Health Reports
Hospitalization related to chronic hepatitis B and C in recent immigrants in Canada: An immigration administrative data-linked, population-based cohort study

by Edward Ng, Jacklyn Quinlan, George Giovinazzo, Maria Syoufi, Dominique Elien Massenat, Claudia Sanmartin and Curtis Cooper

DOI: https://www.doi.org/10.25318/82-003-x202200600003-eng

Abstract

Background

Canadian immigrants from countries where the hepatitis B virus (HBV) and hepatitis C virus (HCV) are endemic may be at higher risk of liver-related disease than Canadian-born residents. This study compared HBV- and HCV-related hospitalizations in Canadian immigrants (arriving from 1980 to 2013) and long-term residents (Canadian-born population and pre-1980 immigrants) and aimed to describe the burden of disease in both groups.

Methods

Based on the 2004/2005-to-2013/2014 hospital Discharge Abstract Database linked to the 1980-to-2013 Longitudinal Immigration Database, this descriptive cross-sectional study examined the distribution of HBV- and HCV-related hospitalizations, lengths of stay, comorbidities, and sequelae incurred by immigrants and long-term residents in Canada. With a linkage rate of 85%, 5,854,949 immigrants were included in the study. Proportions of HBV- and HCV-related hospitalizations attributable to immigrants were calculated.

Results

By birth country risk level, 22% of HBV-related hospital events among recent immigrants, and 20% of those related to HCV, were among people from high-risk countries. Proportionally, fewer immigrants had comorbidities than long-term residents. The top two hospital-related sequelae in both groups were cirrhosis and ascites, and liver cancer. While immigrants made up 16% of the Canadian population, they incurred 37% of HBV-related hospitalizations and 9% of HCV-related hospitalizations, giving ratios of hepatitis-related hospitalizations relative to the population share of 2.3 (95% confidence interval [CI]: 2.2 to 2.5) and 0.5 (95% CI: 0.5 to 0.6) respectively. These ratios were higher among seniors, at 4.4 (95% CI: 3.9 to 4.9) and 2.3 (95% CI: 1.9 to 2.6), respectively. 

Interpretation

Immigrants can require hospitalization for hepatitis in Canada, especially for HBV. These results may inform health screening for HBV or HCV in the Canadian immigration context.

Keywords

global health, health policy, infectious diseases, public health, statistics, and research methods

Authors

Edward Ng (edward.ng@statcan.gc.ca) and Claudia Sanmartin are with the Health Analysis Division, Statistics Canada. Jacklyn Quinlan, George Giovinazzo, Maria Syoufi and Dominique Elien Massenat are with the Migration Health Branch, Immigration, Refugees and Citizenship Canada. Curtis Cooper is with the Ottawa Hospital Research Institute.

Introduction

International commitments from the World Health Organization and the United Nations have prioritized the elimination of hepatitis.^{Note 1Note 2Note 3} Worldwide, 1% of the global population is infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV).^Note 4 The prevalence of HCV is highest in African and Asian countries,^Note 5 while that of HBV is highest in Sub-Saharan Africa; Oceania; and parts of Central Asia, East Asia and Southeast Asia.^Note 6 In Canada, an estimated 112,000 individuals are infected with HBV, and 220,000 with HCV.^{Note 7Note 8} Improving people’s awareness of their hepatitis status allows them to be better equipped to seek earlier care,^Note 9 and knowledge of their HBV or HCV status could improve the treatment and care of chronic viral hepatitis. Of those infected with HBV or HCV, more than half are unaware of their infection.^{Note 7Note 8} Chronic viral hepatitis can lead to significant morbidity and mortality,^Note 7 and it is estimated that 75% to 85% of HCV-infected individuals develop chronic disease.^Note 7 By contrast, the progression of HBV infection is age dependent, with 80% to 90% of HBV-infected infants developing chronic disease compared with 20% to 30% of HBV-infected adults.^Note 10 These infections are responsible for 80% of hepatocellular carcinoma cases^Note 11 and are major contributors to health care burden. In Canada, HCV is a leading cause for liver transplants among 35- to 59-year-olds.^{Note 12Note 13} Because of long asymptomatic latency periods, chronic HBV- and HCV-associated and liver-related sequelae are related to the duration of infection^{Note 4Note 14} and are often associated with older age. Immigrants from countries where HBV and HCV are endemic, while unaware, may be at a higher risk of infection and future liver-related hospitalization.^{Note 15Note 16Note 17}

Currently, Canada receives over 350,000 immigrants each year, with the numbers expected to grow. Patterns of migration have changed over time, with Asia and Africa now major source regions for immigrants to Canada.^Note 18 For admissibility purposes, Canada medically screens immigrants for selected diseases to mitigate the impacts on Canadian health and social services.^Note 19 Over the last several decades, immigration medical screening for HBV and HCV has included a medical history, questions on prior diagnosis and risk behaviour. Published studies show that there are various approaches to HBV and HCV screening to initiate care and mitigate the risk of clinical deterioration (e.g., HCV screening in immigrants from countries with a higher prevalence or screening by age-based cohorts and referrals if positive).^{Note 20Note 21Note 22} This descriptive study aims to characterize HBV- and HCV-related hospitalizations among immigrants compared with long-term Canadian residents.

Methods and data

Design and data sources

In this cross-sectional study, records from the hospital Discharge Abstract Database (DAD) were linked to the Immigrant Landing File (ILF) data at Statistics Canada, using previously described methods.^Note 23 Essentially, the Immigrant Landing File (ILF) data were linked to the DAD via a central depository called the Derived Record Depository (DRD) within the Social Data Linkage Environment (SDLE) at Statistics Canada. The DRD is a national dynamic relational database containing only basic personal identifiers, and was created by linking selected Statistics Canada source index files, including tax,birth and death data, to produce a list of unique individuals. The linkage was approved by Statistics Canada’s Executive Management Board,^Note 24 and the use and privacy of the data are governed by the Directive on Microdata Linkage.^Note 25

The DAD, from which the study population was constructed, contains demographic, administrative and clinical data for all acute care and some psychiatric, chronic rehabilitation, and day surgery discharges for all provinces excluding Quebec.^Note 26 Hospital discharges occurring between April 1, 1994, and March 31, 2015, were eligible for linkage in the present study (n=77,925,269 hospital discharge records). The linkage used a deterministic approach (linkage rate of 85%, n=66,246,909).^Note 27

The Longitudinal Immigration Database (IMDB), a research database representing unduplicated immigrant records derived from the ILF, was used to add recent immigrant status and other immigration-related characteristics to the DAD. At the time of this study, the latest available version of the ILF database contained immigration landing data up to the end of the 2013 calendar year. The ILF/IMDB contains administrative information for all individuals who have landed in Canada since 1980.^Note 28 In the present study, landing records between 1980 and 2013 were eligible for linkage (n=6,896,592 immigrants). Probabilistic methods were used to link the ILF/IMDB to the DRD (linkage rate of 85%, n=5,854, 949).

Outcomes

From the overall data linkage described above, the primary events observed in this study were HBV- or HCV-related hospital discharges occurring between April 1, 2004, and March 31, 2014. Hospital data from 2004 onward were used, since prior to 2004 HCV infection was not captured by all provinces in the International Classification of Diseases (ICD) coding. To characterize hospitalizations in immigrants, the final linked datasets were aligned, and thus information between April 1, 2004, and March 31, 2014, was included. 

Stratification variables

Age at hospitalization, derived as the difference between the DAD hospitalization year and the IMDB birth year, was grouped. Province of hospitalization from the DAD was grouped into regions: Atlantic (New Brunswick, Nova Scotia, Newfoundland and Labrador, and Prince Edward Island), Ontario, Prairies (Manitoba, Saskatchewan and Alberta) and British Columbia. Data from Quebec and the territories were not included in the analysis. Landing year and immigration class obtained from the IMDB were grouped. An individual’s birth country risk level was based on published HBV^Note 29 and HCV^Note 30 prevalence rates^{Note 31Note 32Note 33} (Appendix A).^{Note 29Note 30Note 31Note 32Note 33Note 34} Countries not assigned a risk level for HBV or HCV were coded as missing.

Statistical analysis

A two-step approach was adopted to identify HBV- and HCV-related hospitalizations.^Note 15 First, acute care hospital discharges with a primary diagnosis of a liver condition, related complications or liver transplantation were identified (Appendix B). Second, all additional diagnostic fields in each hospital record were scanned hierarchically for selected ICD-10 codes to classify these liver-related hospitalizations as being HBV- or HCV-positive (Appendix C). Sequelae and selected comorbidities of HBV or HCV were also identified (Appendix C). Among these hospitalizations, those linked to IMDB immigrants were classified as occurring among immigrants, and those that were not linked to the IMDB, but linked to the DRD, were classified as occurring among long-term residents (i.e., Canadian-born individuals and pre-1980 immigrants).

The distribution of HBV- or HCV-related hospital events was tabulated by selected characteristics for events and individuals for immigrants and long-term residents, separately. The distribution of major comorbidity and sequelae was examined. The distribution of HBV- or HCV-related hospital events was tabulated by selected characteristics for events and individuals for immigrants and long-term residents, separately. Counts were rounded up to the nearest 5 in accordance with Statistics Canada policy. To measure the burden of HBV- and HCV-related hospitalizations among immigrants compared with long-term residents, the mean and median of total days in hospital were calculated by selected individual characteristics. The total of days in the hospital was calculated by the difference between the admission date and the discharge date. 

The relative distribution of HBV- and HCV-related hospitalizations in immigrants was calculated as the ratio of hepatitis-related hospitalizations relative to the immigrants’ population share. This ratio was constructed as the percentage of HBV- and HCV-related hospitalizations occurring among immigrants over the estimated percentage of immigrants in the Canadian population, with the latter obtained from the 2011 National Household Survey (NHS).^Note 35 A ratio of more than 1 suggests that the relative burden of hospitalizations in immigrants was disproportionately more than its population share. Confidence intervals for the ratios were derived using a large sample approximation, and the variance estimates for the ratios are based on the Taylor linearization method,^Note 36 with the assumption that the numerators and denominators of the ratios are uncorrelated. Since potentially high-risk institutional populations in Canada were excluded in the Canadian-born population obtained from the 2011 NHS, but were included in the immigrant IMDB-linked data, a sensitivity analysis that increased the proportion of immigrants aged 65 years and older was conducted. 

Ethics approval

Research studies conducted at Statistics Canada do not require submission to an ethics board for approval. The record linkage was approved by Statistics Canada’s Executive Management Board^Note 24 and the data use is governed by the Directive on Microdata Linkage—public good, confidentiality and disclosure risk are assessed as part of this process.^Note 25 Participants’ privacy during record linkage and use of the linked files is ensured by Statistics Canada. Access to the unique identifying information (e.g., names) was limited to employees directly involved in linking the databases. They did not access the complete data files with information on individuals’ characteristics.

Results

Hepatitis B virus and hepatitis C virus acute care hospital events in Canada: Overall comparisons

Approximately 166,990 acute care hospital discharges (or 0.5%) between April 1, 2004, and March 31, 2014, were liver related (Figure 1). Among them, 4,810 (2.9%) were HBV related, and 20,870 (12.5%) were HCV related. After the non-links were removed, 37% (n=1,710) of HBV-related hospitalizations and 9% (n=1,770) of HCV-related hospitalizations were among immigrants (Figure 1). Although the total number of HCV events was more than four times higher than that for HBV, the numbers of HBV- and HCV-related hospitalizations among immigrants were similar (Figure 1). On average, each immigrant HBV patient was hospitalized 1.5 times over the follow-up period, similar to long-term residents (1.4 times), and this increased with age (Table 1). For HCV, the corresponding figure was 1.9 times for both immigrants and long-term residents. For both immigrants and long-term residents, HBV and HCV hospitalizations occurred predominantly within the 45 to 64 age group, and admissions occurred more commonly among males (Table 1). The overall mean length of stay for HBV- and HCV-related hospitalizations was 10 and 11 days, respectively. For HBV, immigrant females stayed longer on average than their male counterparts (12 vs. 9 days). For HCV, the mean hospital stays increased with age, especially among long-term residents.

Hepatitis B virus and hepatitis C virus acute care hospital events in Canada: Immigrant-specific comparisons

Among immigrants, 22% of HBV-related hospital events and 20% of those related to HCV were among those born in high-risk countries (Table 2). The highest proportion of HBV-related hospitalizations was among those from medium-risk countries (63%), and that of HCV-related hospitalizations from low-risk countries (34%). By immigration category, the highest proportion occurred among family class immigrants for both HBV (36%) and HCV (46%), followed by economic class principal applicants for HBV (25%) and by refugees for HCV (24%). Person-oriented results demonstrated similar findings. Among immigrants, for both HBV and HCV, minimal differences in mean hospital stay were observed by birth country risk level or immigrant class.

Comorbidity and sequelae distributions

Among those hospitalized for HBV and HCV, immigrants were less likely to have a comorbidity than long-term residents (Table 3). For immigrants with either HBV- or HCV-related hospitalization, the leading comorbid conditions were cardiovascular disease and type 2 diabetes, while alcohol-related conditions were more prevalent among long-term residents, especially those hospitalized with HCV-related conditions.

More than three-quarters of patients hospitalized for HBV and HCV had specific liver-related sequelae (Table 3). For HBV, the top sequelae among immigrants were primary liver cancer, at 52%, followed by cirrhosis and ascites, at 44%. That order was reversed among long-term residents, with cirrhosis and ascites at 53%, followed by liver cancer, at 32%. For HCV, the top sequelae were cirrhosis and ascites for both immigrants (67%) and long-term residents (68%), followed by primary liver cancer (35%) among immigrants and hepatic failure (24%) among long-term residents.

Hospitalizations related to hepatitis B virus and hepatitis C virus attributable to immigrants

Approximately 37% of HBV-related hospital events and 9% of those related to HCV occurred among immigrants, who represented 16% of the Canadian population (Table 4). This resulted in a ratio of 2.3 for HBV-related hospital events and 0.5 for HCV-related hospital events for immigrants. These ratios differed by age group, varying from 1.3 (for those aged 35 to 44 years) to 4.4 (for those aged 65 years and older) for HBV. In contrast, for HCV, ratios by age group never rose above 1, except for those aged 65 years and older (ratio of 2.3). A sensitivity analysis identified that the ratio for HCV among immigrants aged 65 years and older remained above 1 (1.9) when the population share for immigrants was increased from 9% (the proportion of immigrants who were aged 65 years and older in the 2011 NHS)^Note 35 to 11%.

Interpretation

This descriptive cross-sectional study of HBV- and HCV-related hospitalizations in Canada (excluding Quebec and the territories) demonstrates the usefulness of linking large administrative datasets to understand the extent to which immigrants experience serious health outcomes. This study focused on hospitalizations; while these events underrepresent the full spectrum of hepatitis, they are considered to be the most costly component of health care.^Note 37

Among immigrants, the highest proportions of HBV and HCV hospitalizations were among those from medium-risk and low-risk hepatitis countries, probably because of the high volume of immigrants arriving from countries such as China, India and the Philippines, a dominant trend in recent years.^Note 38 The distributions of comorbidities and sequelae of HBV- and HCV-related hospitalizations were similar between immigrants and long-term residents, except for the higher proportion of alcohol-related conditions among the latter.  

Our results corroborate those from other studies showing that, overall, immigrants are disproportionately represented among HBV patients^Note 39 in Canada but less so for HCV.^Note 40 As expected from an infection with a long subclinical phase, the proportion of hepatitis-related hospitalizations—especially for HCV—increased with age,^Note 38 and more than 40% occurred among immigrants who landed before 1993. In general, HCV is acquired at an older age than HBV.^{Note 4Note 10} Given the age and mechanism^Note 41 of acquisition, and the differences in disease expression related to comorbidities, HCV hospitalizations are expected to be higher in older age groups.^Note 42 This study found a higher distribution of HCV-related hospitalizations among immigrants relative to long-term residents in the group aged 65 years and older. This result may be because of an age-related cohort effect in which a lower burden of HCV among long-term residents in older age groups is associated with fewer hospitalizations as compared with younger long-term residents (i.e., born after 1950). This changes the ratio when compared with immigrants. This effect may be because of lower exposure to risk factors related to adverse outcomes (e.g., alcohol consumption) in the older long-term residents when compared with younger long-term residents. The higher alcohol-related comorbidity among long-term residents with HBV or HCV may account for the higher cirrhotic rate.^Note 12 A longer follow-up period may identify a higher ratio overall for HCV in immigrants.^Note 43 When HCV is managed at an early stage of the disease, it has a very high five-year survival rate (90% or more).^{Note 14Note 44} As direct-acting antivirals become more accessible worldwide—especially in Canada’s main source countries—the epidemiologic picture may shift since newer direct-acting antivirals have a prolonged sustained virologic response rate. 

Currently, the absence of a national standard for hepatitis testing practices can explain some of the regional differences in the distribution of hepatitis cases in relation to where immigrants reside. As well, all immigrants are medically screened upon entry to mitigate the impact on health and social services.^Note 19 Immigrants who could pose an excessive demand on these services may have failed the health admissibility criteria. Therefore, it is possible that immigrants who had advanced-stage hepatitis-related disease upon their application would not be admitted to Canada and would not be included in this study. The introduction of worldwide HBV vaccination at birth, coupled with the significant decreases in the cost for HCV treatment and the availability of inexpensive HBV treatment, will likely decrease future hospitalization rates for immigrants with known viral hepatitis. In addition, in 2018, changes were made to Canada’s medical admissibility criteria^Note 45 to better align with Canadian values on the inclusion of people with disabilities, while protecting publicly funded health and social services. These adjustments may lead to changes in immigrants’ admissibility, which could influence the epidemiology of HBV and HCV in Canada, as well as future hospitalization rates. One way to mitigate the impact on morbidity and future hospitalization rates would be to enhance HBV and HCV screening for early detection and treatment,^{Note 15Note 20Note 21Note 42} and implement a routine childhood HBV vaccination program. Hepatitis screening can improve the integration of individuals into health care systems as they relate to viral hepatitis,^Note 46 where clients are provided contacts to ensure continuity of care.^Note 47 To mitigate future hepatitis disease burden, initiatives such as testing, preventative measures (e.g., vaccination), public health education, early access to well tolerated and highly curative antiviral treatment (e.g., for HCV), disease counselling, and the provision of contacts for care have been proposed. Earlier identification and curative treatment could be cost-effective and beneficial for individuals.^{Note 48Note 49Note 50}

Limitations

Overall, immigrants are underrepresented in this study, since those who arrived before 1980 have not been classified as such and are instead identified as long-term residents. However, the incorporation of immigrants before 1980 into the long-term resident group would be unlikely to affect this study’s results since migration trends in Canada have changed over the past 100 years. Prior to the 1970s, European countries (i.e., the United Kingdom, Italy, Germany and the Netherlands) accounted for most of the immigrant source countries, with cultural and health risk profiles very similar to Canada’s population profile.^Note 35 The scope of this study was observational, therefore longitudinal factors affecting disease progression (e.g., time since diagnosis) were not available. Emigration data were not available, nor was it known whether immigrants still remained in the country; therefore, person-time at risk was not calculated. Also, since population denominators were unknown, it was not possible to perform age standardization. Thus, it is possible that the results could be confounded by age. This study may not reflect all hospitalizations among immigrants nationally since those from Quebec are excluded. The exclusion of data from the territories is unlikely to affect results because of the low immigrant population in this region. Hospitalization represents end-stage or severe disease and not the full disease spectrum, thus the burden of hepatitis is likely underrepresented in this study’s findings. Hepatitis-related hospitalizations generally occur after a long subclinical period. More hospitalization events may have been observed if a longer follow-up period was included. In addition, HCV and HBV country risk in this study is assigned using publicly available data, which are an approximation of the real risk level categorization for the timeframe of the study.^{Note 29Note 30Note 34}

The ratio to calculate HBV- and HCV-related hospitalizations attributable to immigrants could have been overestimated in this study, since institutional high-risk populations in Canada were excluded from the Canadian-born population obtained from the 2011 NHS data but were included in the immigrant IMDB-linked data. However, a sensitivity analysis showed that the ratio for HCV among immigrants who were most at risk, those aged 65 years and older, remained above 1 (1.9). If immigrants are less likely to access preventative and early care, this could lead to an increase in hospitalization rates among immigrants because of increasing severity over time.^Note 16 Furthermore, survivor selection bias, the bias that some immigrant patients might have died because of late detection, may result in an underestimation of the relative prevalence of HBV and HCV detected in immigrants.^Note 51 Additionally, the length of stay results could partially be a result of other factors, such as language proficiency or other barriers to care, resulting in difficulties for immigrants to interact with the health care system.^{Note 52Note 53} As a result, differences between immigrant and long-term residents must be considered when comparing both groups.

Conclusion

This study provides insights into HBV- and HCV-related hospitalizations incurred by immigrants using linked administrative immigration and hospital data. This additional information contributes to better understanding the health of this population. Developing and bolstering screening programs would help to identify those at risk of disease progression at earlier stages in order to prevent HCV-related complications, since there could be a high five-year survival rate (over 90%) when HCV is managed at an early stage.^Note 16 Existing literature^{Note 40Note 42} points to early detection, awareness and treatment that would have an impact on this population group as it ages and on health services. The use of health education may be one way to increase awareness among those who may be unaware of their infection.^{Note 54Note 55Note 56} The findings from this study point to the risks for this subpopulation and call for future studies, especially for HCV. Given that the recently updated IMDB includes immigrants who arrived in Canada from 1952 to 1979, a new linkage of the IMDB to more recent hospital data to extend the follow-up period would help ensure more comprehensive coverage of hospital events, in light of the long subclinical period of HBV and HCV.