (0.5)	< 0.001	1.00 (reference)
Emergency department	47 (2.0)		4.05 (2.68–6.10)	< 0.001
Walk-In clinic	7 (0.7)		1.46 (0.66–3.25)	0.35
Screening event	26 (1.4)		2.90 (1.78–4.71)	< 0.001
Community outreach	265 (14.0)		32.6 (23.7–45.0)	< 0.001
Drug treatment centre	135 (28.7)		80.3 (56.3–114.4)	< 0.001
Other	4 (3.1)		6.29 (2.23–17.8)	0.001

* t-test was used

† Year of birth: 1956–1965 versus 1966–1975, p < 0.001

‡ Type of centre: Emergency department versus walk-in clinic, p = 0.01; emergency department versus screening event, p = 0.18; walk-in clinic versus screening event, p = 0.11

HCV Ab positivity by year of birth

The proportion of positive results was lowest among individuals born between 1945 and 1955 (0.9%, 39) and increased among the subsequent 10-year intervals, 3.4% among those born between 1956 and 1965 (210), and 4.6% among those born between 1966 and 1975 (280) (Table 2).

HCV Ab positivity by gender and year of birth

The proportion of positive results was higher among men (4.4%, 358) compared with women (2.0%, 171) (Table 2). Among women, the proportion of positive results by year of birth ranged from 0.4% for those born between 1945 and 1955 (9) to 3.7% for those born between 1966 and 1975 (108) (Figure 1). Among men, the proportion of positive results by year of birth ranged from 1.5% for those born between 1945 and 1955 (30) to 5.5% for those born between 1966 and 1975 (172). Thus, for both genders recorded, the proportion of positive results was higher among younger individuals.

Figure 1:

Proportion of HCV Ab positive test results by year of birth and gender

HCV = Hepatitis C virus; Ab = Antibody

HCV Ab positivity by testing site, year of birth, and gender

The proportion of positive results was highest among tests conducted at drug treatment centres (28.7%, 135) and through community outreach (14.0%, 265), compared with other types of testing centres (Table 2). However, greater than 1% of tests were positive at EDs (2.0%, 47), through screening events (1.4%, 26) as well as in other settings (3.1%, 4). HCV Ab positivity was 0.5% in primary care settings (45), and 0.7% at walk-in clinics (7).

The association of age within the birth cohort and HCV positivity differed by testing setting. The percent positivity was highest among individuals born between 1956 and 1965 in primary care (0.7% positive, 22) and EDs (3.5% positive, 29), whereas in most other settings the highest proportion positive was seen in those born between 1966 and 1975: 2.8% at screening events (16), 16.6% through community outreach (144), and 31.4% at drug treatment centres (88) (Figure 2A). When stratified by gender, HCV Ab positivity was higher among men under all settings except at walk-in clinics (Figure 2B).

Figure 2:

Proportion of HCV Ab positive test results within each type of centre by A) year of birth, and B) gender

HCV = Hepatitis C virus; Ab = Antibody

Even though younger individuals and men generally had higher percent HCV Ab positivity, the relationship between gender and HCV Ab positivity differed by site and age group. In primary care settings, men born between 1956 and 1965 had the highest percent positivity (1.3%) however, at EDs, the percent positivity was similar between men and women (3.4% versus 3.5%) in that age group. In community settings, the percent positivity was higher in younger patients (born between 1966 and 1975) but similar between men and women (Figure 3).

Figure 3:

Proportion of HCV Ab positive test results and adjusted predicted probabilities by year of birth and gender within each type of centre

HCV = Hepatitis C virus; Ab = Antibody

Discussion

Our study highlights that there are differences in HCV Ab positivity by age, gender, and clinical setting among the 1945–1975 birth-cohort. Overall, HCV Ab positivity among those born between 1945 and 1975 in settings such as such drug treatment centres or community outreach was high; and even EDs, walk-in clinics, and primary care led to case-finding.

Although we did not have the ability to specifically look at prevalence among people who inject drugs (PWID), our data are in line with other estimates of an overall high prevalence in drug treatment; however, these studies vary based on country, screening strategies, and reporting. For example, a recent report by the European Monitoring Centre for Drugs and Drug Addiction assessed 13 European countries where HCV prevalence ranged from 15%–84% (15), similar to the variation in prevalence in Canadian studies (16,17). Rates among PWIDs have likely increased during the COVID-19 pandemic. In Ontario, a 25% increase in opioid-related deaths occurred in comparison to the same months in 2019 (18). The positivity found in our study of 29% in drug treatment centres certainly supports universal screening in addictions clinics, rehabilitation, or recovery centres. In addition to the benefit for the individual, identifying people with ongoing risk factors may also have a prevention benefit provided linkage to care and treatment is achieved, which then prevents transmission.

Community outreach included shelters, drop-ins, street outreach, and other similar settings, where individuals may have current or past high-risk activity where they have acquired HCV. The community outreach within our dataset was high yield for screening with 14% positivity. Community outreach could be conducted by clinicians, other types of service providers, or peers/those with lived experience, either with HCV or with similar life experiences. Although difficult to define, increasing community outreach and meeting people where they are spending their time (eg, shelter, drop-ins, homeless encampments, overdose prevention sites, etc.) yield a high prevalence and provides a location where the individual could be met for follow-up.

Our birth cohort screening prevalence in the ED was 2.0%. Although not a standard approach to screen patients for HCV in Canada when they are seeking care in the EDs, multiple studies in the US have demonstrated the value of screening at hospital EDs, including during COVID-19. A study of four large urban emergency centres in the US used opt-out testing to screen 14,252 individuals for HCV antibodies, yielding a prevalence of 13.9% among the baby boomer cohort (1945–1965) (19), in line with other US studies (20). Perhaps a more striking finding was the benefit to screening all adults in these settings; with a prevalence of 5%–6% (19,20). We have recently demonstrated that using inputs from our Toronto screening program presented here, ED screening is cost-effective (21). In this context, it is important to note that screening in the ED may be a supplemental approach to achieve wide birth cohort screening, as patients who attend the ED may face challenges seeking routine primary care or may not have a primary care provider.

Of note, a prevalence of 0.5% in primary care in our data represents the population who seek primary care, and who complete testing; and may not reflect a true prevalence that would be found in primary care if universal screening of birth cohort was routine. For example, perhaps individuals who screened positive in settings with high positivity rates in our study would have been identified earlier, if universal screening in primary care occurred. Of those who do seek regular primary care, universal screening among the birth cohort is especially important, as their HCV risk factor and acquisition is more likely to be many years or decades ago, putting them at higher risk for cirrhosis, liver failure, or liver cancer. Thus, prioritizing testing and treatment to prevent advanced liver disease is an important public health consideration.

Acknowledging barriers to implementing birth cohort screening for HCV is important. Although we have shown the value of screening in other settings, primary care has traditionally been seen as the medical home or hub for patients. This includes offering preventative health care such as routine screening for cancer. In the United States, studies demonstrate that providers were aware of the birth cohort screening recommendations, but major barriers existed in terms of competing clinical priorities, time to discuss HCV, comfort level with risk assessment, and screening fatigue (22–25). Targeting primary care providers is especially important in the context of HCV, as primary care providers can directly link patients to care and treat those who are positive in their practice (reviewed by (26)). To overcome these barriers, innovative evidence-based approaches require wide implementation in Canada. Such approaches include online education for providers, leaflets for providers and patients, mail outs, electronic medical record reminders/audit software for identification and redesigning nursing workflow (27–31). Other approaches should also be considered such as preventative health incentives to physicians for HCV screening, considering the disease burden of HCV among the birth cohort over the next 15 years (32).

Our data demonstrated that those born between 1966 and 1975 had higher rates than those born between 1945 and 1965. With the ongoing opioid epidemic in the United States, the CDC recently completed a literature review of available studies which may inform testing strategies. Although in 33 studies prevalence among baby boomers was 3.3%, overall, the prevalence among those 18 years and older was 6.6% (3). As a result of the high prevalence among 104 studies carried out in those over 18, the CDC and The US Preventative Task Force now recommends one-time HCV screening of all adults (3,4). Our data highlight the need for future studies to evaluate the prevalence among adults born after 1975 to determine if Canada should also consider screening all adults.

This study has limitations. This cohort includes the number of HCV tests conducted and may not uniquely identify individuals. Although this is a large screening cohort in Ontario, unlike the study by Bolotin et al, it does not equally represent age bands and regions (9). Additionally, these data only represent VIRCAN partner organizations, and may bias towards certain settings or practice types. Although the prevalence data suggest birth cohort testing would be useful, determining the preferred screening strategy would require prevalence data in other age cohorts as well as revised cost-effectiveness analyses to compare different approaches.

These real-world findings from Ontario support one-time birth cohort screening, certainly at locations where there may be more at-risk individuals, but also at EDs, and perhaps walk-in clinics/primary care. The overall HCV Ab positive prevalence among birth cohort individuals tested was 3.2%. HCV Ab positive prevalence varied by setting; with targeted community outreach for difficult-to-reach populations yielding a very high percent positivity. Our data also highlight the benefit of screening in primary care, walk-ins, and the ED; whereby widespread screening may identify large numbers of individuals. This comprehensive approach to effective screening, will be necessary to reach HCV elimination by 2030 in Canada, and to decrease overall morbidity and mortality related to HCV in the coming decades.

Acknowledgements:

This study could not have been completed without the assistance of the staff and volunteers at University Health Network and the extensive efforts of all VIRCAN’s community partners. We thank them for their commitment to hepatitis C elimination.

Ethics Approval:

The collection of these data has received a Research Ethics Board Waiver from University Health Network (17-0136).

Informed Consent:

N/A

Registry and the Registration No. of the Study/Trial:

N/A

Funding:

This study was supported by the Viral Hepatitis Care Network (VIRCAN), and made possible by through the support of Gilead Sciences Inc., AbbVie, Merck Canada Inc., and OraSure Technologies Inc./KNS Canada Inc. The funding sources did not have any influence on study design, data collection, analysis, and interpretation of the data, writing of the report nor the decision to submit for publication.

Disclosures:

MJ Biondi reports receiving research support and consulting fees from AbbVie, Gilead, and Specialty Rx Solutions. H Shah reports receiving consulting fees and research support from AbbVie and Gilead. JJ Feld reports receiving research support and consulting fees from AbbVie and Gilead. HLA Janssen reports receiving research support from AbbVie and Gilead. All other authors have nothing to disclose.

Peer Review:

This manuscript has been peer reviewed.

Animal Studies:

N/A