The epidemiology of The epidemiology of hepatitis C infection hepatitis C infection in Ontario, 2007in Ontario, 2007Robert S. Remis MD, MPH, FRCPCRobert S. Remis MD, MPH, FRCPCDepartment of Public Health SciencesDepartment of Public Health SciencesUniversity of Toronto Ontario University of Toronto Ontario

HCV Task Force HCV Task Force Ontario Advisory Committee on HIV/AIDSOntario Advisory Committee on HIV/AIDSToronto, Ontario, May 26, 2008Toronto, Ontario, May 26, 2008

Overview of presentationOverview of presentation

Background and mandateBackground and mandate

Study objectivesStudy objectives

Methods and data sourcesMethods and data sources

Estimates of prevalence, incidence and Estimates of prevalence, incidence and sequelaesequelae

Study limitationsStudy limitations

Interpretation and recommendationsInterpretation and recommendations

BackgroundBackground

Hepatitis C prevalence estimated in Canada in Hepatitis C prevalence estimated in Canada in 1998 but limited to transfusion1998 but limited to transfusion--related infectionrelated infection

Modeling study under contract with Hepatitis C Modeling study under contract with Hepatitis C Program, Health Canada in 2003 using new Program, Health Canada in 2003 using new methodology to model HCV incidence, prevalence methodology to model HCV incidence, prevalence and and sequelaesequelae to 2002to 2002

In 2006 and 2008, methods were refined and In 2006 and 2008, methods were refined and adapted to evaluate HCV epidemiology in Ontario adapted to evaluate HCV epidemiology in Ontario under a mandate from Ontario Hepatitis C under a mandate from Ontario Hepatitis C SecretariatSecretariat

Study objectivesStudy objectives

HCV incidence and prevalence by exposure HCV incidence and prevalence by exposure category, sex and agecategory, sex and age

Proportion of infections diagnosedProportion of infections diagnosed

HCVHCV--infection by stage of diseaseinfection by stage of disease

MorbidityMorbidity

Trends in serious Trends in serious sequelaesequelae

Methods Methods 1 Estimate populations at risk1 Estimate populations at risk

Simulated population 1960Simulated population 1960--2027 from births, 2027 from births, immigration and mortalityimmigration and mortality

Stratified by country of birth: Canada Stratified by country of birth: Canada vsvs elsewhereelsewhere

Categorized into four subpopulations:Categorized into four subpopulations:

injection drug usersinjection drug users

transfusion recipientstransfusion recipients

hemophiliahemophilia

othersothers

Methods Methods 2 Model incidence & prevalence2 Model incidence & prevalence

HCV incidence in each exposure category to derive HCV incidence in each exposure category to derive prevalenceprevalence

For immigrants, prevalence at time of arrivalFor immigrants, prevalence at time of arrival

Modeled transitions related to acquisition, antibody Modeled transitions related to acquisition, antibody loss, progression through loss, progression through sequelaesequelae and mortalityand mortality

Parameter values adjusted to fit observed dataParameter values adjusted to fit observed data

Unique approach for each exposure category Unique approach for each exposure category (for transfusion,1998 study)(for transfusion,1998 study)

MethodsMethods3 Progression to serious 3 Progression to serious sequelaesequelae

Markov model through stages of HCV infectionMarkov model through stages of HCV infection

Stages: HCV infection, cirrhosis, liver failure, Stages: HCV infection, cirrhosis, liver failure, liver transplant, liver transplant, hepatocellularhepatocellular carcinomacarcinoma

Transitions stratified on sex, age and HIV statusTransitions stratified on sex, age and HIV status

Parameter values from previous studies Parameter values from previous studies

MethodsMethodsIntegrated analytic HCV modelIntegrated analytic HCV model

Integrated Markov model from through birth or Integrated Markov model from through birth or immigration, exposure, infection, progression immigration, exposure, infection, progression and mortality and mortality

Values written into spreadsheet (Excel)Values written into spreadsheet (Excel)

Model engine programmed in APL+Model engine programmed in APL+

HIV infection incorporated into model for IDUs HIV infection incorporated into model for IDUs and hemophilia patientsand hemophilia patients

Hemophilia patients modeled entirely within Hemophilia patients modeled entirely within CanadianCanadian--born populationborn population

Methods Methods Other analysesOther analyses

To determine infections diagnosed, interpolated To determine infections diagnosed, interpolated reported HCV diagnoses for missing periodsreported HCV diagnoses for missing periodsIncidence estimated using two methods: Incidence estimated using two methods:

HCV incidence among susceptible IDUs and HCV incidence among susceptible IDUs and extrapolatedextrapolatedProjected from acute HCV infections, adjusted Projected from acute HCV infections, adjusted for asymptomatic and unreported infectionsfor asymptomatic and unreported infections

Methods Methods Sources of dataSources of data

HCV prevalence in source countries, WHOHCV prevalence in source countries, WHO

Populations 1960Populations 1960--2006, Statistics Canada 2006, Statistics Canada

Seroepidemiologic data from published and Seroepidemiologic data from published and presented studies in Canada presented studies in Canada

Proportions with respect to exposure category and Proportions with respect to exposure category and place of birth, EHSSSplace of birth, EHSSS

Transition parameters, previous studies / Transition parameters, previous studies / KrahnKrahn

Reported HCV diagnoses, Health CanadaReported HCV diagnoses, Health Canada

HCV prevalence in Ontario among HCV prevalence in Ontario among persons born in Canada, 2007persons born in Canada, 2007

PopulationPopulationHCV HCV

prevalence rateprevalence rateHCV prevalence HCV prevalence

numbernumber ProportionProportion31,79131,791

ExEx--IDUIDU 64,87964,879 49%49% 31,46631,466 40%40%IDU, totalIDU, total 96,67096,670 49,85249,852 63%63%

TotalTotal 9,209,9969,209,996 0.86%0.86% 79,05179,051 100%100%

TransfusionTransfusion 863,850863,850 1.1%1.1% 9,1919,191 12%12%HemophiliaHemophilia 878878 42%42% 372372 0.5%0.5%OtherOther 8,248,5988,248,598 0.24%0.24% 19,63519,635 25%25%

18,38618,386 23%23%IDUIDU 58%58%

HCV prevalence in Ontario among HCV prevalence in Ontario among persons born elsewhere, 2007persons born elsewhere, 2007

PopulationPopulationHCV HCV

prevalence rateprevalence rateHCV prevalence HCV prevalence

numbernumber ProportionProportion5,5325,532

ExEx--IDUIDU 11,92711,927 49%49% 5,7865,786 19%19%IDU, totalIDU, total 17,45917,459 9,0339,033 29%29%

TransfusionTransfusion 391,139391,139 0.72%0.72% 2,8332,833 9%9%

TotalTotal 3,675,7553,675,755 0.83%0.83% 30,66730,667 100%100%

HemophiliaHemophiliaOtherOther 3,267,1563,267,156 0.57%0.57% 18,80118,801 61%61%

3,2473,247 11%11%IDUIDU 59%59%

HCV prevalence in Ontario by HCV prevalence in Ontario by exposure category, 2007exposure category, 2007

100%100%109,717109,7170.85%0.85%12,885,75012,885,750TotalTotal

35%35%38,43638,4360.33%0.33%11,515,75411,515,754OtherOther0.33%0.33%37237242%42%878878HemophiliaHemophilia11%11%12,02512,0251.0%1.0%1,254,9891,254,989TransfusionTransfusion

54%54%58,88558,885114,129114,129IDU, totalIDU, total34%34%37,25337,25349%49%76,80676,806ExEx--IDUIDU

37,32337,323PopulationPopulation

20%20%ProportionProportion

21,63221,632

HCV prevalence HCV prevalence numbernumber

58%58%IDUIDU

HCV HCV prevalence rateprevalence rate

Modeled number of HCVModeled number of HCV--infected infected persons by exposure category, persons by exposure category, Ontario, 2007 (n=109,717) Ontario, 2007 (n=109,717)

Hemophilia0.3%

Other35%

IDU20%

Ex-IDU34%

Transfusion11%

HCV incidence by place of birth and HCV incidence by place of birth and exposure category, Ontario, 2007exposure category, Ontario, 2007

Born in CanadaBorn in CanadaHCV incidence HCV incidence

raterate

HCV HCV incidence incidence numbernumber ProportionProportion

IDUIDU 18%18%OtherOther 0.007%0.007% 595595 20%20%TotalTotal 2,9502,950 100%100%Born elsewhereBorn elsewhere

Canada totalCanada total

TotalTotal 3,4703,470 100%100%

IDUIDU 18%18% 2,7912,791 80%80%OtherOther 0.006%0.006% 674674 19%19%

IDUIDU 19%19% 440440 85%85%OtherOther 0.002%0.002% 7979

2,3512,351

15%15%

80%80%

Modeled HIV prevalence among Modeled HIV prevalence among HCVHCV--infected persons, Ontario, 2007infected persons, Ontario, 2007

100%100%2,4142,4142382382,1762,176TotalTotal

0%0%000000OtherOther4%4%9696009696HemophiliaHemophilia0%0%000000TransfusionTransfusion

96%96%2,3182,3182382382,0802,080IDU, totalIDU, total39%39%9379379494843843ExEx--IDUIDU

1,2371,237

Born in Born in CanadaCanada

57%57%ProportionProportion

1,3811,381Total OntarioTotal Ontario

144144IDUIDU

Born Born elsewhereelsewhere

Estimated HIVEstimated HIV--HCV coHCV co--infected infected persons in Ontario, 2006persons in Ontario, 2006

HIV included in HCV model only for exposure HIV included in HCV model only for exposure categories with high HIV prevalence to account for categories with high HIV prevalence to account for competing mortalitycompeting mortality

Comprehensive analysis as of 2006 includes all Comprehensive analysis as of 2006 includes all exposure categories: MSM 658, MSMexposure categories: MSM 658, MSM--IDU 584, IDU 584, IDU 1,606, HIVIDU 1,606, HIV--endemic 63, other hetero 97, endemic 63, other hetero 97, hemophiliahemophilia 114, transfusion 3114, transfusion 3

HIVHIV--HCV coHCV co--infected persons: 3,124infected persons: 3,124

2.8% of HCV2.8% of HCV--infected persons also have HIV infected persons also have HIV

11.9% of HIV11.9% of HIV--infected persons also have HCVinfected persons also have HCV

Modeled incidence of HCV Modeled incidence of HCV sequelae, Ontario, 1967sequelae, Ontario, 1967--20272027

0

50

100

150

200

250

300

350

400

1967 1972 1977 1982 1987 1992 1997 2002 2007 2012 2017 2022 2027

CirrhosisDecompHCCTransplantHCV Deaths

Modeled prevalence of HCV Modeled prevalence of HCV sequelae, Ontario, 1967sequelae, Ontario, 1967--20272027

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

1967 1972 1977 1982 1987 1992 1997 2002 2007 2012 2017 2022 2027

CirrhosisDecompHCCTransplant

Annual reported cases of Annual reported cases of HCV infection, Ontario, 1992HCV infection, Ontario, 1992--20072007

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

1992 1994 1996 1998 2000 2002 2004 2006

Cumulative reported cases of HCV Cumulative reported cases of HCV infection, Ontario, 1992infection, Ontario, 1992--20072007

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

90,000

1992 1994 1996 1998 2000 2002 2004 2006

Modeled HCV infection among Modeled HCV infection among incarcerated persons, Ontario, 2007incarcerated persons, Ontario, 2007

Prison population: provincial 8,115, federal 3,426, Prison population: provincial 8,115, federal 3,426, total 11,541 total 11,541

Proportion with history IDU ~30%Proportion with history IDU ~30%

Provincial: HCV prevalence IDU 56%, other 0.10%Provincial: HCV prevalence IDU 56%, other 0.10%

Federal: HCV prevalence IDU 70%, other 1.0%Federal: HCV prevalence IDU 70%, other 1.0%

HCV infections: provincial 1,363, federal 743, total HCV infections: provincial 1,363, federal 743, total 2,1122,112

Crude HCV prevalence 17Crude HCV prevalence 17--22%; 9722%; 97--99% IDU 99% IDU

Modeled HCV infection in the Modeled HCV infection in the Aboriginal population, Ontario, 2007Aboriginal population, Ontario, 2007

Estimated population: 242,500 Estimated population: 242,500

Proportion IDU 4.1% (male 6.0%, female 2.4%)Proportion IDU 4.1% (male 6.0%, female 2.4%)

Number IDU 10,054 (male 7,056, female 2,998)Number IDU 10,054 (male 7,056, female 2,998)

HCV prevalence: IDUs 60%, other 0.50%HCV prevalence: IDUs 60%, other 0.50%

HCV infections: IDU 6,032, other 1,162, total HCV infections: IDU 6,032, other 1,162, total 7,194; thus, 84% of HCV infections from IDU7,194; thus, 84% of HCV infections from IDU

HCV prevalence: 3.0% (male 4.1%, female 1.9%) HCV prevalence: 3.0% (male 4.1%, female 1.9%)

Summary of findingsSummary of findings

About 110,000 persons in Ontario infected with HCV About 110,000 persons in Ontario infected with HCV as of 2007as of 2007

3,300 persons newly infected with HCV each year, 3,300 persons newly infected with HCV each year, mostly through injection drug usemostly through injection drug use

Many (~25%) HCVMany (~25%) HCV--infected persons not diagnosedinfected persons not diagnosed

Impact on health of persons in Ontario considerableImpact on health of persons in Ontario considerable

Prevalence of serious HCV Prevalence of serious HCV sequelaesequelae will continue to will continue to rise until 2027rise until 2027

Study limitationsStudy limitations

Current HCV estimates are hypotheses, not Current HCV estimates are hypotheses, not conclusions; the epidemiology of HCV infection in conclusions; the epidemiology of HCV infection in Ontario remains poorly definedOntario remains poorly defined

Impact of more efficacious therapies not modeledImpact of more efficacious therapies not modeled

EHSSS data likely biased: low participation rates EHSSS data likely biased: low participation rates and lack of data from Torontoand lack of data from Toronto

Other routes likely overOther routes likely over--estimatedestimated

Transition probabilities subject to uncertaintyTransition probabilities subject to uncertainty

AcknowledgementsAcknowledgements

Hepatitis C Secretariat, Community Health Division, Hepatitis C Secretariat, Community Health Division, Ontario Ministry of Health and LongOntario Ministry of Health and Long--Term CareTerm Care

Tom Smith, Janis TrippTom Smith, Janis Tripp

Analytic supportAnalytic supportNeil Neil HershfieldHershfieldRobert PalmerRobert Palmer

Public Health Division, Ontario Ministry of Health Public Health Division, Ontario Ministry of Health and Longand Long--Term CareTerm Care

Marie Muir, Kristie Marie Muir, Kristie WillsonWillson

Public Health Agency of CanadaPublic Health Agency of CanadaJun Wu, Anil Jun Wu, Anil DedaniDedani, Hong, Hong--Xing WuXing Wu