22 A
(GOT/GPT
~1900 Catarrhal Jaundice 1912 Cockayne Infectious hepatitis 1946 MacCallum Infectious hepatitis A and B 1965 Blumberg Discovery of hepatitis B virus 1973 Feinstone Discovery of hepatitis A virus 1974 Prince Non-A, non-b hepatitis 1983 Balayan Discovery of hepatitis E virus 1989 Houghton Isolation of hepatitis C virus cdna
EM no no no yes yes Vaccine no yes yes yes no Chronic infection fecal-oral percutaneous permucosal percutaneous permucosal percutaneous permucosal fecal-oral Route of transmission feces blood/bloodproducts blood/bloodproducts blood/bloodproducts feces Source of virus HEV Hepeviridae RNA HDV Deltaviridae RNA HCV Flaviviridae RNA HBV Hepadnaviridae DNA HAV Picornaviridae RNA Virus
(80-95%) 10% 76-97%) 38 40-70%) * 0.01% (USA) (50 1.8% 0.3%)
EVENTS IN HEPATITIS A VIRUS INFECTION Clinical illness Infection ALT Response Viremia HAV in stool IgM IgG 0 1 2 3 4 5 6 Week 7 8 9 10 11 12 13
GEOGRAPHIC DISTRIBUTION OF HEPATITIS A VIRUS INFECTION
case / 100,000 10 9 8 7 6 5 4 3 2 1 0 1987 1991 1995 1999 2003 Year
500 600 300 400 200 100 0
(2000-2008 ) 600 500 400 300 200 100 0 2000 2001 2002 2003 2004 2005 2006 2007 2008
2006 1-2 10 IA HAV) 2006 4-5 IA HAV) 12 2006 7-9 15 IA HAV) 1A
100 80 60 40 20 1973 1984 1994 2003 0 0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65
(2006-8 ) 165 50
(2006-8 )
Case Numbers of AVH in Korea Data from CDC, Korea 6 th Korea-Japan Liver Symposium July 19 2009, Kyongju 2009 25 155 CDC
2010 A
2010 A
HAV PCR-primers Capsid Noncapsid 1 735 7415 7478 5 AAAn 449 557 2799 3296 482 509 HAV+482-P-FAM PCR 1st PCR primers(498bp) 2907 3172 Nested PCR primers(280bp)
3A 16 cases (28%) from 10 pref. Similar to recent Korean Isolates 1A (2010 type) 31 cases (53%) from 17 pref. Similar to Philippines Isolates 26 from 13 pref. had 100% identity 1A (2006 type) 9 cases (15%) from 7 pref. Similar to 2006 Japansese Isolates 1A (others):2, 1B:1 N=59
Comparison of HAV (3A) sequences between Japanese and Korean isolates 100608-Kb1 100602-Kg2 [AJ299464]NOR-21/Norway_3A HAV_OsakaC_S10-116 HAVSeoul298 HAVSeoul398 HAVSeoul1 100521-Mi2 HAV_22-035 HAV_22-041 HAVSeoul416 [EU011791]PN-IND/India_3A IND-HAV-97F_3A [AB279734]HAJ95-8/Japan_3A [AB279733]HA-JNG08-92/Japan_3A [AB258387]HA-JNG06-90F/Japan_3 [AB279735]HAJ85-1/Japan_3B [AB300205]KRM238G59/Japan_3B [AB425339]KRM003G72/Japan_3B [X83302]FG/Italy_1A [X75215]GBM/WT/Germany_1A [K02990]LA/USA_1A [EU131373]HAV5/Uruguay_1A [AB020569]FH3/Japan_1A 100427-Kb2_58-7436_ 100603-Ng2_A-E_ [AF485328]LY6/China_1A DL3_1A [AB020564]AH1/Japan_1A [AF357222]LU38/China_1A [M14707]HM-175/Australia_1B [AF268396]HAF-203/Brazil_1B HM175_1B [AF314208]L-A-1/China_1B [M20273]MBB/Germany_1B M20273-MBB_1B [AY644670]SLF88/USA_2B CF53/Berne_2A 0.02
A P1-2A 2BC P3 structural proteins non-structural proteins VPg (3B) 5 NTR (IRES) VP4 2A VP2 VP3 VP1 2B 2C 3A 3B 3C 3D 3 NTR AAAAAA VP2 VP3 VP1 2A VP4 VP2 VP3 VP1 2A RNA replicase VP4 capsid
Genealogical tree of HAV strains Strain KRM031 CR326 HM175 TKM005 CF53 SLF88 PA21 KRM003 CY145 AGM27 JM55 IA IB VII VI IIIA IIIB V II IV 100 90 80 70 Nucleotide sequence homology (%) based on 168 nt at VP1/2A cording region
HAV PCR-primers Capsid Noncapsid 1 735 7415 7478 5 AAAn 449 557 2799 3296 482 509 HAV+482-P-FAM PCR 1st PCR primers(498bp) 2907 3172 Nested PCR primers(280bp)
HAV 100% inhibition HAV HAV HAV HAV HAV 0% inhibition HAV HAV HAV HAV - % inhibition x 100 -
HAV HAV IgM
Aimmugen *Havrix Vaqta Avaxim Epaxal Al(OH) 3 Al(OH) 3 Al(OH) 3 (Virosome) 2-PE 2-PE KRM003 HM175 CR326F GBM RG-SB IIIB IB IA IA IB *: (Twinrix)
(Dose) 140000 120000 100000 80000 60000 40000 20000 0 95 96 97 98 99 00 01 02 03 04 (year) 12 84 28 2 3