hev systematic review - 1st ecdc hev meeting

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

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

2

*EU/EEA: European Union / European Economic Area

Review objective

Describe the seroprevalence and the incidence of HEV infectionin EU/EEA by country and by sub-population group

3

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?

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

5

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

Literature selectionStep 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

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

Exclusion criteria

• Non-EU/EEA countries

• Case reports and case series with less than 10 cases

• Animal studies

• Vaccine studies

• Environmental analyses

Flowchart – step 1:title&abstract screening

RECORDS RETRIEVED 634 records retrieved prior to deduplication

Medline (Pubmed):1568Embase (embase.com): 2,529Scopus (scopus.com): 865Cochrane (cochrane.com): 16Additional 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

• 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 selectionStep 2: full text

• 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 selectionStep 3: data extraction

Flowchart – step 2 & 3:full text & data extraction screening

RECORDS RETRIEVED 634 records retrieved prior to deduplication

Medline (Pubmed):1568Embase (embase.com): 2,529Scopus (scopus.com): 865Cochrane (cochrane.com): 16Additional records identified through search alerts:

2929 records after deduplicationEXCLUDED RECORDS

(Title/abstracts)TOTAL: 2454 excluded

records

FULL PAPERS/REPORTS ORDERED TOTAL: 475 records ordered

EXCLUDED RECORDS(Full papers/reports)

NOT relevant XXTOTAL: XX excluded records

INCLUDED STUDIES FOR DATA EXTRACTIONTOTAL: XXX

IDENTIFICATION

TITLE/ABSTRACT SCREENING

FULL PAPER/REPORT SCREENING FULL PAPERS/REPORTS ASSESSEDTOTAL: XXX records assessed

EXCLUDED RECORDSX article non-EU languagesTOTAL: X excluded records

EXCLUDED RECORDS(Full papers/reports)

Data not extractable XXTOTAL: XX excluded recordsINCLUDED STUDIES AFTER DATA

EXTRACTION

TOTAL: XXX

DATA EXTRACTION SCREENING

• 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

• 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

• 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

• 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

•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

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

Thanks for your attention

Any question?

http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/hepatitis-e

hev systematic review - 1st ecdc hev meeting

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