HEV Literature Systematic Review Methodology ECDC, 09/12/2015

1. Hepatitis E in EU/EEA countries: a systematic review of prevalence and incidence
Systematic review methodology
Ettore Severi, European Centre for Disease Prevention and Control
1st ECDC HEV expert meeting, Stockholm, 9/12/2015

2. Background
• Hepatitis E virus (HEV) infections in Europe more prevalent
than expected
• Increasing number of autochthonous hepatitis E (hep E) cases
in EU/EEA*
• High risk regions described in some EU/EEA countries
• Hep E not under EU-wide surveillance
• No harmonised case definition or reporting system at EU level
*EU/EEA: European Union / European Economic Area

3. Review objective
Describe the seroprevalence and the incidence of HEV infection
in EU/EEA by country and by sub-population group

4. Research question
What is the seroprevalence of HEV antibodies and the hepatitis
E incidence identified over the last 10 years (2005-recent) in
different populations surveyed in the EU/EEA by country
and/or region?

5. Search methodology
• Data sources
• Peer-reviewed literature in PubMed, Embase, Scopus, Cochrane Library
• Concepts of HEV with seroprevalence & incidence
• Controlled vocabulary (i.e. MeSH and Emtree terms) and
natural vocabulary (i.e. keywords)
• Time limit: 1 January 2005 – 27 August 2015
• Language limit: none
• Study population: only humans
• Geographical limit: none

6. Search strategy
Concept 1:
HEPATITIS
Concept 2:
SEROPREVALENCE
Concept 3:
SPECIES
Concept 4:
TIME LIMIT
OR OR
"hepatitis E"
hev
"Water Borne Hepatitides"
"Water Borne Hepatitis"
ahe
"ET NANBH"
ETNANBH
"Epidemic Non A, Non B Hepatitis"
"Epidemic Non A Non B Hepatitis"
"Enterically Transmitted Non A, Non B
Hepatitis"
"Enterically Transmitted Non A Non B
Hepatitis"
AND
inciden*
prevalen*
seropreval*
"sero prevalence"
"sero prevalences"
"sero prevalent"
seroepidemiolog*
"sero epidemiologic"
"sero epidemiological"
"sero epidemiology"
serosurvey*
"sero survey"
"sero surveys"
serolog*
epidemiolog*
seropositiv*
"sero positive"
"sero positivity"
seroimmun*
"sero immunology"
"sero immunological"
"sero immunologic"
occur*
frequent*
frequenc*
proportion*
rate*
time*
number*
percent*
AND
Humans
AND
From 2005

7. Literature selection
Step 1: title&abstract
• EndNote library exported to an excel file for review
• Articles were split in three groups by random order
• Initial piloting:
• First 150 randomly selected articles
• Review inclusion/exclusion criteria & exclusion categories
• Three reviewers reviewed all articles according to
inclusion/exclusion criteria
• Two reviewers reviewed each article
• Third reviewer reviewed those articles in disagreement

8. Inclusion criteria
• Population:
•all people living in EU/EEA countries (excluding overseas territories)
•general population including risk groups, blood donors, and other subgroups
• Exposure: HEV
• Outcome:
•HEV seropositive (HEV IgG/IgM) / anti-HEV antibody positive
•Hepatitis E report/notification/identification
• Study design: No restrictions
• Publication time frame: 1 January 2005 – 27 August 2015
• Language: All EU languages

9. Exclusion criteria
• Non-EU/EEA countries
• Case reports and case series with less than 10 cases
• Animal studies
• Vaccine studies
• Environmental analyses

10. Flowchart – step 1:
title&abstract screening
RECORDS RETRIEVED
634 records retrieved priorto deduplication
Medline (Pubmed):1568
Embase (embase.com): 2,529
Scopus (scopus.com): 865
Cochrane (cochrane.com): 16
Additional records identified through search
alerts:
2929 records after deduplication
EXCLUDED RECORDS
(Title/abstracts)
TOTAL: 2454 excluded
records
FULL PAPERS/REPORTS ORDERED
TOTAL: 475 records ordered
IDENTIFICATION
TITLE/ABSTRACT SCREENING

11. Flowchart – step 1:
title&abstract screening
RECORDS RETRIEVED
634 records retrieved priorto deduplication
Medline (Pubmed):1568
Embase (embase.com): 2,529
Scopus (scopus.com): 865
Cochrane (cochrane.com): 16
Additional records identified through search
alerts:
2929 records after deduplication
EXCLUDED RECORDS
(Title/abstracts)
TOTAL: 2454 excluded
records
FULL PAPERS/REPORTS ORDERED
TOTAL: 475 records ordered
IDENTIFICATION
TITLE/ABSTRACT SCREENING

12. Flowchart – step 1:
title&abstract screening
RECORDS RETRIEVED
634 records retrieved priorto deduplication
Medline (Pubmed):1568
Embase (embase.com): 2,529
Scopus (scopus.com): 865
Cochrane (cochrane.com): 16
Additional records identified through search
alerts:
2929 records after deduplication
EXCLUDED RECORDS
(Title/abstracts)
TOTAL: 2454 excluded
records
FULL PAPERS/REPORTS ORDERED
TOTAL: 475 records ordered
IDENTIFICATION
TITLE/ABSTRACT SCREENING

13. Flowchart – step 1:
title&abstract screening
RECORDS RETRIEVED
634 records retrieved priorto deduplication
Medline (Pubmed):1568
Embase (embase.com): 2,529
Scopus (scopus.com): 865
Cochrane (cochrane.com): 16
Additional records identified through search
alerts:
2929 records after deduplication
EXCLUDED RECORDS
(Title/abstracts)
TOTAL: 2454 excluded
records
FULL PAPERS/REPORTS ORDERED
TOTAL: 475 records ordered
IDENTIFICATION
TITLE/ABSTRACT SCREENING

14. • Articles for full text screening divided in two batches
• Two reviewers worked in parallel
• Additional support in house for articles not in English
• Articles included or excluded with same criteria as step 1
Literature selection
Step 2: full text

15. • Outsourced to Helmholtz Center for Infection Research
• Additional support in house for articles not in English
• Articles included or excluded with same criteria as step 1&2
Literature selection
Step 3: data extraction

16. Flowchart – step 2 & 3:
full text & data extraction screening
RECORDS RETRIEVED
634 records retrieved prior to deduplication
Medline (Pubmed):1568
Embase (embase.com): 2,529
Scopus (scopus.com): 865
Cochrane (cochrane.com): 16
Additional records identified through search
alerts:
2929 records after deduplication
EXCLUDED RECORDS
(Title/abstracts)
TOTAL: 2454 excluded
records
FULL PAPERS/REPORTS ORDERED
TOTAL: 475 records ordered
EXCLUDED RECORDS
(Full papers/reports)
NOT relevant XX
TOTAL: XX excluded records
INCLUDED STUDIES FOR DATA EXTRACTION
TOTAL: XXX
IDENTIFICATION
TITLE/ABSTRACT SCREENING
FULL PAPER/REPORT SCREENING FULL PAPERS/REPORTS ASSESSED
TOTAL: XXX records assessed
EXCLUDED RECORDS
X article non-EU languages
TOTAL: X excluded records
EXCLUDED RECORDS
(Full papers/reports)
Data not extractable XX
TOTAL: XX excluded recordsINCLUDED STUDIES AFTER DATA
EXTRACTION
TOTAL: XXX
DATA EXTRACTION SCREENING

17. • Data extraction tool and variable piloted by contractor
• Extraction to Excel by 2 experts independently
• Standardised format
• Separate databases for seroprevalence and incidence
• Unit of extraction is a “study”
• Each study provides seroprevalence or incidence data for
specific underlying population in defined study period and/or
geographical area
• Each article provide one or more studies
Data extraction -methods

18. • Seroprevalence database: age-stratified seroprevalence data
• Gender-stratified incidence and seroprevalence excluded (when
crude estimates available)
• Un-weighted data preferred to weighted data
• Output by the contractor:
• data in separated tabs
• one tab for each country
Data extraction –methods 2

19. • EU/EEA countries with available HEV seroprev/incidence data
• Study sample size and underlying populations
• Prevalence values for each country by population/region
• Prevalence values by age-groups (and years?)
• Study design
• Laboratory methods
• Geographical distribution of seroprevalence (map)
• Pooling of the data is not anticipated
Data synthesis

20. • Results may be hard to compare due to:
• different case definitions
• different testing methods
• various time points of testing
• Non representative subpopulations (too small numbers)
• Short study period (2005-2015), but:
• Rapid evolution in diagnostic systems
• older studies might not be comparable
Limitations

21. •Retrieved evidence for the specific macro-areas will be
analysed, summarised and described in an evidence report:
• according to the ECDC systematic review report template
• shared with the HEV expert group
• possibly shared with national FWD focal points
• published in the ECDC webpage
• Manuscript submitted to a peer-reviewed public health journal
Structured report

22. August 2015: EndNote library with search results
September 2015: pilot extraction criteria
September - November 2015: title&abstract screening
November - December 2015: full text screening
December 2015: evaluation of search results
December 2015 – May 2016: data extraction
June 2016: Review of extracted data
July - September 2016: data analysis and first draft of report
September - December 2016: First draft of manuscript
Timeline

23. Thanks for your attention
Any question?
http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/hepatitis-e