Epidemiology and Prevention of Epidemiology and Prevention of Hepatitis AHepatitis A in Koreain Korea

Associate ProfessorAssociate ProfessorDepartment of Pediatrics, College of Medicine, Department of Pediatrics, College of Medicine, The Catholic University of KoreaThe Catholic University of Korea

DirectorDirectorDivision of Enteric and Hepatitis Viruses, NIH,Division of Enteric and Hepatitis Viruses, NIH,Korea Centers for Disease Control and PreventionKorea Centers for Disease Control and Prevention

JongJong--Hyun Kim, M.D.Hyun Kim, M.D.

ContentsContents

Etiology of Acute Viral HepatitisEtiology of Acute Viral Hepatitis

Change of Hepatitis A EpidemiologyChange of Hepatitis A EpidemiologySeroprevalenceSeroprevalence of antiof anti--HAVHAVAge distribution of acute hepatitis A patientsAge distribution of acute hepatitis A patients

Status of current hepatitis A vaccineStatus of current hepatitis A vaccine

About South KoreaAbout South Korea

S. Korea

N. Korea

Population: about 48 million, Capital: SeoulPopulation: about 48 million, Capital: SeoulGross domestic Gross domestic products(GDPproducts(GDP): $ 791 billion (12): $ 791 billion (12thth))Gross national Gross national income(GNIincome(GNI): $ 765 billion (11st)): $ 765 billion (11st)Personal GNI: $ 18,372 (41Personal GNI: $ 18,372 (41--4949thth))

Etiology of Acute Viral HepatitisEtiology of Acute Viral Hepatitis

HEV, 1.6

HCV4%

HBV45%

HAV49%

AsanAsan Medical Center, University of Medical Center, University of UlsanUlsan, Seoul, SeoulStudy periods: 2002Study periods: 2002--20042004FulminantFulminant hepatitis: 10 cases (all: hepatitis B)hepatitis: 10 cases (all: hepatitis B)

(n=92)(n=84)

(n=7)

(n=3)%

Song MH. et al. Korean J Med 2005;68:256Song MH. et al. Korean J Med 2005;68:256--6060

HBsAgHBsAg+ rate+ rate1970s: 71970s: 7--8%8%2005: 3.5%2005: 3.5%

school age: <1%school age: <1%

AntiAnti--HCV rate: <HCV rate: <1%1%

Change of Hepatitis A EpidemiologyChange of Hepatitis A Epidemiology

Due to the absence of reporting system in the past, it Due to the absence of reporting system in the past, it was impossible to determine the exact disease was impossible to determine the exact disease burden of hepatitis A. burden of hepatitis A. In the 70s, the prevalence of hepatitis A was so high In the 70s, the prevalence of hepatitis A was so high that, hepatitis A accounted for approximately 2that, hepatitis A accounted for approximately 2--5% of 5% of all hospitalized children in South Korea. This situation all hospitalized children in South Korea. This situation remained the same until the midremained the same until the mid--80s. 80s. Thereafter, the cases had significantly decreased until Thereafter, the cases had significantly decreased until an outbreak had occurred in a city in 1996. Since then, an outbreak had occurred in a city in 1996. Since then, the number of hepatitis A cases gradually increased the number of hepatitis A cases gradually increased and in 2006, 1,923 cases were officially reported. and in 2006, 1,923 cases were officially reported.

Proportion of InProportion of In--patient with Hepatitis A in patient with Hepatitis A in 1970s1970s

Year No of HepA Total No of In-Pt % Year No of HepA Total No

of In-Pt %

1968 31 931 3.3 1973 26 1,010 2.6

1969 15 1,084 1.4 1974 24 844 2.9

1970 16 937 1.7 1975 35 895 3.9

1971 18 922 2.0 1976 20 847 2.4

1972 29 963 3.0 1977 27 1,036 2.6

Total 241 9,469 2.5

St. Mary’s Hospital, The Catholic University of Korea

* HepA, hepatitis A; Pt, patient Lee et al. J Kor Pediatr Soc 1979;22:47-55

Other reports from 1970s: 1.3 Other reports from 1970s: 1.3 -- 6.4%6.4%Choi et al. J Kor Pediatr Soc 1972;15:753 Park et al. J Kor Pediatr Soc 1975;19:180Shim et al. J Kor Pediatr Soc 1978;21:215 Lee et al. J Kor Pediatr Soc 1978;21:376

First Outbreak of First Outbreak of HepHep A at A at DaejeonDaejeon City in 1990sCity in 1990s

PeriodsPeriods: : July to Dec, 1996July to Dec, 1996InstitutionInstitution: St. Mary: St. Mary’’s Hospital, The Catholic s Hospital, The Catholic

University of Korea University of Korea Total number of patients:Total number of patients: 60 cases (31 children, 60 cases (31 children,

30 adults)30 adults)Age distributionsAge distributions: age 4 : age 4 –– 26 years26 years

Children: 3 cases in 4Children: 3 cases in 4--5 year of age, 13 cases in 65 year of age, 13 cases in 6--10 10 year of age, 15 cases in 11year of age, 15 cases in 11--15 year of age15 year of age

adults: 29 cases in 16adults: 29 cases in 16--26 year of age26 year of age

Choi

et al. J Kor

Pediatr

Infect Dis

1997;4:90-6

Prevalence of Hepatitis A on 1988Prevalence of Hepatitis A on 1988--9898

0 0 1 12

1 12 3

5

28

0

5

10

15

20

25

30

1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

No.

of

ca

se

s

M : F = 1.2 : 1.0

Kim et al. J Kor

Pediatr

Infect Dis

1998;5:230-8

Four hospitals attached to The Catholic University of Korea

Age Distribution of Hepatitis A on 1988Age Distribution of Hepatitis A on 1988--9898

4

2

19 19

12

7

12

0

5

10

15

20

≤ 5 6-10 11-15 16-20 21-25 26-30 31-35 35-40

No.

of

case

s

Age of distribution (yrs)

Four hospitals attached to The Catholic University of Korea

Kim et al. J Kor

Pediatr

Infect Dis

1998;5:230-8

Reported Cases of Hepatitis A in National Sentinel Reported Cases of Hepatitis A in National Sentinel Surveillance System (Korea CDC)Surveillance System (Korea CDC)

Age (yr) 2006 2005 2004 2003 2002 2001

0-4 4 8 2 3 2 15-9 20 13 8 2 6 3

10-14 63 33 15 12 12 515-19 105 58 28 35 47 620-29 914 370 182 166 147 4830-39 659 241 100 80 77 2440-49 116 60 15 8 21 1050-59 16 5 4 3 1 3> 60 26 8 5 3 4 5Total 1923 796 359 312 317 105

Hepatitis A Cases on 2006Hepatitis A Cases on 2006

Seoul793 cases

Incheon121 cases

Kyonggi768 cases

Pusan< 10 cases

Daegu10 cases21

86

39

<10 <10

12

<1020

2006’Total cases: 1,923

Seoul to Pusan (400km)by car: 5 hrsby high speed train

: 3 hrs

1st city: Seoul2nd city: Pusan3rd city: Daegu

Why so different?

Outbreak of Hepatitis A in Outbreak of Hepatitis A in KongjuKongju City City (June, 2004)(June, 2004)

Confirmed acute hepatitis A patients = 54 casesConfirmed acute hepatitis A patients = 54 cases< 9 yrs, 2; 10< 9 yrs, 2; 10--19 yrs, 12; 2019 yrs, 12; 20--29 yrs, 31; 3029 yrs, 31; 30--39 yrs, 6; > 40yrs, 339 yrs, 6; > 40yrs, 3

Epidemiological survey was performed.Epidemiological survey was performed.

ThirtyThirty--nine out of 54 patients: visiting history of a restaurant nine out of 54 patients: visiting history of a restaurant with family or friends from late April to midwith family or friends from late April to mid--May. May.

That restaurant used the underground water kept in waterThat restaurant used the underground water kept in water--tank to clean tableware.tank to clean tableware.

Most recent Most recent serosero--prevalacneprevalacne Study IStudy I

Study period: 2006Study period: 2006’’Enrolled institutes: 5 university hospital Enrolled institutes: 5 university hospital Regions: Seoul (2), Regions: Seoul (2), IncheonIncheon (1), (1), SuwonSuwon (1), (1), DaeguDaegu (1)(1)

Seoul

Suwon

Daegu

Incheon

Seoul, Suwon, Incheon regions are relatively endemic area in Korea

Most recent Most recent serosero--prevalacneprevalacne Study IIStudy II

Sample Sizes: total 1,000 Sample Sizes: total 1,000 (equally divided by each (equally divided by each institute)institute)1-4 year: 100 cases (every age interval)5-9 year: 125 cases (every age interval)10s: 250 cases (every age interval)20s, 30s: 150 cases each (2 year interval)40s: 100 cases (2 year interval)50s’, > 60s’: 50 cases each

Test: Test: ElecsysElecsys AntiAnti--HAV reagent kit (Roche)HAV reagent kit (Roche)Electrochemiluminescence Immunoassay (ECLIA)Positive: Immunity by past infection or vaccination

Result: Result: AgeAge--specific specific SeroSero--prevalence of Hepatitis A prevalence of Hepatitis A Antibody in Korea Antibody in Korea

38

6835

5633

64

4848

2020

4 84

32

8 4 84

16

3

17

4

2728

43

70

8380

9084

10010010096

0

10

20

30

40

50

60

70

80

90

100

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20-2122-2324-2526-2728-2930-3132-3334-3536-3738-3940-4142-4344-4546-4748-4950-5960-69

Anti-HAV+(%)

(yr)

Result: Result: SeroSero--prevalence of Hepatitis A Antibody prevalence of Hepatitis A Antibody by Age Groupsby Age Groups

56 57

13.68

15.8

73.2

96 100 100

0102030405060708090

100

1-4 5-9

10-14

15-19

20-29

30-39

40-49

50-59

61-69Anti-HAV+(%)

(yr)

Result: Result: SeroSero--prevalence of Hepatitis A Antibody prevalence of Hepatitis A Antibody by Regionsby Regions

0102030405060708090

100

1- 4

5- 9

10- 1415- 1920- 2930- 3940- 4950- 5960- 69

Seoul Incheon Suwon Daegu*

*

Seoul, Suwon, Incheon regions are relatively endemic area in Korea

Changes of antiChanges of anti--HAV HAV IgGIgG in Koreain Korea

0

20

40

60

80

100

1979-81 1989 1997 2006

1-56-1011-1516-2021-3031-4041-50

(%)

Age group

Korean J Int Med 1982;25:19-26Korean J Int Med 1992;43:57-63 J Kor Pediatr Soc 1997’ Symposium Abs Book p96

10s-20s

Hepatitis A Vaccine in South KoreaHepatitis A Vaccine in South Korea

First launch of a hepatitis A vaccine in the late First launch of a hepatitis A vaccine in the late 19971997

Now, KFDA has Now, KFDA has licencedlicenced four different four different HepAHepAvaccinesvaccines

Havrix (GSK)Vaqta (MSD)Epaxal (Berna Biotech)Avaxim (Sanofi-Pastuer)

Recommend vaccination at above 12 months of Recommend vaccination at above 12 months of age with interval over 6 months (not universal)age with interval over 6 months (not universal)

Incidence of Hepatitis A among Korean SoldiersIncidence of Hepatitis A among Korean Soldiers

7.4

1.6

4.4

9.8

6.2

0123456789

10

2000 2001 2002 2003 2004

/ 100,000 persons

No. of reported cases 37 8 22 49 31No. of Outbreak 2 1 1 5 2No. of epidemic cases 23 3 3 31 4

Kang CI, et al. J Korean Med Sci 2007;22:546

Total No. of Korean Soldiers ≈

500,000Range of Ages: 19 - 27

AgeAge--specific specific SeroprevalenceSeroprevalence of Antiof Anti--HAV Antibody inHAV Antibody in Korean Patients with Chronic Liver Diseases Korean Patients with Chronic Liver Diseases (2005)(2005)

0 023

64

8594

100 100 98

0

20

40

60

80

100

<20

21-2526-3031-3536-4041-4546-5051-55>56

Age distribution: >40, 79%; 31-39, 15%Cause of CLD: HBV 65%, alcohol 17.7%, HCV 12.9%

Ewha University HospitalSong HJ, et al. J Korean Med Sci 2007;22:218

Coverage Rate of Hepatitis A VaccinesCoverage Rate of Hepatitis A Vaccines

0.E+00

1.E+05

2.E+05

3.E+05

4.E+05

5.E+05

6.E+05

7.E+05

8.E+05

9.E+05

1.E+06

1998

1999

2000

2001

2002

2003

2004

2005

2006

Birth No Doses1997 675,2271998 640,126 103,4551999 616,322 182,4632000 636,780 296,5082001 557,228 365,6022002 494,625 498,8822003 493,471 562,1862004 476,052 591,5052005 438,062 744,9952006 942,061

sum of total doses 4,184,202 / sum of total birth No. 5,027,893 during 1998-2006 = 41.6% (estimation)

Actual coverage rate of Hepatitis A vaccine in 1-2 year old on 2006: 40%(Kim KH et al. unpublished data)(Kim KH et al. unpublished data)

Catch-up campaign to pre-

or school children

SummarySummary

For those aged less than 10 years old, antiFor those aged less than 10 years old, anti--HAV HAV prevalence was above 50%, mainly contributed to prevalence was above 50%, mainly contributed to the result of vaccination.the result of vaccination.

However, the prevalence of antibody in the 10s However, the prevalence of antibody in the 10s and 20s were 10and 20s were 10--30%, a number significantly 30%, a number significantly lower than other age groups.lower than other age groups.

Almost all people above 40 years old have Almost all people above 40 years old have antibody to HAV.antibody to HAV.

DISCUSSIONDISCUSSION

According to Regions, there is a According to Regions, there is a difference of prevalence of acute hepatitis difference of prevalence of acute hepatitis A in small country. A in small country. →→ why? why?

10s having lowest anti10s having lowest anti--HAV among 10s, HAV among 10s, 20s and 30s 20s and 30s →→ lowest reported cases?lowest reported cases?