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Twin epidemics of new and prevalent hepatitis C infections in Canada: BC Hepatitis Testers Cohort Janjua, Naveed Z; Yu, Amanda; Kuo, Margot; Alvarez, Maria; Cook, Darrel; Wong, Jason; Tyndall, Mark W; Krajden, Mel Jul 19, 2016

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RESEARCH ARTICLE Open AccessTwin epidemics of new and prevalenthepatitis C infections in Canada: BCHepatitis Testers CohortNaveed Zafar Janjua1,2*, Amanda Yu1, Margot Kuo1, Maria Alvarez1, Darrel Cook1, Jason Wong1,Mark W. Tyndall1,2 and Mel Krajden1,3AbstractBackground: We characterized the twin epidemics of new and prevalent hepatitis C virus (HCV) infections in BritishColumbia, Canada to inform prevention, care and treatment programs.Methods: The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV, HIV or reported as a caseof HBV, HCV, HIV or active TB between 1990–2013 linked with data on their medical visits, hospitalizations, cancers,prescription drugs and mortality. Prevalent infection was defined as being anti-HCV positive at first test. Those witha negative test followed by a positive test were considered seroconverters or new infections.Results: Of 1,132,855 individuals tested for HCV, 64,634 (5.8 %) were positive and an additional 3092 cases testedpositive elsewhere for a total of 67,726. Of 55,781 HCV positive individuals alive at the end of 2013, 7064 wereseroconverters while 48,717 had prevalent infection at diagnosis. The HCV positivity rate (11.2 %) was highest inbirth cohort 1945–1964 which declined over time. New infections were more likely to be male, 15–34 years of age(born 1965-1984), HIV- or HBV-coinfected, socioeconomically disadvantaged, have problematic drug and alcohol useand a mental health illness. The profile was similar for individuals with prevalent infection, except for lower odds ofHBV-coinfection, major mental health diagnoses and birth cohort >1975.Conclusions: The HCV positivity rate is highest in birth cohort 1945–1964 which represents most prevalentinfections. New infections occur in younger birth cohorts who are commonly coinfected with HIV and/or HBV,socioeconomically marginalized, and living with mental illness and addictions.Keywords: HCV, Hepatitis B, HIV, Epidemiology, Screening, Cohort studyBackgroundHepatitis C virus (HCV) is a major global publichealth problem. Worldwide, approximately 184 mil-lion people are infected [1], and in Canada, 210,753–461,517 (0.66 %-1.3 %) people are estimated to beinfected with HCV [2]. In British Columbia (BC), the an-nual rate of newly identified HCV cases is about 50 %higher than the national average [3]. Untreated HCVinfected individuals have a ~5-fold increased all-causeand ~20-fold increased risk of liver-related mortality[4]. While treatment reduces both morbidity andmortality, only about 10 % of infected individualshave been treated in BC [5]. Newer well-tolerated andhighly effective direct acting antiviral agents, withcure rate approaching 95 %, are expected to providenew opportunities to prevent progressive liver disease[6, 7]. However, a large number of people are unawareof their infection [2, 8]. Characterising individuals whohave been tested and who test positive can help identifyprevention, testing, care and treatment strategies andprograms to reach people most in need.In most developed countries, the different HCV affectedpopulations can be defined from their risk characteristicsthat can inform prevention, testing and treatment policies.HCV affected individuals could be classified into two* Correspondence: naveed.janjua@bccdc.ca1Clinical Prevention Services, British Columbia Centre for Disease Control,Vancouver, BC, Canada2School of Population and Public Health, University of British Columbia,Vancouver, BC, CanadaFull list of author information is available at the end of the article© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Janjua et al. BMC Infectious Diseases  (2016) 16:334 DOI 10.1186/s12879-016-1683-zbroad groups: prevalent and new infections. PrevalentHCV infections represent infections acquired in the dis-tant past and these individuals are usually not involved inongoing risk activities. New infections represent ongoingtransmission usually occurring in people with high riskactivities such as injection drug use. These two groups dif-fer not only in terms of demographics and risk factors butalso have varying levels of onward transmission risk andhence unique needs for engagement in prevention andcare. Characterization of these population groupsusing testing patterns, co-occurrence of other infec-tions (HIV, tuberculosis [TB], sexually transmitted in-fections [STIs], hepatitis B [HBV]), and social riskfactors (addiction and mental illness) could informthe design of prevention, testing and treatment pro-grams tailored to the specific needs of these groups.In this paper, we characterize twin epidemics of HCVinfection by describing characteristics and associatedfactors of acute and prevalent infections using datafrom the BC Hepatitis Testers Cohort (BC-HTC). Wefurther characterize the HCV disease burden by birthcohorts and present positivity by birth cohort to in-form birth cohort screening.MethodsThe cohort and study populationThe BC Hepatitis Testers Cohort(BC-HTC) includesall individuals tested for HCV or HIV at the BC PublicHealth Laboratory or reported to public health as aconfirmed case of HCV, HBV, HIV/AIDS or active TB.The cohort is linked with medical visits, hospitaliza-tions, prescription drugs, cancers and deaths [9–13](Table 1). Details of the cohort creation, linkage andcharacteristics of matched and unmatched individualshave been reported previously [14]. The overall link-age rate for HCV was >85 % and approached 90 %after 2006.BC-HTC participants with at least one HCV test (anti-body, HCV RNA, or genotype) or HCV case reportcontributed to the analysis from their first HCV test date(beginning 1992) or report (beginning 1990) throughdate of death or December 31, 2013, whichever wasearliest (Table 1). We excluded data which preceded aparticipants’ birth date or occurred >7 days after thedeath date. Antibody tests in infants <18 months in theabsence of HCV RNA testing were excluded as passivematernal antibody could not be ruled out.Table 1 Criteria and Data Sources for the BC Hepatitis Testers Cohort (BC-HTC) and current analysisCriteria for Inclusion in BC-HTCAll individuals:• tested at the centralized provincial laboratory for HCV or HIV OR• reported in BC as a confirmed case of HCV OR• reported in BC enhanced surveillance system as a confirmed case of HIV or AIDS (all reports) OR• reported in BC as a confirmed case of HBV OR• reported in BC as a confirmed case of active TB (latent cases excluded) OR• included in BC Enhanced Strain Surveillance System (EHSSS) as an acute HBV or HCV caseAll individuals meeting at least one the above criteria were linked internally across all their tests and case reports. Thosewith a valid personal health number (PHN) were then sent for deterministic linkage with province-wide Cancer and Ministryof Health (MoH) datasetsProvincial Communicable Disease Data Sources• BC-PHL HIV laboratory testing datasets (tests: ELISA, Western blot, NAAT, p24, culture)• BC-PHL HCV laboratory tests datasets (tests: antibody, HCV RNA, genotyping)• HIV/AIDS Information System (HAISYS) (public health HIV/AIDS case reports)• Integrated Public Health information System (iPHIS) (public health case reports of HCV, HBV, and TB)• Enhanced Strain Surveillance System (EHSSS) (risk factor data on a subset of acute HCV and acute HBV cases)Data Date Ranges:HIV lab data: 1988–2013HCV lab data: 1992–2013HAISYS: 1980–2013iPHIS: 1990–2013EHSSS: 2000–2013Cancer and MoH Administrative Data Sources• BC Cancer Registry (BCCR) (primary tumour registry, excludes metastatic cancers)• Discharge Abstracts Dataset (DAD) (hospitalization records)• Medical Services Plan (MSP) (physician diagnostic and billing data)• PharmaCare/PharmaNet (Pharma) (prescription drug dispensations)• BC Vital Statistics (VS) (deaths registry)Data Date Ranges:BCCR: 1970–2012DAD: 1985–2013Q1MSP: 1990–2012Pharma: 1985–2012VS: 1985–2013The final BC-HTC comprises all individuals successfully linked on PHN to the MoH Client Roster (a registry of all BC residentsenrolled in the publicly-funded universal healthcare system)Eligibility for current analysis• all subjects included in final, linked BC-HTC with at least one valid HCV test (antibody, HCV RNA, or genotype) (1992–2013)or HCV case report (1990–2013)• subjects were censored for analysis date of death or December 31, 2013, whichever came first• excluded all data preceding subject’s recorded date of birth• excluded all data occurring more than 7 days after subject’s recorded date of death• excluded HCV antibody tests in infants less than 18 months in the absence of HCV RNA confirmatory testingJanjua et al. BMC Infectious Diseases  (2016) 16:334 Page 2 of 14DefinitionsA HCV case was defined as an individual testing positivefor either HCV antibody or RNA or genotype or wasreported as a HCV case through the public healthreporting system [15]. We considered participants whowere HCV antibody positive at their first test on recordas having prevalent infection as, without a prior nega-tive test, a seroconversion interval cannot be estab-lished and, based on natural history, most will bechronically infected. Those cases not found in labora-tory data but reported by public health as confirmedHCV were considered prevalent infections. Individualswith a negative followed by a positive test were consid-ered seroconverters or new infections. Individuals whoseroconverted within 24 months of the last negativetest were termed 24-month seroconverters, while thosewho seroconverted after 24 months are >24-monthsseroconverters. For surveillance purposes in BC, acuteHCV infection is defined as seroconversion within theprevious 12 months [15]. Since the characteristics of12- and 24-month seroconverters were similar as pre-sented in Additional file 1: Table S2, we report 0–24-month seroconverters as acute HCV cases. Co-infectionwas defined as being infected with HIV, HBV or activeTB together with HCV.Socioeconomic status was assessed using the QuébecIndex of Material and Social Deprivation, a widely usedindex based on Canadian Census data [16]. Data fromeach census, conducted every 5 years, was applied totwo years before and two years after the census year. Forthe 2011 census, the index is based on the data productCensusPlus to address non-response related bias in the2011 National Household Survey [17].Assessment of illicit drug use, mental illnesses, andproblematic alcohol use was based on having diag-nostic codes in administrative health datasets evalu-ated across all data prior to and within 3 years ofthe first positive test or last negative test (Additionalfile 1: Table S1).Statistical analysisWe compared the characteristics of HCV positive cases(24-month seroconverters, >24-month seroconvertersand prevalent cases) and negative groups using the chi-square test for categorical factors or the Wilcoxon-Mann-Whitney test for continuous variables. We calcu-lated HCV positivity across birth cohorts and comparedtheir characteristics. Positivity rate is defined as numberof hepatitis C diagnoses divided by the total number ofpeople tested for hepatitis C. We performed multi-nomial logistic regression to assess the factors associ-ated with new and prevalent infections at diagnosiscompared to HCV negatives.ResultsParticipant Profile, testing and infection prevalenceThe cohort included 1,132,855 subjects tested for hepa-titis C from 1992-2013. Of these, 64,634 (5.7 %) wereHCV positive. An additional 3092 cases tested elsewhereand reported to the public health surveillance systemfrom 1990-2013 resulted in a total of 67,726 HCV cases.Of HCV positive individuals, 11,945 (17.6 %) have diedand 55,781 were alive at the end of 2013. Among1,068,221 HCV negative individuals, 79,840 (7.5 %) havedied and 988,381 were alive at the end of 2013. The fol-lowing results are from individuals alive as of December31, 2013 unless specified otherwise.Characteristics of HCV positive and negative individualsFor HCV positive individuals, the median age at their firsttest was 40 years and 35 years for HCV negativeindividuals. A comparatively small proportion (12.2 %) ofHCV positive individuals were born after 1975 comparedto those HCV negative (37.6 %; p < 0.001). A higher propor-tion of HCV positives compared to negatives were male(64.4 % vs. 44.1 %; p < 0.001). Infection with HIV (5.7 % vs.0.5 %; p < 0.001), HBV (3.7 % vs. 2.0 %; p < 0.001) and activeTB (0.5 % vs 0.2 %; p < 0.001) were significantly higher inHCV positives than negatives. There was a graded in-crease in percent HCV positivite with increases in mater-ial (most privileged: 3.2 % vs. most deprived: 8.0 %) andsocial deprivation (most privileged: 3.1 % vs. most de-prived: 7.7 %). There were fewer privileged (material: 13.4% vs. 22.0 %/social: 11.0 % vs 18.5 %) and more deprived(material: 29.6 % vs. 18.8 %; p < 0.001/social: 37.7 % vs.24.8 %; p < 0.001) individuals among HCV positives com-pared to HCV negatives. The proportions with illicit druguse (35.2 % vs. 7.0 %), problematic alcohol use (21.7 % vs.6.2 %) and mental health conditions (16.0 % vs. 12.0 %) atdiagnosis were also higher among HCV positives com-pared to HCV negatives (Table 2).Seroconversion and characteristics of new and prevalentHCV casesOf 370,741 individuals who tested for anti-HCV multipletimes since 1992, 7726 (2.1 %) seroconverted. Amongthe 346,428 currently alive repeat testers, 6922 (2.0 %)seroconverted. Among those testing only once (n =762,114), 56,908 (7.5 %) tested positive (prevalent HCVinfections). Of these, 695,137 were alive at the end of2013 and 46,262 (6.7 %) were positive.Of the 6922 currently alive seroconverters, 1989 (28.7 %)seroconverted within 12 months, 1497 (21.6 %) in 12-24months and 3436 (49.6 %) >24-months after their last nega-tive test (Additional file 1: Table S2).24-month seroconverters and reported acute caseswere younger than both >24-month seroconverters andindividuals with prevalent infection (median ages: 30, 35,Janjua et al. BMC Infectious Diseases  (2016) 16:334 Page 3 of 14Table 2 Characteristics of HCV positive and negative individuals, BC-HTC, Canada, 1990-2013HCV + ve group HCV -ve groupM24 Seroa >M24 Serob Prevalent HCV All Positives All NegativesN = 3628 N = 3436 N = 48717 N = 55781 N = 988381N (%) N (%) N (%) N (%) N (%)Age at baselinec< 15 17 (0.5) 1 (0.0) 420 (0.9) 438 (0.8) 20289 (2.1)15-24 962 (26.5) 410 (11.9) 2410 (5.0) 3782 (6.8) 145326 (14.7)25-34 1477 (40.7) 1234 (35.9) 9907 (20.3) 12618 (22.6) 259347 (26.2)35-44 827 (22.8) 1106 (32.2) 16534 (33.9) 18467 (33.1) 220626 (22.3)45-54 275 (7.6) 522 (15.2) 13068 (26.8) 13865 (24.9) 163134 (16.5)≥ 55 70 (1.9) 163 (4.7) 6378 (13.1) 6611 (11.9) 179659 (18.2)Median [IQR] 30 [24-37] 35 [28-43] 42 [34-49] 41 [33-48] 37 [28-50]Age at 1st test< 15 100 (2.8) 84 (2.4) 421 (0.9) 605 (1.1) 25860 (2.6)15-24 1485 (40.9) 1128 (32.8) 2422 (5.0) 5035 (9.0) 189747 (19.2)25-34 1225 (33.8) 1278 (37.2) 9927 (20.4) 12430 (22.3) 261056 (26.4)35-44 605 (16.7) 712 (20.7) 16590 (34.1) 17907 (32.1) 208398 (21.1)45-54 169 (4.7) 195 (5.7) 13063 (26.8) 13427 (24.1) 147688 (14.9)≥ 55 44 (1.2) 39 (1.1) 6294 (12.9) 6377 (11.4) 155632 (15.8)Median [IQR] 26 [20-34] 28 [22-35] 42 [34-49] 40 [32-48] 35 [26-48]Birth year< 1945 31 (0.9) 35 (1.0) 3102 (6.4) 3168 (5.7) 95848 (9.7)1945-1964 776 (21.4) 1037 (30.2) 32133 (66.0) 33946 (60.9) 310845 (31.5)1965-1974 1176 (32.4) 1214 (35.3) 9493 (19.5) 11883 (21.3) 209956 (21.2)≥ 1975 1645 (45.3) 1150 (33.5) 3989 (8.2) 6784 (12.2) 371732 (37.6)SexFemale 1728 (47.6) 1380 (40.2) 16741 (34.4) 19849 (35.6) 551952 (55.8)Male 1900 (52.4) 2056 (59.8) 31970 (65.6) 35926 (64.4) 436287 (44.1)Unknown 0 (0.0) 0 (0.0) 6 (0.0) 6 (0.0) 142 (0.0)Year of diagnosis1990-1994 85 (2.3) 4 (0.1) 3978 (8.2) 4067 (7.3) 3913 (0.4)1995-1999 726 (20.0) 353 (10.3) 17936 (36.8) 19015 (34.1) 104863 (10.6)2000-2004 1177 (32.4) 939 (27.3) 11733 (24.1) 13849 (24.8) 172888 (17.5)2005-2009 994 (27.4) 1280 (37.3) 9130 (18.7) 11404 (20.4) 272886 (27.6)2010-2013 646 (17.8) 860 (25.0) 5940 (12.2) 7446 (13.4) 433831 (43.9)HIV/AIDS at baselineUnknown 3450 (95.1) 3207 (93.3) 47568 (97.6) 54225 (97.2) 984182 (99.6)Yes 178 (4.9) 229 (6.7) 1149 (2.4) 1556 (2.8) 4199 (0.4)HIV/AIDS (ever)Unknown 3264 (90.0) 3104 (90.3) 46257 (95.0) 52625 (94.3) 983694 (99.5)Yes 364 (10.0) 332 (9.7) 2460 (5.0) 3156 (5.7) 4687 (0.5)HBV at baselineNo/Unknown 3528 (97.2) 3349 (97.5) 48197 (98.9) 55074 (98.7) 974223 (98.6)Yes 100 (2.8) 87 (2.5) 520 (1.1) 707 (1.3) 14158 (1.4)Janjua et al. BMC Infectious Diseases  (2016) 16:334 Page 4 of 14Table 2 Characteristics of HCV positive and negative individuals, BC-HTC, Canada, 1990-2013 (Continued)HBV (ever)No/Unknown 3453 (95.2) 3326 (96.8) 46927 (96.3) 53706 (96.3) 968459 (98.0)Yes 175 (4.8) 110 (3.2) 1790 (3.7) 2075 (3.7) 19922 (2.0)Active TB at baselineNo/Unknown 3621 (99.8) 3428 (99.8) 48634 (99.8) 55683 (99.8) 986909 (99.9)Yes 7 (0.2) 8 (0.2) 83 (0.2) 98 (0.2) 1472 (0.1)Active TB (ever)No/Unknown 3611 (99.5) 3415 (99.4) 48466 (99.5) 55492 (99.5) 986473 (99.8)Yes 17 (0.5) 21 (0.6) 251 (0.5) 289 (0.5) 1908 (0.2)Material deprivation quintile at baselineUnknown 96 (2.7) 79 (2.3) 2316 (4.8) 2491 (4.5) 14773 (1.5)Q1 (most privileged) 452 (12.5) 444 (12.9) 6247 (12.8) 7143 (12.8) 214007 (21.7)Q2 526 (14.5) 463 (13.5) 7500 (15.4) 8489 (15.2) 187587 (19)Q3 531 (14.6) 585 (17.0) 8522 (17.5) 9638 (17.3) 192265 (19.5)Q4 876 (24.2) 774 (22.5) 10580 (21.7) 12230 (21.9) 197116 (19.9)Q5 (most deprived) 1147 (31.6) 1091 (31.8) 13552 (27.8) 15790 (28.3) 182633 (18.5)Social deprivation quintile at baselineUnknown 96 (2.7) 79 (2.3) 2316 (4.8) 2491 (4.5) 14773 (1.5)Q1 (most privileged) 271 (7.5) 283 (8.2) 5302 (10.9) 5856 (10.5) 180214 (18.2)Q2 349 (9.6) 337 (9.8) 6194 (12.7) 6880 (12.3) 175098 (17.7)Q3 540 (14.9) 463 (13.5) 8094 (16.6) 9097 (16.3) 175715 (17.8)Q4 703 (19.4) 720 (21.0) 9972 (20.5) 11395 (20.4) 201551 (20.4)Q5 (most deprived) 1669 (46.0) 1554 (45.2) 16839 (34.6) 20062 (36) 241030 (24.4)Mental health at baselinedNo/Unknown 2199 (64.5) 2096 (65.0) 40934 (86.7) 45229 (84.0) 729398 (88.0)Yes 1209 (35.5) 1130 (35.0) 6297 (13.3) 8636 (16.0) 99054 (12.0)Mental health 3yrs pre-baselinedNo/Unknown 2590 (76.0) 2653 (82.2) 43518 (92.1) 48761 (90.5) 781042 (94.3)Yes 818 (24.0) 573 (17.8) 3713 (7.9) 5104 (9.5) 47410 (5.7)Illicit drug use at baselinedNo/Unknown 910 (26.7) 942 (29.2) 33036 (69.9) 34888 (64.8) 770499 (93.0)Yes 2498 (73.3) 2284 (70.8) 14195 (30.1) 18977 (35.2) 57953 (7.0)Illicit drug use 3yrs pre-baselinedNo/Unknown 1084 (31.8) 1433 (44.4) 36193 (76.6) 38710 (71.9) 795325 (96.0)Yes 2324 (68.2) 1793 (55.6) 11038 (23.4) 15155 (28.1) 33127 (4.0)Problematic alcohol use at baselinedNo/Unknown 2083 (61.1) 1896 (58.8) 38178 (80.8) 42157 (78.3) 777271 (93.8)Yes 1325 (38.9) 1330 (41.2) 9053 (19.2) 11708 (21.7) 51181 (6.2)Problematic alcohol use 3yrs pre-baselinedNo/Unknown 2521 (74.0) 2555 (79.2) 41709 (88.3) 46785 (86.9) 802492 (96.9)Yes 887 (26.0) 671 (20.8) 5522 (11.7) 7080 (13.1) 25960 (3.1)a24-month Sero: Individuals who seroconverted within 24 months of the last negative testbIndividuals who seroconverted after 24 months of the last negative testcBaseline is defined as date of diagnosis (i.e. first HCV positive test or case report) for HCV positive individuals, and date of last negative test result for HCVnegative individualsdMental health, drug misuse, alcohol misuse data was available up to 2012Janjua et al. BMC Infectious Diseases  (2016) 16:334 Page 5 of 1442 years; p < 0.001). Most of the individuals with preva-lent infection (66.0 %) were born between 1945-64 withanother 19.5 % between 1965-74. Of 24-month serocon-verters, 32.4 % were born in 1965-74, and 45.3 % after1975. A higher percentage of prevalent cases and >24-month seroconverters were male compared to 24-monthseroconverters (65.6 %, 59.8 % vs 52.4 %) (Table 2).HIV and HBV co-infections were higher among 24-month seroconverters compared to prevalent HCV cases(HIV: 10.0 % vs. 5.1 %; HBV: 4.8 % vs. 3.7 %) while theproportion with active TB was the same (0.5 % vs. 0.5 %)(Fig. 1a). The proportions with illicit drug use (73.3 %vs. 30.1 %), problem alcohol use (38.9 % vs. 19.2 %) andmental health conditions (35.5 % vs. 13.3 %) were alsohigher among 24-month seroconverters than individualswith prevalent HCV infection (Table 2, Fig. 1b).Characteristics of participants diagnosed in recent years(2010-2013) are presented in Additional file 1: Table S3.Overall characteristics are similar with differences in ageat diagnosis, birth cohort, HIV, HBV infection, and mentalillness mainly in 24 month seroconverters.HCV infection by birth cohortHCV positivity rates showed a strong birth cohort effect(Fig. 2a, b Additional file 1: Figure S1). Birth cohorts1950-1954 and 1955-59 had the highest percentage posi-tive overall followed by 1960-64 though positivity declinedover time and was lowest in 2013. Birth cohorts 1945-49abFig. 1 a Distribution of illicit drug use, alcohol use, and mental illness by HCV infection status in BC-HTC, Canada 1990-2013. b Distribution of co-infectionsby HCV infection status in BC-HTC, Canada 1990-2013Janjua et al. BMC Infectious Diseases  (2016) 16:334 Page 6 of 14and 1965-69 had similar percentage positive though it wasslightly higher for 1945-49. In 2013, there were 1,262,121people born between 1945 and 1964 living in BC; 344,791(27.3 %) have been tested and 33,946 (9.8 %) were HCVpositive, of whom 7352 (17.8 %) have already died. As-suming constant in and outflow, about 70 % of 1945-64and 1950-70 birth cohorts have not been tested for HCV.In birth cohort 1945-64, 67.8 % were male comparedto 63.9 % and 51.9 % of those born 1965-74 and after1975, respectively. A small proportion (2.3 %) of 24-month seroconverters was identified among HCV posi-tives born 1945-64 compared to 9.9 % and 24.3 % among1965-1974 and ≥1975 birth cohorts, respectively. In con-trast, 97.9 %, 94.7 %, 79.9 % and 58.8 % HCV positive testsabFig. 2 a Hepatitis C positivity by birth cohort in BC-HTC, British Columbia, Canada 1990-2013. HCV positives include both seroconverters and chronicHCV. b Hepatitis C positivity by birth cohort and year in BC-HTC, British Columbia, Canada, 2001-2013Janjua et al. BMC Infectious Diseases  (2016) 16:334 Page 7 of 14were detected on the first test (prevalent infections)among those born <1945, 1945-64, 1965-1974, and ≥1975,respectively (Table 3).The proportion of HCV/HIV co-infected individualsincreased with increasing birth year (<1945: 1.0 %, 1945-64: 4.7 %, 1965-1974: 9.0 % and >1975: 6.6 %). In con-trast, among HCV negative individuals, the HIV infec-tion rates by birth cohort were higher among thoseborn between 1945-64 and 1965-74. HBV co-infectionwas 2.9 %, 3.8 %, 4.7 % and 1.9 % among those born<1945, 1945-64, 1965-1974, and ≥1975, respectively. Illicitdrug use (36.7 % vs 10.4 %), problematic alcohol use (22.3% vs 11.7 %) and mental health conditions (16.4 % vs 10.2%) were higher among those born after 1945 than thoseborn before 1945 (Table 3).Factors associated with new and prevalent HCV infectionIn the multivariable multinomial logistic regressionmodel (Table 4), new HCV infections were associatedwith being male, born after 1945, HIV co-infection, HBVco-infection, material deprivation, illicit drug use, prob-lematic alcohol use and mental health diagnoses. Thesame factors were associated with prevalent HCV infec-tions except for lower odds for HBV co-infection, mentalhealth conditions and birth cohort ≥ 1975. The odds ofprevalent infection were highest in the 1945-54 birthcohort (OR: 3.8, 95 % CI: 3.7-3.9) followed by 1955-64(OR: 3.2, 95 % CI: 3.1-3.3), while the odds of being a newinfection were highest for the 1975-84 (OR: 11.8, 95 % CI:9.9-14.1) birth cohort followed by those born 1965-74(OR: 9.9, 95 % CI: 8.3-11.8). Furthermore, odds ratios forillicit drug use (ORs: 21.0, 95 % CI: 19.8-22.4 vs. 5.0, 95 %CI: 4.9-5.2) and HIV co-infection (ORs: 7.2, 95 % CI: 7.1-8.9 vs. 4.8, 95 % CI: 4.5-5.2) were much higher for new in-fections than for prevalent HCV infections. In a modelwith age at diagnosis instead of birth cohort (Additionalfile 1: Table S5), odds of prevalent infection were highestamong ages 45-54 years (OR: 4.0; 95 % CI: 3.9-4.2)followed by 35-44 years (OR: 3.2; 95 % CI: 3.0-3.3) whileodds for new infection were highest among ages 15-24years (OR: 11.4, 95 % CI: 9.0-14.4) and 25-34 years (OR:11.1, 95 % CI: 8.8-14.0) and declined thereafter. Similarresults were observed using indicators for recent risk ac-tivities (Additional file 1: Table S6).DiscussionWe used a large cohort of more than one million peopletested for HCV in BC, and while accounting for mortal-ity, we found that a large number of people are currentlyliving with HCV. The highest positivity rate was amongpeople born in 1945-64, which declined over time andwas lowest in 2013. New infections were detected mainlyamong younger age groups. The new HCV infection(seroconversion) rate was highest among males, thosewith HIV or HBV co-infection, mental health conditions,problematic alcohol or illicit drug use, and socioeco-nomically disadvantaged persons. Prevalent HCV infec-tion was associated with being male, born 1945-64, HIVco-infected, problem alcohol and illicit drug use, andsocioeconomic deprivation. These findings of twin epi-demics highlight important opportunities for prevention,testing and treatment of HCV.In this analysis, we identified two groups of HCV in-fected individuals: new infections (seroconverters) andthose with prevalent HCV infection. Most of those withprevalent HCV were born 1945-1964, while most newlyinfected individuals were younger. However, the sero-converters are not a homogeneous group: 24-month ser-oconverters differed from >24 months seroconverters interms of age, sex, testing patterns, and HBV co-infectionrate. Surveillance data on acute HCV infections indicatethat 70 % of seroconverters reported injection drug usein the past 12 months [18]. In a BC-HTC subset forwhom self-reported risk factor data was available, 85 %of those who self-reported injection drug use had a med-ical visit for illicit drug use. Thus, 24-month seroconver-ters most likely acquired HCV through their injectiondrug use networks.Most of the HCV cases, especially prevalent infections,were identified among those born 1945-64 and the posi-tivity rate was much higher in this group, especially forthose born 1950-1960. Similarly high 1945-64 birth co-hort positivity rates have been reported in various stud-ies from the United States [19–22]. Using reported HCVcases in Canada, Trubnikov et al. found the highestHCV prevalence among the 1950-54 and 1955-59 birthcohorts, followed by 1960-64 and 1966-69, while preva-lence among those born 1945-49 was lower than forthose born 1965-69 [2]. In contrast, in our study, thepositivity rate for birth cohort 1945-49 was higher thanfor birth cohort 1965-69 (Fig. 2). Our findings are alsoconsistent with a study which assessed HCV related hos-pital admissions where the 1950-54 and 1955-59 birthcohorts had the highest rates [23]. Although the posi-tivity rate is still highest among the 1945-64 birth co-hort, the rate in this cohort has been declining oversuccessive years suggesting a decreasing pool of un-diagnosed prevalent HCV infections. Canada has hadrisk based testing guidelines since 1994 [24]. The de-clining positivity rate in this birth cohort suggeststhat testing driven by risk based guidelines have beenable to identify most people with current or past riskactivities and diagnose most of the HCV infections inthis cohort. However, risk based testing may notidentify individuals who are unable to recall or areunwilling to disclose remote risk behaviors. The USPreventive Services Task Force has recommended onetime testing of individuals born 1945-65 [22]. FurtherJanjua et al. BMC Infectious Diseases  (2016) 16:334 Page 8 of 14Table 3 Characteristics of currently alive HCV testers by HCV status and birth cohort, Canada, BC-HTC, 1990-2013HCV Positive HCV Negative<1945 1945-1964 1965-1974 ≥1975 <1945 1945-1964 1965-1974 ≥1975N = 3168 N = 33946 N = 11883 N = 6784 N = 95848 N = 310845 N = 209956 N = 371732N (%) N (%) N(%) N (%) N (%) N(%) N (%) N (%)Age at baselinea< 15 0 0 0 438 (6.5) 0 0 0 20289 (5.5)15-24 0 0 857 (7.2) 2925 (43.1) 0 0 3591 (1.7) 141735 (38.1)25-34 0 2764 (8.1) 6688 (56.3) 3166 (46.7) 0 6369 (2.1) 66420 (31.6) 186558 (50.2)35-44 0 14198 (41.8) 4014 (33.8) 255 (3.8) 0 73286 (23.6) 124190 (59.2) 23150 (6.2)45-54 425 (13.4) 13116 (38.6) 324 (2.7) 0 3166 (3.3) 144213 (46.4) 15755 (7.5) 0≥ 55 2743 (86.6) 3868 (11.4) 0 0 92682 (96.7) 86977 (28.0) 0 0Median [IQR] 63 [58-70] 45 [39-50] 32 [28-37] 25 [21–29] 69 [63-75] 50 [44-55] 37 [33-41] 26 [21–30]Age at 1st test< 15 0 0 0 605 (8.9) 0 0 0 25860 (7)15-24 0 0 1205 (10.1) 3830 (56.5) 0 0 7867 (3.8) 181880 (48.9)25-34 0 3074 (9.1) 7174 (60.4) 2182 (32.2) 0 12382 (4.0) 96703 (46.1) 151971 (40.9)35-44 0 14485 (42.7) 3255 (27.4) 167 (2.5) 0 99462 (32.0) 96915 (46.2) 12021 (3.2)45-54 436 (13.8) 12742 (37.5) 249 (2.1) 0 5217 (5.4) 134000 (43.1) 8471 (4.0) 0≥ 55 2732 (86.2) 3645 (10.7) 0 0 90631 (94.6) 65001 (20.9) 0 0Median [IQR] 63 [58-69] 44 [39-50] 31 [27-36] 22 [18–27] 67 [61-73] 48 [42-53] 35 [30-39] 24 [20–28]SexFemale 1354 (42.7) 10946 (32.3) 4288 (36.1) 3261 (48.1) 51063 (53.3) 164778 (53.0) 116339 (55.4) 219772 (59.1)Male 1809 (57.1) 23000 (67.8) 7594 (63.9) 3523 (51.9) 44657 (46.6) 146061 (47.0) 93615 (44.6) 151954 (40.9)Unknown 5 (0.2) 0 0 0 128 (0.1) 6 (0.0) 2 (0.0) 6 (0.0)Year of diagnosis1990-1994 340 (10.7) 2938 (8.7) 690 (5.8) 99 (1.5) 822 (0.9) 1858 (0.6) 889 (0.4) 344 (0.1)1995-1999 1186 (37.4) 12980 (38.2) 3992 (33.6) 857 (12.6) 21815 (22.8) 48746 (15.7) 21003 (10.0) 13299 (3.6)2000-2004 703 (22.2) 8333 (24.6) 3163 (26.6) 1650 (24.3) 19159 (20.0) 68035 (21.9) 43673 (20.8) 42021 (11.3)2005-2009 555 (17.5) 6004 (17.7) 2588 (21.8) 2257 (33.3) 22709 (23.7) 81513 (26.2) 63756 (30.4) 104908 (28.2)2010-2013 384 (12.1) 3691 (10.9) 1450 (12.2) 1921 (28.3) 31343 (32.7) 110693 (35.6) 80635 (38.4) 211160 (56.8)HIV/AIDS at baselineNo/Unknown 3149 (99.4) 33150 (97.7) 11364 (95.6) 6562 (96.7) 95664 (99.8) 308950 (99.4) 208736 (99.4) 370832 (99.8)Yes 19 (0.6) 796 (2.3) 519 (4.4) 222 (3.3) 184 (0.2) 1895 (0.6) 1220 (0.6) 900 (0.2)Janjuaetal.BMCInfectiousDiseases (2016) 16:334 Page9of14Table 3 Characteristics of currently alive HCV testers by HCV status and birth cohort, Canada, BC-HTC, 1990-2013 (Continued)HIV/AIDS co-infection (ever)No/Unknown 3135 (99.0) 32345 (95.3) 10810 (91.0) 6335 (93.4) 95640 (99.8) 308728 (99.3) 208587 (99.4) 370739 (99.7)Yes 33 (1.0) 1601 (4.7) 1073 (9.0) 449 (6.6) 208 (0.2) 2117 (0.7) 1369 (0.7) 993 (0.3)HBV at baselineNo/Unknown 3130 (98.8) 33529 (98.8) 11686 (98.3) 6729 (99.2) 94660 (98.8) 304567 (98.0) 206304 (98.3) 368692 (99.2)Yes 38 (1.2) 417 (1.2) 197 (1.7) 55 (0.8) 1188 (1.2) 6278 (2.0) 3652 (1.7) 3040 (0.8)HBV co-infection (ever)No/Unknown 3075 (97.1) 32643 (96.2) 11330 (95.4) 6658 (98.1) 94059 (98.1) 302130 (97.2) 204856 (97.6) 367414 (98.8)Yes 93 (2.9) 1303 (3.8) 553 (4.7) 126 (1.9) 1789 (1.9) 8715 (2.8) 5100 (2.4) 4318 (1.2)Active TB at baselineNo/Unknown 3157 (99.7) 33890 (99.8) 11863 (99.8) 6773 (99.8) 95584 (99.7) 310307 (99.8) 209650 (99.9) 371368 (99.9)Yes 11 (0.4) 56 (0.2) 20 (0.2) 11 (0.2) 264 (0.3) 538 (0.2) 306 (0.2) 364 (0.1)Active TB co-infection (ever)No/Unknown 3149 (99.4) 33783 (99.5) 11808 (99.4) 6752 (99.5) 95494 (99.6) 310145 (99.8) 209558 (99.8) 371276 (99.9)Yes 19 (0.6) 163 (0.5) 75 (0.6) 32 (0.5) 354 (0.4) 700 (0.2) 398 (0.2) 456 (0.1)Material deprivation quintile at baselineUnknown 106 (3.4) 1298 (3.8) 618 (5.2) 469 (6.9) 1199 (1.3) 3720 (1.2) 2671 (1.3) 7183 (1.9)Q1 (most privileged) 507 (16.0) 4444 (13.1) 1362 (11.5) 830 (12.2) 18845 (19.7) 65327 (21.0) 48322 (23.0) 81513 (21.9)Q2 513 (16.2) 5404 (15.9) 1636 (13.8) 936 (13.8) 18165 (19.0) 60803 (19.6) 39355 (18.7) 69264 (18.6)Q3 533 (16.8) 6114 (18) 1926 (16.2) 1065 (15.7) 19060 (19.9) 61814 (19.9) 40022 (19.1) 71369 (19.2)Q4 660 (20.8) 7365 (21.7) 2691 (22.7) 1514 (22.3) 20032 (20.9) 61824 (19.9) 40792 (19.4) 74468 (20.0)Q5 (most deprived) 849 (26.8) 9321 (27.5) 3650 (30.7) 1970 (29.0) 18547 (19.4) 57357 (18.5) 38794 (18.5) 67935 (18.3)Social deprivation quintile at baselineUnknown 106 (3.4) 1298 (3.8) 618 (5.2) 469 (6.9) 1199 (1.3) 3720 (1.2) 2671 (1.3) 7183 (1.9)Q1 (most privileged) 557 (17.6) 3477 (10.2) 1081 (9.1) 741 (10.9) 17348 (18.1) 57695 (18.6) 36550 (17.4) 68621 (18.5)Q2 513 (16.2) 4335 (12.8) 1238 (10.4) 794 (11.7) 17802 (18.6) 56839 (18.3) 36109 (17.2) 64348 (17.3)Q3 516 (16.3) 5802 (17.1) 1790 (15.1) 989 (14.6) 17342 (18.1) 56864 (18.3) 36204 (17.2) 65305 (17.6)Q4 606 (19.1) 7152 (21.1) 2380 (20.0) 1257 (18.5) 19201 (20.0) 62437 (20.1) 42960 (20.5) 76953 (20.7)Q5 (most deprived) 870 (27.5) 11882 (35.0) 4776 (40.2) 2534 (37.4) 22956 (24.0) 73290 (23.6) 55462 (26.4) 89322 (24.0)Mental illness at baselinebNo/Unknown 2768 (89.8) 28051 (85.0) 9468 (81.9) 4942 (79.5) 75892 (90.3) 230429 (85.6) 160387 (87.7) 262690 (89.8)Yes 316 (10.2) 4956 (15.0) 2087 (18.1) 1277 (20.5) 8130 (9.7) 38636 (14.4) 22397 (12.3) 29891 (10.2)Janjuaetal.BMCInfectiousDiseases (2016) 16:334 Page10of14Table 3 Characteristics of currently alive HCV testers by HCV status and birth cohort, Canada, BC-HTC, 1990-2013 (Continued)Mental illness 3yr pre- baselinebNo/Unknown 2908 (94.3) 30114 (91.2) 10261 (88.8) 5478 (88.1) 80387 (95.7) 251001 (93.3) 172141 (94.2) 277513 (94.8)Yes 176 (5.7) 2893 (8.8) 1294 (11.2) 741 (11.9) 3635 (4.3) 18064 (6.7) 10643 (5.8) 15068 (5.2)Illicit drug use at baselinebNo/Unknown 2763 (89.6) 22649 (68.6) 6220 (53.8) 3256 (52.4) 81535 (97.0) 249677 (92.8) 167729 (91.8) 271558 (92.8)Yes 321 (10.4) 10358 (31.4) 5335 (46.2) 2963 (47.6) 2487 (3.0) 19388 (7.2) 15055 (8.2) 21023 (7.2)Illicit drug use 3yr pre- baselinebNo/Unknown 2870 (93.1) 25193 (76.3) 7090 (61.4) 3557 (57.2) 83133 (98.9) 259681 (96.5) 174045 (95.2) 278466 (95.2)Yes 214 (6.9) 7814 (23.7) 4465 (38.6) 2662 (42.8) 889 (1.1) 9384 (3.5) 8739 (4.8) 14115 (4.8)Problematic alcohol use at baselinebNo/Unknown 2724 (88.3) 25720 (77.9) 8780 (76.0) 4933 (79.3) 79838 (95.0) 248826 (92.5) 171200 (93.7) 277407 (94.8)Yes 360 (11.7) 7287 (22.1) 2775 (24.0) 1286 (20.7) 4184 (5.0) 20239 (7.5) 11584 (6.3) 15174 (5.2)Problematic alcohol use 3yr pre-baselinebNo/Unknown 2870 (93.1) 28620 (86.7) 9874 (85.5) 5421 (87.2) 81897 (97.5) 258911 (96.2) 177020 (96.8) 284664 (97.3)Yes 214 (6.9) 4387 (13.3) 1681 (14.5) 798 (12.8) 2125 (2.5) 10154 (3.8) 5764 (3.2) 7917 (2.7)aBaseline is defined as date of diagnosis (i.e. first HCV positive test or case report) for HCV positive individuals, and date of last negative test result for HCV negative individualsbMental health, drug misuse, alcohol misuse data was available up to 2012Janjuaetal.BMCInfectiousDiseases (2016) 16:334 Page11of14studies on feasibility and cost effectiveness of variousstrategies are needed to identify undiagnosed infec-tions in BC.Risk factors for both new and prevalent HCV infec-tions were similar with some notable exceptions, includ-ing age, birth cohort, drug use, HBV co-infection andmental health diagnoses. HBV co-infection and mentalhealth problems were significantly associated with in-creased odds of new infection but decreased odds ofprevalent HCV infection, while ORs for illicit drug usecompared to no drug use among new infections (AOR =21) were four times than those for prevalent HCV infec-tion (AOR = 5.0). ORs for prevalent HCV infection werehighest for birth cohort 1945-64 and declined thereafter,while among new infections, ORs were highest for thoseborn later, consistent with an earlier analysis demon-strating a higher HCV incidence rate in younger birthcohorts [25]. Demographic characteristics and risk fac-tors for prevalent HCV were also consistent with recentdata from the United States and Canada [8, 20]. Like-wise, in a recent electronic medical record based studyfrom the US, being a baby boomer, male, people whoinjects drugs (PWID), HIV co-infected and having lowincome were associated with HCV positivity [26]. Riskfactors among new infections were also similar to thoseidentified with HCV infection in high risk populations,mainly PWID. Among seroconverters especially 24-months seroconverters, those born 1965-84, HIV/HBVco-infection, socioeconomic deprivation, mental illness,illicit drug use and problematic alcohol use were morecommon than among prevalent HCV infections (Table 1/Fig. 1). These findings highlight the presence of syndemicsof blood-borne infections (BBI), mental illness, addiction,and socioeconomic marginalization in this population ashas been reported by others [27–29]. Addressing thesesyndemics requires comprehensive services including inte-grated testing, prevention and treatment for STI/BBIs, aswell as mental health and addiction services to address theneeds of this population group.Findings from this paper should be interpreted inthe context of some methodological issues. The valid-ity of our estimates depends on the successful linkagerate. Linkage rates were very high for HCV (>85 %),especially in recent years [14]. Linkage rates for thoseHIV co-infected were much higher than the overallHIV linkage rate, especially before 2005. Thus, theHIV co-infection rate may have been underestimated.However, as reported earlier, we used multiple sourcesof HIV status identification to reduce underestima-tion. In this study, we did not have access to immi-gration and Aboriginal status data and hence we werenot able to characterize the disease burden amongimmigrants and Aboriginal populations. Other datasuggest that Aboriginal people are five times morelikely to be infected with HCV [30]. Immigrants fromendemic countries are also more likely to have higherHCV infection rates.Table 4 Multivariable multinomial logistic regression models forfactors associated with seroconversion and prevalent HCVinfection in BC-HTC, Canada 1990-2012a, bVariables Seroconverters Prevalent HCVORs (95 % CI) ORs (95 % CI)SexFemale 1.00 1.00Male 1.25 (1.19-1.31) 2.06 (2.02-2.10)Birth year< 1945 1.00 1.001945-1954 3.38 (2.78-4.11) 3.79 (3.67-3.92)1955-1964 6.22 (5.19-7.44) 3.23 (3.13-3.34)1965-1974 9.86 (8.26-11.78) 1.64 (1.58-1.70)1975-1984 11.76 (9.83-14.07) 0.70 (0.67-0.73)≥ 1985 6.53 (5.34-7.99) 0.48 (0.44-0.51)HIV infection at baselinecNo/Unknown 1.00 1.00Yes 7.92 (7.05-8.89) 4.80 (4.47-5.15)HBV at baselinecNo/Unknown 1.00 1.00Yes 2.33 (2.00-2.71) 0.69 (0.63-0.75)Active TB at baselinecNo/Unknown 1.00 1.00Yes 1.00 (0.62-1.62) 1.01 (0.81-1.25)Material deprivation quintile atbaselinecUnknown 3.51 (2.96-4.17) 5.38 (5.07-5.70)Q1 (most privileged) 1.00 1.00Q2 1.20 (1.06-1.31) 1.22 (1.18-1.27)Q3 1.24 (1.13-1.36) 1.36 (1.32-1.41)Q4 1.62 (1.48-1.76) 1.60 (1.55-1.65)Q5 (most deprived) 1.99 (1.83-2.15) 1.98 (1.92-2.04)Mental illness at baselinecNo/Unknown 1.00 1.00Yes 1.18 (1.12-1.25) 0.69 (0.67-0.72)Illicit drugs use at baselineNo/Unknown 1.00 1.00Yes 21.00 (19.80-22.38) 5.03 (4.91-5.16)Problematic alcohol use atbaselineNo/Unknown 1.00 1.00Yes 2.11 (2.00-2.23) 1.67 (1.63-1.72)aAdjusted for health authority and year of diagnosis; bExcluding unknowngender and health authority. cBaseline is defined as time of diagnosis for HCVpositive, and date of last negative for HCV negativeJanjua et al. BMC Infectious Diseases  (2016) 16:334 Page 12 of 14To date, laboratory testing for HCV has followed riskbased guidelines and hence a higher positivity rateamong HCV testers in this cohort is expected comparedto the general population. However, general populationsurveys such as the Canadian Health Measures Surveymay not capture high risk populations with higher HCVprevalence thus and may underestimate total populationof infected individuals [8, 20]. Categorizing prevalentinfections based on being positive at the first test may bean over-estimate as some of these individuals are likelyto be recent seroconverters as shown in our recent mo-lecular analysis [31]. The prevalent HCV case detectioncould be affected by presence of late stage symptomaticdisease or survival. Survival may also affect the differ-ence in risk factor profile between prevalent and newcases. In the BC-HTC, data is available on all cohortmembers many years before cohort initiation to assessrisk factors as presented in Table 1. Thus, for all cohortmembers regardless of first test or diagnosis date, dataon risk factors started at the same time, providing ampletime to assess risk factors from the available data. Fur-thermore, after accounting for mortality in the cohort,there was no difference in identified risk factor patternsin models including both currently alive and dead andonly those currently who are currently alive. Thus, sur-vival bias is unlikely to explain difference in risk factorprofile between prevalent and new infections. However,survival bias is not expected to be completely eliminatedespecially in early nineties, when people could have diedbefore HCV diagnosis or getting diagnosed because ofsymptoms related to late stage disease. In another ana-lysis, we found that late HCV diagnosis in relation toadvance stage liver disease (hepatocellular carcinomaand decompensated cirrhosis) was common in earlynineties and have declined substantially over time [32].In the current paper, data on RNA testing and activeinfection was not presented, which is important to assesspeople living with active infection and need treatment toprevent progressive liver disease. The BC-HTC providesa platform to assess program progress through cascadeof care monitoring, long term outcomes related to HCVand impact of treatment on long term outcomes. Thesedata are in the process of being analyzed and will be pre-sented in future reports.ConclusionsThe HCV positivity rate was highest in the 1950-54 and1955-59 birth cohorts and overall among those bornbetween 1945- 1964, which declined over time. Further-more, the year over year decline in the positivity ratesuggests that most of the HCV infections in these co-horts have already been identified. However, current riskbased testing may not identify individuals who are un-able to recall or are unwilling to disclose remote riskbehaviors. Further studies are needed to estimate thenumber of undiagnosed HCV infection and assess opti-mal strategies to identify the remaining undiagnosed in-fections. Newly acquired infections are occurring mainlyin younger birth cohorts and these groups are morelikely to be co-infected with HIV and/or HBV, socioeco-nomically marginalized, and living with serious mentalillnesses and addictions. Comprehensive syndemic ap-proaches that take into account co-infections, mentalhealth, additions and socioeconomic vulnerabilities areurgently required to identify, treat, and support peoplewith HCV infection.Additional fileAdditional file 1: Table S1. Definitions for comorbid conditions. TableS2. Distribution HCV seroconverters by seroconversion interval in BC HTC,Canada 1990-2013. Table S3. Characteristics of currently alive recently diag-nosed (2010-2013) HCV positive and negative individuals, BC-HTC, 2010 - 2013.Table S4. Percentage positive for hepatitis C by diagnosis year and birthcohort in British Columbia, 1992-2013. Figure S1. Hepatitis C percentagepositive by year of diagnosis and birth cohort, BC-HTC, British Columbia,Canada, 2000-2013. Table S5. Multivariable multinomial logistic regressionmodel for factors associated with seroconversion and chronic HCV infectionincluding age as covariate in BC HTC, Canada 1990-2012 a,b. Table S6. Multi-variable multinomial logistic regression model for factors associated withseroconversion and chronic HCV infection including indicators for recent riskactivities in BC HTC, Canada 1990-2012 a,b. (DOCX 68 kb)AbbreviationsBC-HTC, The BC Hepatitis Testers Cohort; HCV, hepatitis C virus; BC, BritishColumbia; HIV, Human immunodeficiency virus; HBV, hepatitis B virus; TB,Tuberculosis; STIs, Sexually transmitted infections; BCCDC, British ColumbiaCenter for Disease Control; BBI, Bloodborne infection; PWID, People whoinjection drugsAcknowledgementsWe acknowledge the assistance of BCCDC, PHSA Performance measurementand reporting, Information Analysts, Ministry of Health Data Access, Researchand Stewardship, & MSP, DAD and Medical Beneficiary and PharmaceuticalServices programme areas, BC Ministry of Health, and BC Cancer Agency andtheir staff involved in data access and procurement, and data management.FundingThis work was supported by BC Centre for Disease Control and Agenciescontributing data to the study and the Canadian Institutes of Health Research[Grant # 201503NHC-348216-NHC-ADWY -62134 & 201410PHE-337680-PHE-CAAA-179547].Availability of data and materialsThe study is based on data linkage that is available through respective datastewards. Information on data access is available at BC Centre for DiseaseControl at following link: http://www.bccdc.ca/about/accountability/data-access-requests/public-health-data.Authors’ contributionsNZJ conceived of the study, participated in its design, guided the statisticalanalysis, wrote first draft, and revised the manuscript. AY participated in thedesign of the study and performed the statistical analysis. MKu and MAparticipated in the design of the study and helped to draft the manuscript.DC, JW and MT helped to draft the manuscript. MKr participated in thedesign of the study, interpretation of findings and helped to draft themanuscript. All authors read and approved the final manuscript.Janjua et al. BMC Infectious Diseases  (2016) 16:334 Page 13 of 14Competing interestsMK has received grant funding via his institution from Roche MolecularSystems, Boehringer Ingelheim, Merck, Siemens Healthcare Diagnostics andHologic Inc.Consent for publicationNot ApplicableEthics and consent to participateData linkage to establish the BC-HTC was performed under the BCCDC’s publichealth mandate. The Behavioral Research Ethics Board at the University of BritishColumbia reviewed and approved the study (H14-01649). Patient consent was notrequired as study used de-identified linked administrative healthcare datasets.Author details1Clinical Prevention Services, British Columbia Centre for Disease Control,Vancouver, BC, Canada. 2School of Population and Public Health, Universityof British Columbia, Vancouver, BC, Canada. 3Department of Pathology andLaboratory Medicine, University of British Columbia, Vancouver, BC, Canada.Received: 12 January 2016 Accepted: 13 June 2016References1. 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