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Title: Estimating the prevalence of hepatitis B and C in Denmark

Proposed by:

Stine Nielsen (cand.scient.san.pub) and Peer Brehm Christensen (Professor

Department of Infectious disease, Odense University hospital, Denmark)

Proposed co-authors (alphabetical order):

Susan Cowan (SSI), Gordon Hay (University of

Glasgow), Peder Jepsen (DANVIR), Henrik Krarup (DANVIR), Jeff Lazarus (CHIP), Kåre Mølbak

(SSI), Nina Weis (DANHEP) on behalf of the DANHEP and DANVIR groups

Date: 08

December 2016

Study Rationale

The purpose of this study is to update the national estimates of the number of people living with

chronic hepatitis C (HCV) and B (HBV) in Denmark. The most recent national HBV and HCV

estimates in Denmark were based on data from 2007 [1][2]. For hepatitis C between 17.000 and

21.000 people in Denmark were estimated to have chronic infection and the vast majority (>80%)

of those infected are either current (41%) or former (43%) injecting drug users [1]. The analysis of

the 2007 data also found that less than half of the patients with chronic hepatitis C had been

diagnosed and among these patients, one in three had attended specialised care [1].

The availability of simple, tolerable direct-acting antiviral (DAA) therapies with cure rates of >90%

is one of the greatest clinical advances in the last decade. Currently, the list price of DAA therapies

is very high and to ensure sound public health planning, it is of key importance that Denmark has

up-to-date and valid estimates of the total number of people living with chronic hepatitis.

The new DAA therapies have made elimination of hepatitis C possible. This was listed as one of the

goals of the 2030 Agenda for Sustainable Development (the Sustainable Development Goals,

SGDs), adopted by the United Nation General Assembly in September 2015 [3]. Less than a year

later the first Global Health Sector Strategy on Viral Hepatitis 2016-2021 was endorsed by the

World Health Assembly [4] and in September 2016, the European Action Plan for the Health Sector

Response to Viral Hepatitis in the 53 Member States of the WHO European Region was approved

during the WHO Regional Committee meeting in Copenhagen [5]. Both the Global Health Sector

Strategy and the European Action Plan recognises the need for robust national hepatitis strategic

information systems and urges Member States to have sound estimates of national prevalence

levels. Denmark has endorsed these international commitments and it is time to revise the national

estimates of both HBV and HCV prevalence.

Compared to HCV, the situation regarding HBV is slightly different: The 2007 estimate was 10-

16.000 chronic infections (0.24% of the adult populations) and

≥90% were born in high endemic

regions. The number of people in Denmark infected with chronic HBV is steadily increasing due to

immigration of people from endemic areas and Denmark is one of the few countries in the world

who have not included HBV vaccination in the routine childhood vaccination programme meaning

that there is an increased need for closely monitoring HBV in Denmark. For more than a decade, it

SUU, Alm.del - 2019-20 - Endeligt svar på spørgsmål 686: Spm. om oversendelse af forskningsprotokollen for det forskningsprojekt, der ligger til grund for, at det er muligt at opspore og behandle patienter med Hepatitis C, til sundheds- og ældreministeren

Nielsen et al:DKprevalence2017 version 20161208

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has been possible to treat (but not cure) chronic HBV infection. However, major advances in HBV

research are also happening and it is hoped that a cure for this infection will be available in the

coming decade. This treatment will likely be as costly as the DAA therapies for HCV and it is

therefore also important for Denmark to have valid and up-to-date national estimates for the total

number of people living with chronic HBV.

In the nearly ten years, since the collection of the data that was used to produce the most recent

national estimates for the number of people infected with chronic hepatitis in Denmark, several

important background factors affecting the transmission of viral hepatitis have changed

significantly: The immigration to Denmark of people from areas where viral hepatitis is endemic

has increased in the last ten years. And like in many other western European countries, data suggest

that the number of people who use drugs intravenously in Denmark has declined in the last ten

years [6]. Also, the screening of both HBV (among pregnant women) and HCV (among people who

use drugs) in Denmark has increased. Therefore, there is an urgent need to revise the national

estimates for HBV and HCV prevalence in Denmark.

Study aims:

To revise the national estimates of the number of people living in Denmark with chronic hepatitis B

and C based on the most recently available data.

We aim to evaluate if Denmark has been successful in reducing the undiagnosed fraction of people

with chronic hepatitis and to identify population groups and geographic areas where screening

should be improved.

Methods:

We plan to repeat the methodology that was used for the 2007 national HCV prevalence estimates:

A capture-recapture estimate based on multiple national registers using the Danish CPR-number as

identifier [1]. However, we will also explore the methods used in other countries who have recently

published revised national HCV prevalence estimates

–

for example the bayesian evidence

synthesis approach used for England [7] and the modified version of the Workbook Method which

has been applied in the Netherlands [8] to investigate if these might be applicable for Denmark. We

will also look into the approaches used to estimate national HCV and HBV prevalence in the USA

[9][10][11] and possibly other countries as well to ensure that we apply the most appropriate

methodology for the data available in Denmark.

Data sources

We will use the following data sources and extract data from the start of the register and until

31.12.2016. We will only include people living in Denmark with a valid civil registration (CPR)

number.



The laboratory database (DANVIR)

–

data on all patients testing positive for antiHCV and/or

HCVRNA as well aas patients positive for HBsAg and/or HBVDNA and antiHBcIgM

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

The clinical database (DANHEP)

–

data on all patients receiving specialised care for chronic

viral hepatitis

The communicable diseases register (Statens Serum Institut, SSI)

–

all notified cases of HBV

and HCV infection, including both acute and chronic cases

The Drug Treatment Register (SIB)

–

this database includes all patients treated for drug abuse in

Denmark. This data will be used to estimate the proportion of drug users who have been tested

for HCV and/or HBV

The national hospital register (LPR)

–

all patients discharged with hepatitis related diagnoses

(ICD10: B18.0, B18.1 or B18.2)

The national register of births (MFR)

–

all births since 01.01.2005. This information will be

used to estimate the proportion of the HBV population who is known.

The Civil Register (CPR)

–

for all patients/CPR-numbers included in the data extracted from

any of the above mentioned data sources, we want to have information on: vital status as of

31.12.2016 and migration status (measured by country of birth, nationality of the patient and

their parents).

Ethical approval

This study will be done as a register-based study and there will be no prospective contact with

individuals and no publication of data that can be linked to individuals. We will apply for approval

from the data protection authority in “Region Syd” of Denmark and data will be stored and handled

according to the national data protection act. As this is a register-based study, approval from the

national committee on health research ethics (DNVK) is not needed.

Planned outputs

The results of this study will be published in minimum two separate scientific papers in

international peer-reviewed journals. We will publish one paper with the HCV results (Stine

Nielsen will be first author and Peer Brehm Christensen will be last author on this publication) and

one paper with the HBV results (first and last authorship of this paper is not yet determined). On

both papers we propose the co-authors mentioned in the beginning of this document and other

members of DANHEP and DANVIR in acknowledgements

Budget

The costs of this study will include:

Extraction of data from the above mentioned sources

VIP salary

Travel, administration, data software etc.

30,000 DKK

150,000 DKK

30,000 DKK

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Total

210,000 DKK

Time plan

Data extraction and analysis should be done in first half of 2017. If possible, we hope to submit at

least one manuscript in late 2017 or latest in the first part of 2018.

References

1. Christensen P, Hay G, Jepsen P, Omland L, Just S, Krarup H, et al. Hepatitis C prevalence in

Denmark -an estimate based on multiple national registers. BMC Infect. Dis. [Internet].

2012;12:178. Available from: http://www.biomedcentral.com/1471-2334/12/178

2. Hansen, N; Hay, Gordon; Cowan, Susan; Jepsen, P; Bygum Krarup, H; Obel, N; Weis, N; Brehm

Christensen P. Hepatitis B prevalence in Denmark

–

an estimate based on nationwide registers and

a national screening programme, as on 31 December 2007. Eurosurveillance [Internet]. 2013;18.

Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20637

3. United Nations. Resolution adopted by the UN General Assembly on 25 September 2015

[Internet]. 2015. Available from:

http://www.un.org/ga/search/view_doc.asp?symbol=A/RES/70/1&Lang=E

4. WHO. Viral hepatitis 2016–2021. Glob. Hepat. Program. Dep. HIV/AIDS [Internet]. 2016;

Available from: http://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/

5. WHO Regional Committee for Europe. Action plan for the health sector response to viral

hepatitis in the WHO European Region 2017–2022. 2016;27. Available from:

http://www.euro.who.int/en/health-topics/communicable-

diseases/hepatitis/publications/2016/action-plan-for-the-health-sector-response-to-viral-hepatitis-in-

the-who-european-region.-draft-2016

6. Sundhedsstyrelsen. Narkotikasituationen i Danmark 2016 - Nationale data [Internet]. 2016.

Available from:

https://sst.dk/da/udgivelser/2016/~/media/07101779E7554638B36EEDBC00234590.ashx

7. Harris RJ, Ramsay M, Hope VD, Brant L, Hickman M, Foster GR, et al. Hepatitis C prevalence

in England remains low and varies by ethnicity : an updated evidence synthesis.

2011;22:187–92.

8. Vriend HJ, Van Veen MG, Prins M, Urbanus AT, Boot HJ, Op De Coul EL. Hepatitis C virus

prevalence in The Netherlands: migrants account for most infections. Epidemiol Infect [Internet].

2012/09/12. 2013;141:1310–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22963908

9. Klevens RM, Liu S, Roberts H, Jiles RB, Holmberg SD. Estimating Acute Viral Hepatitis

Infections From Nationally Reported Cases. Am. J. Public Health. 2014;104:482–7.

10. Chak E, Talal AH, Sherman KE, Schiff ER, Saab S. Hepatitis C virus infection

in USA : an

estimate of true prevalence. Liver Int. 2011;1090–101.

11. Edlin BR, Eckhardt BJ, Shu MA, Holmberg SD, Swan T. Toward a More Accurate Estimate of

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the Prevalence of Hepatitis C in the United States. Hepatology. 2015;