Review
Copyright ©2007 Baishideng Publishing Group Co.
World J Gastroenterol. Mar 28, 2007; 13(12): 1770-1787
Published online Mar 28, 2007. doi: 10.3748/wjg.v13.i12.1770
Table 1 Association of HLA alleles with Chronic HBV infection across global population
HLAEffectCountry and casesHealthy controlsRecoveredChronic infectionReference
HLAI
HLA A*0206VPTaiwan (Taiwanese borigines)34229138[4]
HLA B-35VPTaiwan (Han Chinese)9832498[4]
HLA A*2VP/Disease severityJapan[8]
HLA B18, B35, B40, Cw3Susceptibility to chronic HBV infectionRussia[5]
HLA A3, B18Susceptibility to chronic HBV infectionKazakh[5]
HLA: B8-Cw7 haplotypeLiver cancer associated with HBV infectionSenegal9698[6]
HLA B*8VPUSA (Caucasians)342194[7]
HLA A*01-B*08-DRB1*03, B*44-Cw*1601 and B*44-Cw*0501 haplotypeVPUSA (Caucasians)342194[7]
HLA II
HLA DRB1*1202#VPTaiwan (Han Chinese)9832498[4]
HLA DQA1*0302VPChina148 (R), 212 (AC)207[113]
HLA DRB1*0301, DQA1*0501, DQB1*0301VPChina1063054[10]
HLA DR9, DQ9VPChina5630[11]
HLA-DRB1*06, DRB1*08, and DRB1*16VPChina20072[14]
HLA DR9VPKorea (ESRD patients)94624383[19]
HLA DRB1*11# and DRB1*15VPIndia10026[12]
HLA DQA1 *0501, DQB1 *0301VPUSA (African American)6031[18]
HLA DR3Susceptibility to HBV infection & vertical transmissionChina (Pregnant women)4078[15]
HLA-DRB1*1201/1202#Susceptibility to liver cirrhosisChina (Cirrhosis subjects from Hubei area)108116[13]
HLA B13, B8, DR7, DR13, DQ3Susceptibility to chronic HBV infectionTurkey5050[9]
HLA DQA1 0501, DQB1 0301, DRB1 1102# haplotypeVPUSA (African American)6031[18]
Table 2 Association of HLA allele with protection from chronic HBV infection across global population
HLAEffectCountry and casesNCRCIReference
HLAIHLA B61Early HBeAg seroconversionTaiwan (chronically infected children)81[114]
HLA A*26No disease progression in HBV carriersJapan[8]
HLA A-24 and Cw1Low risk for HBV related chronic diseaseTurkey5050[9]
HLA A2VCRussia[5]
HLA A11VCKazakh[5]
HLA A*0301VCUSA (Caucasians)342194[7]
HLA II
HLA DRB1*4001VCTaiwan (Taiwanese Aborigines)9832498[4]
HLA DRB1*0406, DRB1*0701VCTaiwan (Han Chinese)9832498[4]
HLA DQA1*0301, DQA1*0102VC/ACChina148 (R) & 212 (AC)207[113]
HLA DRB1*1101/ *1104, DQA1*0301VCChina1063054[10]
HLA DR12 (DRB1*1201)VCChina5630[11]
HLA-DRB1*07VC/Protection from HBV infection.China20072[14]
HLA DR6 (DRB1*13)VCKorea (ESRD patients)94624383[19]
HLA DRB1*13VCIndia10026[12]
HLA DRB1*1301 and DRB1*1302VCGambia (children & Adult men)891 & 25218 & 195185 & 40[110]
HLA DRB1*1301/1302VCSpain241138[115]
HLA DRB1*1301/1302VCGermany101117[116]
HLA DR13 (DRB1*13)VCGermany2083332[117]
HLA DQB1*0503Early HBeAg seroconversionTaiwan (Chronically infected children)81[114]
HLA DR13Resistance to HBV infection & vertical transmissionChina (Pregnant women)4078[15]
HLA-DRB1*1501/1502Protection from liver cirrhosisChina (Cirrhosis subjects from Hubei area)108116[13]
HLA DR5No disease progression in HBV carriersJapan[8]
Table 3 HLA allele association with Non-responsiveness to HBsAg vaccine across global population
HLAEffectCountryVaccineesRsNRsReference
HLAIHLA B54Non- responsivenessChinaHealthy vaccinees3029[118]
HLA A*0602, A*1101 and B*35Non-responsiveness/ antibody productionJapanHealthy medical students[35]
HLA A1, A10, B15, B40.Non responsivenessIndiaHealthy volunteers15 of 87 Rs15[37]
HLA A10, CW4Non-responsivenessTurkeyHealth care workers12[119]
HLA A1, B8Non-responsivenessGermany, PolandESRD Patients on hemodialysis11934[44,46]
HLA B8Non-responsivenessBelgiumHomosexual vaccinees399[120]
HLA A2Non-responsivenessSpainHemodialysis patients[121]
HLA II HLA DR7##Non- responsivenessChinaHealthy vaccinees3029[118]
HLA DRB1*07##Non-responsivenessChina (Han)Healthy vaccinees145118[122]
HLA DR14, DR52Non- responsivenessChinese (Taiwan)Non responder vaccinees26[123]
HLA DRB1*0405, DRB1*1101, DR4Non-responsiveness/ antibody productionJapanHealthy medical students[35]
HLA DQ2$Non responsivenessIndiaHealthy volunteers15 of 8715[37]
HLA DR7#Non-responsivenessTurkeyHealth care workers12[119]
HLA DR3, DQ2$Non-responsivenessGermany, PolandESRD Patients on hemodialysis11934[44,46]
HLA DR3Non-responsivenessBelgiumHomosexual vaccinees399[120]
HLA DRB1*07#, *DQB1*02$, and DPB1*1101Non-responsivenessBelgiumVaccinees134117[39]
HLA DRB1*03, DRB1*14Non-responsivenessFranceHemodialysis patients301114[124]
HLA DRB1*1302, DQB1*0604, DQA1*0102Non-responsivenessSwedenHealthy vaccinees6953[48]
HLA DRB1*0701#, DQB1*0202$Non-responsivenessUKVaccinees11786[125]
HLA DRB1*0701#, DQB1*0202$Non-responsivenessUKHBsAg Non responders[45]
HLA DQB1*02$Non-responsivenessItalyNeonates7649LR, 43SR 19TNR[34]
HLA DRB1*1601, DQB1*0502, DQA1*0102 HaplotypeNon-responsivenessSloveniaHealth care workers6036[126]
HLA DR3, DR7#, DQ2$Non-responsivenessSpainHemodialysis patients[121]
HLA DRB1*3, DRB1*7, DRB1*14xNon-responsivenessGermanyHealthy adults & Infant vaccinees53 & 5673 & 62[127]
HLA-B8, SC01, DR3 and HLA B44-FC31, DR7#Non-responsivenessUSAHealthcare worker20[33,49]
HLA DRB1*07#Non-responsivenessUSAHealthy vaccinees8579[128]
HLA III HLA C4A*6, C4A*Q0##, Bf*F, Bf*S07Non-responsivenessGermany, PolandESRD Patients on hemodialysis11934[46]
HLA C4AQ0##Non-responsivenessItalyNeonates4026LR, 21SR, 10TNR[41]
HLA C4AQ0##Non-responsivenessItalyNeonates7649LR, 43SR 19TNR[34]
HLA C4AQ0##Non-responsivenessGermanyHealthy vaccinees5373[42]
Table 4 HLA association with responsiveness to HBsAg vaccine across global population
HLAEffectCountryVaccineesRsNRsReference
HLAI, HLA A1, B7, B12Responsiveness (Low)Germany PolandESRD Patients on hemodialysis11934[46]
HLA A1, A19, B5, B27, Cw2, Cw4Responsiveness (High)Germany PolandESRD Patients on hemodialysis11934[46]
HLA II, HLA DRB1*02ResponsiveChina (Han)Healthy vaccinees145118[122]
HLA DRB1*0101, DRB1*08032, DQA1, DQB1, DPA1 and DPB1ResponsivenessJapanHealthy medical students[35]
HLA DR4Responsiveness (Low)Germany, PolandESRD Patients on hemodialysis11934[46]
HLA DRB1*010, DR5, DPB1*040, DQB1*0301, DQB1*0501.ResponsivenessBelgiumVaccinees134117[39]
HLA DRB1*01, *DRB1*15# and DRB1*16ResponsivenessFranceHemodialysis patients301114[124]
HLA DRB1*1301, *DR15#, DQA1*0103, DQA1*0102, DQB1*0603,ResponsivenessSwedenHealthy vaccinees6953[48]
HLA DRB1*11, DQB1*0301ResponsivenessItalyNeonates7649LR, 43SR 19TNR[34]
HLA DRB1*1 DRB1*13, *DRB1*15#ResponsivenessGermanyHealthy adults & infant vaccinees109135[127]
HLA III C4A*6, C4B*2, Bf*FResponsiveness (High)Germany PolandESRD Patients on hemodialysis11934[46]
Table 5 Association of HLA haplotypes with response to HbsAg vaccination across global population
HAPLOTYPEEffectCountryVaccineesRsNRsReferences
HLA DR4, 1122 (DRB1*0401-22, 1122)- DR53 (DRB4*0101101, 0102/3)-DQB4 (DQB1*04)Non-responsivenessChina[129]
HLA DR14-DR52Non-responsivenessChinese (Taiwan)Non-responder vaccinees33[123]
HLA A1, B8, Bfs, C4AQ0, C4B1, DR3, DQ2 and HLA A1, B8, BfF, C4A6, C4B2, DR3, DQ2Non-responsivenessGermany, PolandESRD Patients on hemodialysis34119[46]
HLA DRB4*0101-DRB1*0301/DRB3* *0101 DQB1*0202 and DPB1*0201 DRB1*0701/DRB4*0101, DQB1*020*Non-responsivenessBelgiumVaccinees134117[39]
HLA DQB1*0604, DQA1*0102, DRB1*1302 haplotypeNon-responsivenessSwedenHealthy vaccinees6953[48]
HLA C4A*Q0, DRB1*0301, DQB1*02Non-responsivenessItalyNeonates4026LR, 21SR 10TNR[41]
HLA C4AQ0, DQB1*02Non-responsivenessItalyNeonates7649LR, 43SR 19TNR[34]
HLA B44-DRB1*0701-DQB1*0202Non-responsivenessUKVaccinees11786[125]
HLA DRB1*1601, DQB1*0502, DQA1*0102 haplotypeNon-responsivenessSloveniaHealth care workers6036[126]
HLA B8-DR3Non-responsivenessGermanyHealthy adult & infant vaccinees109135[127]
HLA DQB1*0603, DQA1*0102, DR15 and HLA DQB1*0603, DQA1*0103, DRB1*1301 haplotypeResponsivenessSwedenHealthy vaccinees6953[48]
HLA DRB1*11, DQB1*0301ResponsivenessItalyNeonates7649LR, 43SR 19TNR[34]
Table 6 Association of HLA alleles with susceptibility to viral persistence &chronic HCV infection across global population
HLAEffectCountryNCRChronicinfection
Reference
ACCLD/CHC
HLAIHLA-B61, Cw3,VP/HCV infectionJapan29360[69]
HLA B54VP with CLDJapan9163397[68]
HLA B55, -B56, B70VPJapan172113[59]
HLA A3, B-35, B-46VPKorea206137[109]
HLA A28, A29, B14HCV infectionEgypt[55]
HLA A-19HCV infectionSaudi people.122146[54]
HLA-A10, HLA-B35, HLA-B40 and HLA-Cw3VP-CLDRussia[5]
HLA-A30, B35, B41, Cw2, A1-B35, A9-B8VP-CLD-LCRussia107[57]
HLA B8, B18VP-CHCIreland86141[60]
HLA C*04VPIreland (Whites)86139[56]
HLA B14VP & active hepatitis CItaly489117[130]
HLA B18Susceptibility to CLDSpain1164893[131]
HLA-A*2301 and HLA-Cw*04VPUSA231444[58]
HLA-Cw*07,Risk factor for vertical infectionItaly (infants born to HCV+ mothers)44 uninfected infants born to HCV+ mothers21[16]
HLA II HLA DR4, DQB1*0401 DQB1*0402VP/ HCV infectionJapan29360[69]
HLA DRB1*0405, DQB1*0401VP with CLDJapan9163397[68]
HLA DRB1*0405, DQB1*0401VP with LCJapan12165067[70]
HLA DQB1*0503VP with LCJapan2014360[132]
HLA DRB1*0301#, DQB1*0201, DQB1*0502VP/CHCThailand140432136[133]
HLA, DRB1*0803, DQB1*0601 and DQB1*0604VPKorea206137[109]
HLA DRB1*0301#VPEgypt (Hemophilic and HCV-, HCC+ patients)15 Healthy & 25 HCV-10 HCV+15 (HCV- HCC+)[134]
HLA DR7HCV infectionEgypt[55]
HLA-DRB1*0701, DRB1*15, DRB4*0101Viral persistenceUK (European)85170[135]
HLA DQB1*0201VP-CHCIreland86141[60]
HLA DRB1*0701 (HCV 1b)VPIreland (females receiving HCV 1b contaminated AntiD immunoglobulin)8472[136]
HLA DRB1*1001, DRB1*1101VP/CLDItaly1794199[137]
HLA DQB1*0502VP-CLDItaly2003542107[138]
HLA DR14, DR17VP-CLDItaly703439[139]
HLA DRB1*0301VP-CHCGermany101105[140]
HLA DRB1*07VP-CLDGerman & North Europeans204599[94]
HLA DR B1*13 and DRB1*14Susceptibility to infectionGerman & North Europeans204599[94]
HLA DR3#Susceptibility to chronic diseaseSpain1164893[131]
HLA DRB1*13 and DRB1*07Necro inflammatory activity during infectionPoland134[95]
HLA DRB1*13 alleleVPPoland134[95]
DRB1*03# and DQB1*0201(male gender)CLD/LCFrance233[141]
HLA G*010401, -DRB1*0701, -DRB1*1401 and homozygosity for HLA-G 14bp deletionRisk factor for vertical infectionItaly(infants born to HCV+ mothers)44 uninfected infants born to HCV+ mothers21[16]
HLA DRB*4001High viral loadTaiwan[142]
HLA III MICA-A4Susceptibility to CLDSpain1164893[131]
Table 7 Association of HLA alleles with Protection from HCV infection and viral clearance
HLA IEffectCountryNCRChronic infection
Reference
ACCHC/CLD
HLAIHLA-B51, -B52, B61, -Cw1, Cw3, and Cw4VCJapan172113[59]
HLA A2ACJapan172113[59]
B50 (21)VCEgypt[55]
HLA-B8,Protection from infectionSaudi people122146[54]
HLA-Cw4Protection from chronic infectionRussia[5]
HLA A*03,B*07,B*27,Cw*01VC/Protection from chronic infectionIreland86141[60]
HLA-A*1101,HLA-B*57 and HLA-Cw*0102Viral clearanceUSA231444[58]
HLA-Cw*0602Protection against vertical infectionItaly (infants born to HCV+ ve mothers)44 uninfected infants born to HCV+ mothers21[16]
HLA Bw4180/KIR3DS1HCV carriersSpain1165147 (LC), 54 (HCC)[64]
HLA-C1/KIR2DL3VC/protection from infectionUK352685[62]
HLA A*34,B*56Low viral loadTaiwan[142]
HLA II HLA-DR9- DQB1*0301 and DQB1*0303VC/protection from HCV infectionJapan29360[69]
HLA DRB1*1302, DRB1*1101## and DQB1*0604 allelesAC/no CLDJapan9163397[68]
HLA DRB1*12(1201/1202), DQBI*0301, DRB3*03AC/no CLDJapan2014360[132]
HLA DRB1*0901,DQB1*0303AC-no LCJapan12165067[70]
HLA DRB1*04, DRB1*0701, DQA1*0201,DQB1*0301VCThailand140432136[133]
HLA DRB1*0301, DQA1*0501 and DQB1*0201VC/protection from HCV infectionKorea206137[109]
HLA DRB1*0101##VCEgypt (Hemophilic and HCV- HCC+ ve patients)15 Healthy & 25 HCV-10 HCV+15 HCV- HCC+[134]
HLA DRI and DR3VC/Protection from infectionSaudi people122146[54]
HLA DRB1*11#VC/Protection from infectionTurkey4349[143]
HLA DQA1*03 and DQB1*0302VC/Protection from chronic infectionN.European whites177104[144]
HLA-DRB1*0301,DRB1*1101#, DRB1*1201# and HLA-DQB1*0301Viral clearanceUK (European)85170[135]
HLA DRB1*04, DQA1*03 and DQB1*0301VC/Protection from chronic infectionUK1344955[145]
HLA DQB1*0302Protection from infectionUK1344955[145]
HLA DRB1*01##. (HCV 1b)VCIreland (females who received HCV 1b contaminated AntiD immunoglobulin)8472[136]
HLA DRB1*0101##, DRB1*0401, DRB1*15VC/Protection from chronic infectionIreland86141[60]
HLA DRB1*0101##Viral clearanceIreland7384[78, 146]
HLA DR5#Protection from chronic hepatitis CItaly489117[130]
HLA II HLA DRB1*1601, DQB1*0502Protection from HCV infectionSardinia (Thalassemia major for transfusion)606 healthy & 30 HCV- patients116[147]
HLA DRB1*1104, and DRB3*03Protection from chronic manifestation /carriesItaly1794199[137]
HLA DRB1*1104,DQB1*0301VCItaly2003542107[138]
HLA DR 11VC/Protection from infectionItaly703429[139]
HLA DQB1*0301Protection from HCV related HCCItaly14429[148]
HLA DRB1*1301 and DQA1*0103Protection from chronic HCV infectionGermany101105[140]
HLA-DRB1*15011Viral clearance/ ProtectionGermany2149[149]
HLA-DRB1*11(DR5) and HLA-DQB1*03(DQ3)Protection from CLDGermany501108[150]
HLA-DR11AC/Protection from CLDSpain1164893[131]
HLA DQB1*0301Protection from chronic infectionPoland103129[108]
HLA DRB1*11Mild liver damagePoland134[95]
HLA DQB1*0301 and DRB1*1101VCFrance80025103[74]
HLA DQB1*0301 and female sexVCFrance80063282[75]
HLA DRB1*11Protection from progression of liver diseaseFrance233[141]
HLA DRB1*11 (female association)AC/less severity of chronic hepatitisFrance83233[76]
HLA DQB1*0301VC (strongly in Black subjects)USA200374[77]
HLA DRB1*0101, DQB1*0501VC (in white subjects)USA200374[77]
HLA DR13Protection against vertical infectionItaly (infants born to HCV+ ve mothers)17 (serum reverted)18[17]
HLA-DQB1*06, -G*0105N, DRB1*1104 and -DRB1*1302 allelesProtection against vertical infectionItaly (infants born to HCV+ ve mothers)44 uninfected infants born to HCV+ mothers21[16]
HLA DRB1*1502Low viral loadTaiwan[142]
Table 8 HLA Haplotype association with HCV viral clearance and persistence across global population
HLAEffectCountryNCRChronic infection
Reference
ACCLC/CHC
Viral persistence
HLA Cw3- DR4-DQB1*0401 or *0402, and HLA-B61-DR4 -DQB1*0401 or 0402VP/chronic infectionJapan29360[69]
HLA B54-DRB1*0405-DQB1*0401 haplotypeVP-CLDJapan9163397[68]
HLA DRB1*0405-DQB1*0401 haplotypeVP with LCJapan12165067[70]
HLA DRB1*0301, DQA1*0501, DQB1*0201VPThailand140432136[133]
A*01-B*08-Cw*07-DRB1*03011-DQB1*0201VP-CHCIreland86141[60]
HLA DRB1*15-DQB1*0602High viral load/increased risk for disease severityIreland (viremic females)57[71]
HLA A*11, C*04VPIreland (Whites)86139[56]
HLA DQA1*0201-DQB1*0201Susceptibility to Chronic hepatitis CItaly1794199[151]
HLA DR3/MICA-A4/B18Susceptibility to chronic diseaseSpain1164893[131]
HLA DRB1*0701-DQA1*0201-DQB1*02 and DRB1*1501-DQA1*01-DQB1*0602VP-CLDPoland103129[108]
HLA DRB1*0301 -DQB1*0201VPUSA[77]
HLA-Cw*04-B*53VPUSA231444[58]
Viral clearance
HLA B44-DRB1*1302-DQB1*0604 and DRB1*1302-DQB1*0604AC/no progression to CLDJapan9163397[68]
HLA DRB1*0901-DQB1*0303AC-no LCJapan12165067[70]
HLA A*03-B*07-DRB1*15-DQB1*0602 and A*02-B*27-Cw*01-DRB1*0101-DQB1*0501VC/Protection from chronic infectionIreland86141[60]
DRB1*0701 and DQB1*02Stable viral load/slow disease progressionIreland (viremic females)57[71]
HLA DRB1*1104, DQA1*0501, DQB1*0301 haplotypeProtection from Chronic hepatitisItaly1794199[151]
HLA DRB1*1104, DQB1*0301VCItaly2003542107[138]
HLA DRB1*0101 -DQB1*0501 haplotypeViral clearance (in white subjects)USA200374[77]
Table 9 HLA association with response to interferon therapy in chronic hepatitis (B and C) patients across global population
HLAEffectCountryRNRReferences
Hepatitis B
HLA DQA1*0501 and DQB1*0301ResponsivenessChina3228[85]
HLA-DRB1*14ResponsivenessChina1124[14]
HLA DRB1*04,DQA1*0303Non-responsivenessChina3228[85]
HLA-DRB1*07 (HBV type c)Non-responsivenessChina7[152]
HLA-DQB1*07Low responseChina1124[14]
Hepatitis C
Non responsiveness
HLAIHLA B54Non responsivenessJapan2047[86]
HLAII, HLA DR9Non responsivenessJapan[153]
HLA DR6Non responsivenessJapan2132[154]
HLA DRB1*04 (males and HCV1b)Non responsivenessChina1011[84]
HLA B1*13Non responsivenessTurkey[155]
DRB1*07Non responsivenessFrance50120[75]
Responsiveness
HLAIHLA B55, B62 and Cw3ResponsivenessJapan54118[156]
HLA B51, CW1ResponsivenessJapan[153]
HLA B44Responsiveness to Interfron + RibavirinSpain5352[87]
HLAII HLA DRB*10101ResponsivenessJapan32106[157]
HLA DR6ResponsivenessJapan2132[154]
HLA DRB1*07 (females and HCV 2b)ResponsivenessChina1011[84]
HLA DR2ResponsivenessEgypt2530[158]
DQB1*06(HCV genotype 1)ResponsivenessFrance50120[75]
HLA DRB1*0404ResponsivenessCanada664[88]
Haplotypes
HLA A-24-B54-DR4Non responsivenessJapan2047[86]
HLA B7-DRB10101ResponsivenessJapan32106[157]
DRB1*0701-DQA1*0201-DQB1*02ResponsivenessPoland2926[108]