The Decline of Hepatitis B Virus Infection in the Kingdom ... · PDF fileThe Decline of Hepatitis B Virus Infection in the Kingdom of Saudi Arabia. ... Epidemiology of HBV in Saudi

The Decline of Hepatitis B Virus Infection The Decline of Hepatitis B Virus Infection in the Kingdom of Saudi Arabiain the Kingdom of Saudi Arabia

Professor Banji Ayoola MD FACPProfessor Banji Ayoola MD FACPChief of HepatogastroenterologyChief of HepatogastroenterologyKing Fahad Central HospitalKing Fahad Central HospitalGizan Saudi ArabiaGizan Saudi Arabia

AgendaAgenda……..

•• Summary of the epidemiology of HBV in Saudi ArabiaSummary of the epidemiology of HBV in Saudi Arabia

•• Hepatitis B vaccination: Integration into EPI and initial Hepatitis B vaccination: Integration into EPI and initial evaluationevaluation

•• Assessment of the impact on the prevalence of HBV markers in Assessment of the impact on the prevalence of HBV markers in childrenchildren

•• Changing epidemiology of HBV in unvaccinated adult populationChanging epidemiology of HBV in unvaccinated adult population

•• Ultimate goal: Reduction of HBV Ultimate goal: Reduction of HBV ––related liver diseasesrelated liver diseases

•• ConclusionsConclusions

Saudi Arabia …..

N

W

S.W

C

E

Middle Eastern Country:Middle Eastern Country:Arabian Peninsula; Arabian Peninsula; on the Red seaon the Red sea

Population:Population:1991 1991 –– 10 million10 million2001 2001 –– 16 million16 million> 50% younger than 40y> 50% younger than 40y

HHomogeneous omogeneous culture /religionculture /religion

Free health care within a national Free health care within a national systemsystem

EconomicEconomic status: High GNPstatus: High GNP

Rapid Rapid Education and Social Education and Social developmentdevelopment

Epidemiology of HBV in Saudi ArabiaEpidemiology of HBV in Saudi Arabia

•• HBV is endemic in Saudi ArabiaHBV is endemic in Saudi Arabia

–– In apparently healthy adults, In apparently healthy adults, 7 7 -- 8% are HBsAg 8% are HBsAg ““carrierscarriers””;; At least At least one marker is positive in one marker is positive in 60 60 --70% of the population70% of the population

–– In children: HBsAg In children: HBsAg 6.7%;6.7%; any marker any marker 20%20%

•• Characteristics Characteristics –– Horizontal transmission; Acquisition during early lifeHorizontal transmission; Acquisition during early life–– Regional variations in prevalence of HBsAg in asymptomatic persoRegional variations in prevalence of HBsAg in asymptomatic personsns

•• Chronic HBV infectionChronic HBV infection : a major cause of acute hepatitis, liver : a major cause of acute hepatitis, liver cirrhosis and hepatocellular carcinoma [HCC]cirrhosis and hepatocellular carcinoma [HCC]

Regional variation in the prevalence of HBV in Saudi Arabia [pooled data from surveys up to 1988]

5.5%

8.9%

7.6%

0 1 2 3 4 5 6 7 8 9 10

Central

South west

Eastern

Regional variation in the prevalence of HBsAg Regional variation in the prevalence of HBsAg

in Saudi Arabia. in Saudi Arabia.

Males FemalesProvinces no tested % pos no tested % pos

Central 2155 6.9 4494 4.1

South west 1593 13.8 5642 3.9

Eastern 7838 11 462 8.2

**FalehFaleh 19881988[pooled data]*[pooled data]*

HBV markers [presence of any marker] in male blood donors [BD] and pregnant females [PF] in

the 1980's

38.3

49.7

58.7

37.4

0

10

20

30

40

50

60

70

Gizan PF Riyadh PF Gizan BD Riyadh BD

Base Base –– line;line; community community –– based survey in Saudi children [1989based survey in Saudi children [1989]] Cluster sampling of 4575 children [2458 males and 2117 femalesCluster sampling of 4575 children [2458 males and 2117 females; age < 10y] ; age < 10y] Urban (n = 2225) and Rural (n =2350) Urban (n = 2225) and Rural (n =2350)

6.7

3

5.8

4.2

HBsAg

Anti - HBc

Anti- HBs

AntiHBc+AntiHBs

6.7%

80.3

19.7

No marker

Any marker

HBsAg in Saudi children in 1989

0123456789

10

1 2 3 4 5 6 7 8 9 10

HBsAg%

Age in years

0

2

4

6

8

10

12

14

Tabuk Asir Najran Hail taif Jeddah

Regional variation in the prevalence of HBsAg among Saudi children [1989]:

1989

North SW Central West East

Profile of HBV markers in Saudi children [1989 survey]Profile of HBV markers in Saudi children [1989 survey]

7.3

3.3

5.1

3

6.1

3.8

4.9

2.5

6.8

5.3

7.3

4.1

0

5

10

15

20

25

y1 - 3 y4 - 6 y7 -10

Anti - HBc +anti HBsAnti - HBsAnti - HBcHBsAg

HBsAg in Saudi children [1989]HBsAg in Saudi children [1989]

Socio Socio –– economic classeconomic classUpperUpper [80 of 1071] [80 of 1071] 7.5% 7.5% Middle Middle [92 of 1541][92 of 1541] 6.0%6.0%Lower Lower [133 of 1911][133 of 1911] 7.0%7.0%

Family sizeFamily sizeSmall [1 Small [1 --5]5] [n = 2102][n = 2102] 6.0%6.0%Medium [6 Medium [6 --10]10] [n = 1983][n = 1983] 7.2%7.2%Large [>10]Large [>10] [n = 292][n = 292] 8.2%8.2%

HBV profile in Saudi children [1989]HBV profile in Saudi children [1989]Gender Residency

0

5

10

15

20

25

HBsAg Anymarker

MaleFemale

n. s.

0

5

10

15

20

25

HBsAg Anymarker

UrbanRural

P= 0.02

P= 0.007

HBeAgHBeAg in HBsAg in HBsAg -- positive Saudi children : positive Saudi children : The The status in 1989status in 1989

55, 18%

252, 82%HBeAgNo HBeAg


•• Overview of the epidemiology of HBV in Saudi ArabiaOverview of the epidemiology of HBV in Saudi Arabia


•• Assessment of the impact on the prevalence of HBV markers in chiAssessment of the impact on the prevalence of HBV markers in childrenldren

•• Changing epidemiology of HBV in unvaccinated populationChanging epidemiology of HBV in unvaccinated population

•• Current role of HBV in liver diseases in Gizan Current role of HBV in liver diseases in Gizan

•• Conclusions and thoughtsConclusions and thoughts

In 1989,HB vaccine was integrated into the EPI In 1989,HB vaccine was integrated into the EPI [as the 7[as the 7thth immunogen]immunogen]

The goal of the programThe goal of the programwas to reduce the prevalence of chronic HBV infection, was to reduce the prevalence of chronic HBV infection, thereby reducing the reservoir of HBVthereby reducing the reservoir of HBVand cause a decline in the incidence and prevalence of HBV and cause a decline in the incidence and prevalence of HBV –– related diseasesrelated diseases

•• MandatoryMandatory–– All newborns [0 All newborns [0 --1y]1y] 19891989–– Children at school entry[6 Children at school entry[6 --7y]7y] 19901990

•• VoluntaryVoluntary–– ““Pre Pre ––schoolersschoolers”” [1 [1 --5]5] 1990/19911990/1991–– Health personnel [adults]Health personnel [adults] 19901990–– OthersOthers 19891989

All Saudi citizens < 18y should have been vaccinated by the yearAll Saudi citizens < 18y should have been vaccinated by the year 20022002

Evaluation of Hepatitis B vaccination program 2 Evaluation of Hepatitis B vaccination program 2 years after the commencement of the program:years after the commencement of the program:

•• Coverage Coverage –– In the first year [1In the first year [1stst dose 90%; 3dose 90%; 3rdrd dose 73%]dose 73%]–– In the second year [1In the second year [1stst dose 95%; 3dose 95%; 3rdrd dose 90%]dose 90%]

•• SeroSero --conversion study:conversion study:–– 637 vaccinated children637 vaccinated children [aged 1 and 2 y] compared with[aged 1 and 2 y] compared with–– 617 unvaccinated children617 unvaccinated children [similar age group] [similar age group] –– from 5 regions of different HBV endemicityfrom 5 regions of different HBV endemicity

–– HighHigh [[TaboukTabouk, Gizan] , Gizan] MediumMedium [Riyadh] [Riyadh] LowLow [Hail, [Hail, GassimGassim]]

Response to Hepatitis B vaccination in Saudi infantsResponse to Hepatitis B vaccination in Saudi infants

93%93%138/147138/147QassimQassim

94%94%187/200187/200RiyadhRiyadh

98%98%118/120118/120HailHail

97%97%103/106103/106TaboukTabouk

89%89%57/6457/64GizanGizan

% anti% anti-- HBs positiveHBs positiveNo. pos/testedNo. pos/testedRegionsRegions

Anti HBs in children vaccinated against HBVAnti HBs in children vaccinated against HBV

7.1

16.2

22.6

54.2

0

20

40

60

80

100

120

>10050 to 9910 to 49<10

mIU/mL

Comparison of the HBV profile between vaccinated and Comparison of the HBV profile between vaccinated and unvaccinated childrenunvaccinated children

617617637637No testedNo tested

2.1%2.1%0%0%Anti Anti –– HBs & anti HBcHBs & anti HBc

3.1%3.1%0.02%0.02%Anti HBc +Anti HBc +

8.3%8.3%0%0%HBsAg +HBsAg +

5.3%5.3%94%94%Anti HBs +Anti HBs +

UnvaccinatedUnvaccinatedVaccinatedVaccinated

Efficacy 99.1%




•• Assessment of the impact on the prevalence of HBV Assessment of the impact on the prevalence of HBV markers in childrenmarkers in children

•• Changing epidemiology of HBV in unvaccinated populationChanging epidemiology of HBV in unvaccinated population

•• Current role of HBV in liver diseases in GizanCurrent role of HBV in liver diseases in Gizan


In 1997 a national survey was repeatedIn 1997 a national survey was repeated

…….. to determine whether the prevalence .. to determine whether the prevalence of HBV had declined among Saudi children, of HBV had declined among Saudi children, 8 years after the integration of HB vaccine 8 years after the integration of HB vaccine

into the national EPIinto the national EPI

No of children = 5355No of children = 5355

J Infect 1999; 38: 167

Prevalence of HBsAgPrevalence of HBsAg…….. 8 years after.. 8 years after

6.7

0.30

1

2

3

4

5

6

7

1989 1997

19891997

N = 4575

N = 5355

07.5taif 0.33.7jeddah 0.43.1dammam0.412.6tabuk

09Al jouf05.2Najran

0.78.8Jizan07.9Al-baha

1.510.2Asir05.7Mekkah

0.85.8Medina02.8Hail

0.53.4Gassim08.6Riyadh

19971989HBsAg prevalence in Saudi children declined in all areas of the country

Decline in the prevalence of HBsAg in Saudi children in differenDecline in the prevalence of HBsAg in Saudi children in different regionst regions

0

2

4

6

8

10

12

14

Riyadh

Gassim Hail

Medina

Al jouf

tabuk

dammam

jeddah

taif

Makka

h

AsirAl-b

aha

Jizan

Najran

1989

1997

Central North West South West

%

Age Age –– related prevalence of HBsAg: 1989 vs. 1997related prevalence of HBsAg: 1989 vs. 1997

0123456789

10

1 2 3 4 5 6 7 8 9 10

19971989

% positive

Age in years

Decline of Decline of antianti-- HBcHBc among children 8 years after among children 8 years after vaccination programvaccination program

4.2

0.46

00.5

11.5

22.5

33.5

44.5

1989 1997

19891997

Decreased prevalence of anti Decreased prevalence of anti –– HBc in childrenHBc in children

0

1

2

3

4

5

6

7

1----2 3----4 5----6 7----8 9----10

1989

1997

Age

%

What about the other viruses?What about the other viruses?

•• HAVHAV

•• HCVHCV

The decline of HBsAg among children in the South The decline of HBsAg among children in the South -- Western region: 8 Western region: 8 years after commencement of HB Vaccination programyears after commencement of HB Vaccination program

50.379.10005.2Najran

828005.60.78.8Jizan

22.140.600.707.9Al-baha

1944.500.41.510.2Asir

199719891997198919971989

Anti - HAVAnti - HCVHBsAg

C/f HCV and HAV

The decline of HBsAg among children in the Central region:The decline of HBsAg among children in the Central region:8 years after commencement of HB Vaccination program8 years after commencement of HB Vaccination program

28.259.5000.85.8Medina

20.4560002.8Hail

31.662.7000.53.4Gassim

16390.10.808.6Riyadh

199719891997198919971989

Anti - HAVAnti - HCVHBsAg

HBV as a cause of acute hepatitis in children and HBV as a cause of acute hepatitis in children and adults 10 years after universal vaccination [1999]adults 10 years after universal vaccination [1999]

6.1

57.3

0.7

30.926.2

11.9

35.6

6.8 4.10

10

20

30

40

50

60

<10 10 -20y >21

HBVHAVHCV

%

N =73N = 131 N = 42

Successful Integration of HB vaccine Successful Integration of HB vaccine into the National EPIinto the National EPI

•• Strong national policyStrong national policy•• Funds and fundingFunds and funding•• Effective EPI systemEffective EPI system•• ““ExternalExternal”” monitoring and auditingmonitoring and auditing




•• Assessment of the impact on the prevalence of HBV markers in Assessment of the impact on the prevalence of HBV markers in childrenchildren

•• Changing epidemiology of HBV in unvaccinated Changing epidemiology of HBV in unvaccinated populationpopulation

• Current role of HBV in liver diseases in Gizan


Trend in Saudi adults: Studies in Trend in Saudi adults: Studies in Gizan, South Gizan, South –– Western regionWestern region

The south The south –– western regions, particularly Gizan Had western regions, particularly Gizan Had very high prevalence rates of HBV infectionvery high prevalence rates of HBV infection

Cross Cross –– sectional studies in 1985 and 1986sectional studies in 1985 and 1986…….. 12% .. 12% to 32% in to 32% in ““healthyhealthy”” persons were HBsAg positive.persons were HBsAg positive.

In 1992 and 1997 we conducted community In 1992 and 1997 we conducted community ––based studies with larger number of subjectsbased studies with larger number of subjects

HBV and HCV in Gizan, Saudi Arabia [1992]HBV and HCV in Gizan, Saudi Arabia [1992]

Anti Anti -- HCV HCV

•• Males ... 2.3 % Males ... 2.3 % [n=705] [n=705]

•• Females 1.4 % Females 1.4 % [n=777][n=777]

•• All........ 1.8 % All........ 1.8 % [n=1482][n=1482]

HBsAgHBsAg

•• Males ..... 9 .4% Males ..... 9 .4% [n=371][n=371]

•• Females ... 6 .1% Females ... 6 .1% [n=424][n=424]

•• All ........... 7 .7% All ........... 7 .7% [n=795][n=795]

Faleh/Ayoola et al

Prevalence of HBsAg and antiPrevalence of HBsAg and anti--HCV among adult HCV among adult populations of the Gizan region of Saudi Arabia [1992]populations of the Gizan region of Saudi Arabia [1992]

02468

10121416

20-29

30- 3

940

- 49

50+

20-29

30-39

40-49 50

+

HBsAgAnti-HCV

%

Males Males Females Females FalehFaleh..and Ayoola et al..and Ayoola et al

Prevalence of HBV [any marker] in South Prevalence of HBV [any marker] in South -- Western Region of Western Region of Saudi Arabia Saudi Arabia [1992][1992]

0

10

20

30

40

50

60

2nd 3rd 4th 5th 6th all

malefemaleboth

Age groups in decadesAge groups in decades

% any % any markermarker

Further studies in Gizan 1995 to 1998 Further studies in Gizan 1995 to 1998

•• Blood donors [14883 males] tested June 1995 to June Blood donors [14883 males] tested June 1995 to June 19971997–– HBsAg 5.4%HBsAg 5.4%

•• Subjects [males and females ] from community [ n = 1172] Subjects [males and females ] from community [ n = 1172] in 1997in 1997–– HBsAg = 5.1HBsAg = 5.1%%

•• Hospitalized patients [n = 4692] from June 1995 to June Hospitalized patients [n = 4692] from June 1995 to June 19961996–– HBsAg = 9.4%HBsAg = 9.4%

•• Children [<10y; n = 229] in 1997/98Children [<10y; n = 229] in 1997/98–– HBsAg = 0.9% [2 children]HBsAg = 0.9% [2 children]

Ayoola et al SMJ 2003

HBsAg in Gizan adults [1997]

012345678

11 - 20y 21 - 30y 31 -40y >41yAge

%

Males

Females

Prevalence of HBsAg in the Gizan region of Saudi Arabia: Prevalence of HBsAg in the Gizan region of Saudi Arabia:

Analysis of blood donors [n=6927] and patients [n = 4692]Analysis of blood donors [n=6927] and patients [n = 4692]

0

2

4

6

8

10

12

14

16

Jun-95

Jul-95

Aug-95

Sep-95

Oct-95

Nov-95

Dec-95

Jan-96

Feb-96

Mar-96

Apr-96

May-96

Jun-96

Months

Per c

ent p

ositi

ve

Blood donorsPatients

The decline of HBV in the apparently healthypopulation of Gizan

1985 [1985 [AryaArya] ] 1992[Faleh] 1992[Faleh] 1997 [ Ayoola ]1997 [ Ayoola ]

Males Males 57/286 [19.9%] 57/286 [19.9%] 35/371 [9.4%]35/371 [9.4%] 23/398 [5.8%] 23/398 [5.8%]

Females Females 34/366 [9.3%] 34/366 [9.3%] 26/424 [6.1%] 26/424 [6.1%] 13/306 [4.2%]13/306 [4.2%]

AllAll 91/652 [13.9%] 91/652 [13.9%] 61/795 [7.7%]61/795 [7.7%] 36/704 [5.1%]36/704 [5.1%]

Trend in the prevalence of HBsAg in Trend in the prevalence of HBsAg in asymptomatic Saudi adults in Gizanasymptomatic Saudi adults in Gizan

13.9

7.15.1 3.2

0

2

4

6

8

10

12

14

1985 1992 1997 2003

Arya et alFaleh et alAyoola et alUnpublished

N= 705N = 652 N =795

0

5

10

15

20

25

30

35

40

45

50

% pos.

HBsAg anti -HBs/antiHBc

anti-HBc only anti -HBs only Any marker

HBV markers

HBV markers in Gizan, Saudi Arabia: Comparison of rates in adults [1985 and 1997]

Similar trend in other regions Similar trend in other regions ……....

11.9

6.7

0

2

4

6

8

10

12

% HBsAg positive

1980 - 1984 [n=4712 1985 - 1997 [n=97580

Decline of HBsAg prevalence in the Eastern Region of Saudi Arabia

4.7

3

1.4

1.971.7

1.2

1.7

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

%

y1987 y1991 y1996 y1997 y1998 y1999 y2000

Central region: HBsAg in Riyadh blood donors

Faleh et al 2004 Fathala et al



•• Hepatitis B vaccination: Integration into EPI and initial evaluHepatitis B vaccination: Integration into EPI and initial evaluationation





HBV and liver diseasesHBV and liver diseasesThe ultimate goal of preventive intervention is The ultimate goal of preventive intervention is to reduce the incidence and prevalence of to reduce the incidence and prevalence of

Chronic carriage of HBVChronic carriage of HBVAcute hepatitisAcute hepatitisChronic hepatitis andChronic hepatitis and Liver cirrhosisLiver cirrhosisHepatocellular carcinomaHepatocellular carcinoma

Etiology of Viral HepatitisEtiology of Viral Hepatitis

in Gizanin Gizan In Riyadh

HAV[38.3%]

HBV[12.8%HCV[n=20.3]

NABC[26.3%]OTHERS[2.3%]

non A - E 24 %HAV

38%

Dual2%

HEV13%

HCV4%

HBV19%

Arif et al 1998Ayoola et al SJG 2001

The role of HBV and HCV in The role of HBV and HCV in hepatocellular carcinoma [HCC] in Saudi hepatocellular carcinoma [HCC] in Saudi

ArabiaArabia

Case Case –– control study 1997 control study 1997 --19981998

Ayoola et al JGH 2004Ayoola et al JGH 2004

50% improvement in health indicators in a community 50% improvement in health indicators in a community can be attributed to EDUCATION [WHO]can be attributed to EDUCATION [WHO]

•• Literacy rates in Saudi populationLiteracy rates in Saudi population–– 1950 1950 --60 < 20%60 < 20%–– 1970 : 40 1970 : 40 --50%50%–– 1990: 1990: 80 80 --90%90%

•• Socio Socio –– economic progresseconomic progress–– HousingHousing–– SanitationSanitation–– AwarenessAwareness



•• Hepatitis B vaccination: Integration into EPI and initial evaluHepatitis B vaccination: Integration into EPI and initial evaluationation





Hepatitis B vaccination exerted the Hepatitis B vaccination exerted the greatest impact on HBV infection in greatest impact on HBV infection in Saudi ArabiaSaudi Arabia

Summary and conclusionsSummary and conclusions

•• HBV was endemic in Saudi ArabiaHBV was endemic in Saudi Arabia

•• Major reduction in HBV infection and its transmission has Major reduction in HBV infection and its transmission has occurred as a result of the universal HB vaccinationoccurred as a result of the universal HB vaccination

•• A secondary effect of HB vaccination most likely, contributed A secondary effect of HB vaccination most likely, contributed to to the decline of the HBV prevalence observed among largely the decline of the HBV prevalence observed among largely unvaccinated adult populationunvaccinated adult population

•• Do we need booster dose?Do we need booster dose?–– Preliminary analysis of children [14 Preliminary analysis of children [14 –– 15 y] and [19 15 y] and [19 –– 20y]20y]

Thank youThank you

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The Decline of Hepatitis B Virus Infection in the Kingdom ... · PDF fileThe Decline of Hepatitis B Virus Infection in the Kingdom of Saudi Arabia. ... Epidemiology of HBV in Saudi