Monitoraggiodelle epatiti virali in EuropaPier Luigi LopalcoUniversità di Bari

Roma, 17 Dicembre 2015

Surveillance of hepatitis B and C in the EU/EEA

By courtesy of the Programme for HIV, STI and Viral Hepatitis B and C infections, ECDC

Surveillance of hepatitis B & C - Principles

• Surveillance programme coordinated by ECDC

• Data from 31 Member States are uploaded annually into the European Surveillance System (TESSy)

• Case-based and aggregate reporting possible

• Countries requested to follow the EU 2012 case definitions, including acute and newly diagnosed chronic infections

• Data collected on 33 variables

• Data validated by Member States

Surveillance of hepatitis B & C- Objectives

Epidemiological objectives

1. To monitor  the incidence and routes of transmission of newly diagnosed cases of hepatitis B and C in the general and vulnerable populations

2. To monitor the prevalence of chronic hepatitis B and C virus infection to determine burden of infection (and estimate the proportion undiagnosed) in the general and vulnerable populations

3. To monitor the proportion of chronic hepatitis B and C cases that are engaged in care (continuum of care)

4. To monitor the proportion of newly diagnosed chronic hepatitis B and C  presenting late

5. To determine genotype and sequence  distributions  of newly acquired hepatitis B and hepatitis C viruses to better follow transmission patterns, the emergence of resistance and vaccine escape mutants and  potentially more virulent virus strains (priority on hepatitis C infections)

6. To determine and describe the proportion of co‐infections (HIV/HBV/HCV/HDV)

7. To determine the proportion of HCV re‐infections  (especially among key risk groups with high incidence e.g. PWIDs)

To monitor:• Incidence• Prevalence• Route of transmission• Genotype and sequence distribution• Proportion of co‐infections• Proportion of HCV re‐infections

Surveillance of hepatitis B and C: data completeness in 2013

0 20 40 60 80 100

Genotype

HIV status

Complications

Sex worker

Probable country of infection

Country of birth

Country of nationality

Transmission

Health care worker

Testing location

Outcome

Imported

StageHEP

Gender

Age

Data completeness (%)

Hepatitis B

Hepatitis C

Hepatitis B data: reporting countries and case definitions28 countries provided hepatitis B data in 2013

• Six countries could only provide data on acute cases

Case definitions varied:• 18 countries used the EU 2012 case definition• Six countries used the EU 2008/EU 2002 case

definitions• Four countries used national case definitions

24 countries were able to classify cases as acute or chronic according to the EU 2012 case definition

Rate of reported acute hepatitis B cases in 2013*

*Data for UK exclude Scotland

Rate of reported chronic hepatitis B cases in 2013*

*Data for UK excludes Scotland

• In 2013, 19 101 cases* (4.4 cases per 100 000)– Acute: 2 896 (15%)– Chronic: 13 629 (71%)– Unknown: 2 138 (11%)

• Variation in numbers and rates between countries– Acute infections: from 0.1/100 000 in France and

Portugal to 4.3/100 000 in Latvia– Chronic infections: from 0.1/100 000 in Romania to

15.5 in Sweden

Hepatitis B data: reported cases, rates and stage of infection

*438 cases (2.3%) could not be classified by disease status due to incompatible format of the data provided

Rate of acute and chronic hepatitis B cases in EU/EEA countries, 2006-2013

Source: country reports; Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Latvia, Lithuania, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom (excluding Scotland).

0,1

1,0

10,0

2006 2007 2008 2009 2010 2011 2012 2013

Rate per 100

 000

Logarithmic scale

Acute

Chronic

Hepatitis B by age and disease status:rate of reported cases per 100 000, 2013

Source: Country reports; Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Netherlands, Norway, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom (excluding Scotland).

0

5

10

15

20

25

30

<5 5–14 15–19 20–24 25–34 35–44 45–54 55–64 ≥65

Rat

e pe

r 10

0 00

0

Age group (years)

Acute

Chronic

35%

15%

M:F = 1.5:1

Reported transmission category for acute and chronic hepatitis B cases, 2013

Source: Country reports; Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Netherlands, Norway, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom (excluding Scotland).

0 10 20 30 40 50

Heterosexual transmission

Nosocomial (includes hospital, nursing home, etc.)

Injecting drug use

Men who have sex with men (MSM)

Non‐occupational injuries (needle stick, bites, tattoos, piercings)

Other

Sexual transmission (not specified)

Household

Blood and blood products

Mother‐to‐child transmission

Needle‐stick and other occupational exposure

Haemodialysis

Organ and tissues

Proportion of cases (%) 

Tran

smission

 category

Acute

Chronic

Migration variables poorly reported but 50% of cases with complete information were classified as ‘imported’

Hepatitis C data: reporting countries and case definitions26 countries provided hepatitis C data in 2013

• Four countries could only provide data on acute cases

Case definitions varied:• 14 countries used the revised EU case definition• Seven countries used the EU 2008 case definition• Five countries used national case definitions

17 countries were able to classify cases as acute or chronicAccording to the EU 2012 case definition

Hepatitis C data: reported cases, rates and stage of infection

• In 2013, 31 513 hepatitis C cases* were notified representing a rate of 9.6 cases per 100 000:– 569 (2%) Acute– 4 776 (15%) Chronic– 23 230 (74%) Unknown**

• Variation in overall numbers and rates between countries– Acute infections: rates from <0.1/100 000 in Portugal

and Greece to 2.6/100 000 in Latvia– Chronic infections: rates from 0.1/100 000 in Romania

to 60.1/100 000 in Latvia

**As acute hepatitis C is difficult to diagnose clinically or serologically, most ‘unknown’ cases are likely to be chronic infections.

*2 938 cases (9%) could not be classified by disease status due to incompatible format of the data provided

Rate of all reported hepatitis C cases across EU/EEA countries, 2006-2013

Source: country reports; Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom.

0

2

4

6

8

10

12

2006 2007 2008 2009 2010 2011 2012 2013

Rate per 100

 000

Rate of reported hepatitis C cases in 2013 (including acute, chronic and unknown stage)*

*Countries included if their surveillance systems captured data on both acute and chronic cases..

Rate of reported hepatitis C cases per 100 000 by age and gender, 2013 (includes acute, chronic and unknown stage)

Source: Country reports: Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Norway, Portugal, Romania, Slovakia, Slovenia, Sweden, United Kingdom.

0

5

10

15

20

25

30

35

<5 5–14 15–19 20–24 25–34 35–44 45–54 55–64 ≥65

Rat

e pe

r 10

0 00

0

Age group (years)

Male

Female9%

M:F = 1.9:1

54%

Reported transmission category for acute and chronic hepatitis C cases in 2013

Source: Country reports; Austria, Cyprus, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Norway, Portugal, Romania, Slovakia, Slovenia, Sweden, United Kingdom.

0 20 40 60 80 100

Injecting drug use

Blood and blood products

Sexual transmission (not specified)

Heterosexual transmission

Other

Nosocomial (includes hospital, nursing home, etc.)

Non‐occupational injuries (needle stick, bites, tattoos, piercings)

Needle‐stick and other occupational exposure

Mother‐to‐child transmission

Haemodialysis

Household

Men who have sex with men (MSM)

Organ and tissues

Proportion of cases (%) 

Tran

smission

 category

Acute

Chronic

9% of cases with complete information were classified as ‘imported’

Summary of key findings

• High numbers of newly diagnosed hepatitis B and C cases notified across Europe– Hepatitis C rate is more than twice the hepatitis B rate – Chronic cases dominate across both diseases – Marked variation between countries

• Hepatitis B:– a decrease in acute cases – a rise in newly reported chronic infections

• Hepatitis C: strong geographical trend affected by different testing practices across Europe

• Transmission routes for hepatitis B differ from hepatitis C, and for hepatitis B these routes vary by disease status

• Imported cases are significant, especially for hepatitis B

Key limitations of the data

• Different case definitions used by countries• Some countries still only report acute hepatitis cases• Difficulties with ascertaining stage of diseases according to

case definition– High proportion of cases coded as unknown particularly

for Hepatitis C– Some countries use their own criteria

• Data completeness low for certain variables:– Genotype, complications, country of nationality, HCV

status (for HBV cases), HBV status (for HCV cases), HIV status, sex worker, healthcare worker

• Under-reporting major issue reported by some countries• Due to the largely asymptomatic nature of hepatitis

infections, data are strongly related to local testing practices

Acknowledgements

Thank you to the following groups and individuals:• The European Hepatitis B and C Network and Coordination

Committee.• EU/EEA country hepatitis and surveillance contact points.• Surveillance colleagues at ECDC: Catalin Albu, Julien

Beauté, Denis Coulombier, Catia Cunha, Gaetan Guyodo, Frantiska Hruba, Valentina Lazdina, Klaus Weist, Phillip Zucs.

• Colleagues in the programme on HIV/AIDS, STI and Viral Hepatitis B and C: Andrew Amato-Gauci, Caroline Daamen, Gianfranco Spiteri.

A time machine to prevent HAV outbreaks in the EU

Hepatitis A global endemicity levels and implication for vaccination strategy

• WHO estimates the level of endemicity based on the anti-HAV seroprevalence.

• WHO recommends no vaccination in high endemicity areas, universal vaccination in intermediate endemicity areas and at-risk group vaccination in low and very low endemicity areas

Source:  KH Jacobsen et al. Vaccine 2010WHO position paper on hepatitis A vaccines – June 2012

Hepatitis A global endemicity levels and implication for vaccination strategy

Source:  KH Jacobsen et al. Vaccine 2010WHO position paper on hepatitis A vaccines – June 2012

Novel risk factors for HAV infection

- 2nd generation migrants visiting country of origin- New parents of adoptees from endemic countries

- Foodborne transmission

2013/2014 HAV infection outbreaks

HAV outbreak Declared Genotype Associated 

casesVehicle of infection

Nordic Countries March 2013 IB 77 confirmed 

40 probableFrozen 

strawberries

EU Ex‐Egypt April 2013 IB 21 confirmed 86 probable 

Freshstrawberries

U.S.A May 2013 IB 167 confirmed Pomegranates

Multinational EU May 2013 IA 270 confirmed 

1200 probable  Frozen berries

Systematic review: PRISMA flowchart

Records identified through database searching  

n =4465Screen

ing 

Includ

ed 

Eligibility 

Iden

tification 

Additional records identified through other sources  

n =81 

Records after duplicates removed n =4276 

Records screened n =432  

Records excludedn =3844

Full‐text articles assessed for eligibility  

n =432

Full‐text articles excluded n = 110‐Non HAV: 3 ‐Non prevalence: 68 ‐Non general population: 19 ‐Not found/other: 20

Eligible studies for data extraction n =322

Not abstractable datan =94 

Included studies n = 228

Records identified through database searching  

n =4465Screen

ing 

Includ

ed 

Eligibility 

Iden

tification 

Additional records identified through other sources  

n =81 

Records after duplicates removed n =4276 

Records screened n =432  

Records excludedn =3844

Full‐text articles assessed for eligibility  

n =432

Full‐text articles excluded n = 110‐Non HAV: 3 ‐Non prevalence: 68 ‐Non general population: 19 ‐Not found/other: 20

Eligible studies for data extraction n =322

Not abstractable datan =94 

Included studies n = 228

Definitions

Risk of infection among adults >30 years

Seroprevalence levels *

* World Health Organization. WHO position paper on hepatitis A vaccine‐June 2012. WER 2012; 28‐29: 261‐276. Available at: http://www.who.int/wer/2012/wer8728_29.pdf?ua=1

Temporal evolution of anti-HAV seroprevalence by country, 1975-2013

Quality score: 0 (non randomized sample and n<500); 1 (randomized sample or n≥500); 2 (randomized sample and n≥500)

Case-study PortugalSummary of anti-HAV seroprevalence in Portugal, by age group, 1983-2012

Temporal evolution of hepatitis A seroprevalence by country

Quality score: 0 (non randomized sample and n<500); 1 (randomized sample or n≥500); 2 (randomized sample and n≥500)

Case-study GermanySummary of seroprevalence in Germany, by age and time period

Hepatitis A seroprevalence profile in the EU/EEA, 2000-2013

No dataVery lowLowIntermediate

HAV seroprevalence profiles

Seroprevalence classification  Assessment criteria: HAV seroprevalence

Very low <50% by age 30 yearsLow ≥50% by age 30 years, with <50% by age 15

Seroprevalence classification  Assessment criteria: HAV seroprevalenceIntermediate ≥50% by age 15 years, with <90% by age 10 yearsHigh ≥90% by age 15 years

Hepatitis A susceptibility in adults in the EU/EEA, 2000-2013

No dataLowModerateHighVery high

HAV susceptibility profiles

Susceptibility classification  Assessment criteria: HAV susceptibilityVery high >70% at 30 years; and >50% at 50 yearsHigh 50‐70% at 30 years; and 30‐50% at 50 years

Susceptibility classification  Assessment criteria: Moderate 30‐50% at 30 years; and <30% at 50 yearsLow <30% at 30 and 50 years

Human Development Index 2013

Temporal evolution of susceptibility to hepatitis A in the EU/EEA, 1975-2013

Acknowledgement

ECDCSandro Bonfigli

Paloma Carrillo

Pierluigi Lopalco

Ettore Severi

Johanna Takkinen

Emma Bystrom

ECDC LibraryAna-Belen Escriva

Irene Munoz Guajardo

EPIET fellowMichael Edelstein

All ECDC colleagues that helped with translation of articles

Member States focal points for food- and water-borne and for vaccine preventable diseases

Expert panel membersRoman Chilbek, Czech Republic

Angela Dominguez, Spain

Caterina Rizzo, Italy

Manolis Galanakis, Greece

Denisa Janta, Romania

Mira Kojouharova, Bulgaria

Jördis Ott, Germany

Noel Nelson, United States

Daniel Shouval, Israel

Ingrid Uhnoo, Sweden

Vytauthas Usonis, Lithuania

Grazie per l’attenzione