Original Article
Association between an MHC Class II Allele and Clearance of Hepatitis B Virus in the Gambia
N Engl J Med 1995; 332:1065-1069April 20, 1995
- Abstract
Background
The course of hepatitis B virus (HBV) infection does not appear to be determined by variations in viral virulence and may be influenced by the host immune response. We studied the distribution of human leukocyte antigens in children and adult men in the Gambia who spontaneously recovered from HBV infection as compared with the distribution of these antigens in subjects with persistent infection.
Methods
In a two-stage, case –control study, we analyzed the frequency of MHC class I antigens and class II haplotypes in subjects with either transient or persistent HBV infection. MHC class I typing was performed by microlymphocytotoxicity assays. MHC class II typing was performed with analysis of restriction-fragment–length polymorphisms (RFLPs), supplemented by other techniques.
Results
In the first stage (the study of children up to the age of 10 years), the RFLP pattern 25-1, which includes the class II allele HLA-DRB1*1302, was found in 58 of 218 subjects with transient HBV infection (26.6 percent) and 30 of 185 subjects with persistent infection (16.2 percent) (relative risk of carrying the 25-1 pattern in the persistently infected group as compared with the transiently infected group, 0.53; 95 percent confidence interval, 0.32 to 0.90; P = 0.012). In the second stage (the study of adults), HLA-DRB1*1302 was found in 50 of 195 subjects with transient HBV infection (25.6 percent) and in 3 of 40 subjects with persistent infection (7.5 percent) (relative risk, 0.24; 95 percent confidence interval, 0.04 to 0.80; P = 0.012). The RFLP pattern 13-2, which includes the class II allele DRB1*1301, was less frequent in children with persistent infection than in those with transient infection, an association that was neither confirmed nor excluded by the data on adults. Possible associations with HLA class I antigens found in children were not supported by the data on adults.
Conclusions
The MHC class II allele DRB1*1302 was associated with protection against persistent HBV infection among both children and adults in the Gambia.
Media in This Article
Figure 1
Increase in the Prevalence of Antibody against the HBV Core Antigen and Changes in the Carriage of Hepatitis B Surface Antigen with Age in the Gambia.Table 1
Frequencies of MHC Class I Antigens in Children and Adults with Persistent or Transient HBV Infection.Article Activity
- Article
Infection with the hepatitis B virus (HBV) may result in a number of conditions ranging from asymptomatic persistent carriage to fulminant hepatitis with liver failure. Most infected people have acute hepatitis during which the virus is eliminated. About 80 percent of adults in West Africa have been infected with HBV, and in about 15 percent of these persons the virus is not cleared.1 Persistent HBV infection predisposes patients to chronic liver disease and hepatocellular carcinoma2; HBV-related hepatocellular carcinoma is the leading cause of death among men of working age in the Gambia.3,4
The outcome of HBV infection does not appear to be determined by variations in virulence among viral strains. Instead, the course of the disease may be influenced by the host immune response. Although a small proportion of people with persistent infection have specific types of immunodeficiency, such as human immunodeficiency virus (HIV) infection5 or agammaglobulinemia,6 the majority are not immunocompromised. In West Africa, children under the age of 10 years acquire HBV infection asymptomatically from older siblings or playmates, although the mechanism of transmission is unclear.7,8 Mother-to-child transmission such as that seen in the Far East is rare. An immature immune system, as seen in newborns, and the tolerance-producing effects of the transplacental transfer of HBV e antigen are unlikely to affect the outcome of infection.
Variations in immune response are often associated with polymorphism of the major histocompatibility complex (MHC). The role of the MHC phenotype in the outcome of HBV infection has been examined, but no firm conclusion has been reached.9-13 Many studies have been only large enough (with 33 to 79 subjects positive for hepatitis B surface antigen) to detect very strong associations between the MHC phenotype and the disease state. Most of these studies have used serologic methods of MHC class II typing. Such methods diminish sensitivity, because they assign a large number of alleles to the same serologic specificity.
We compared the distribution of HLA antigens in children and adults in the Gambia who spontaneously recovered from HBV infection with the distribution of antigens in those with persistent infection.
Methods
Study Subjects
The study subjects were all West Africans living in the western, coastal region of the Gambia in the area surrounding the capital, Banjul. Two different groups were recruited between 1988 and 1990 for two stages of the study. In the first stage, children up to 10 years of age were recruited at the Royal Victoria Hospital, Banjul, and the Medical Research Council (MRC) Hospital, Fajara, where they had been seen for a variety of conditions unrelated to HBV. In the second stage, adult men were recruited from among healthy blood donors. Both groups had previously been studied as part of a case–control study of susceptibility to malaria.14 Permission for the study was granted by the Joint Ethics Committee, and the study was approved by the Scientific Coordinating Committee. Consent for phlebotomy was obtained from each child's parent or guardian.
In both stages, the subjects were grouped according to the results of serologic tests for HBV. People who had never been exposed to HBV were negative for antibodies against the HBV core antigen (hereafter referred to as HBV core antibody). People who had spontaneously recovered from HBV infection were positive for IgG HBV core antibody and negative for HBV surface antigen. People with persistent HBV infection were positive for both HBV core antibody and hepatitis B surface antigen. People with recent HBV infection who may not have had sufficient opportunity to eliminate hepatitis B surface antigen (i.e., those who were positive for that antigen and for IgM HBV core antibody) were excluded from the analysis. One hundred seven people who had been vaccinated against HBV were classified as unexposed and were not included in the analysis of HLA frequencies. Five people with HIV antibodies were excluded from the analysis.
Serologic Testing
Plasma samples were obtained from all subjects and stored at -20°C. Their serologic status with regard to HBV core antibody, IgM HBV core antibody, and hepatitis B surface antigen and the concentrations of antibody to hepatitis B surface antigen were determined by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions (Boehringer–Mannheim, Munich, Germany). HIV-antibody status was determined by ELISA (Wellcozyme, Wellcome, Beckenham, United Kingdom), with positive tests confirmed by the Western blot assay.
MHC Typing
Class I serotyping was performed on lymphocytes, which were available from about half the subjects in each group. Serologic MHC class I types were determined by standard microlymphocytotoxicity assays of fresh or cryopreserved cells, using 180 well-characterized types of antiserum.14 MHC class II typing was performed by analysis of restriction-fragment–length polymorphisms (RFLPs) as described elsewhere, with the restriction enzymes TaqI and BamHI.14,15 In this assay, band patterns determined by Southern blot analysis correspond to MHC class II haplotypes and are expressed as two numbers separated by a hyphen (e.g., 13-2, 25-1). This analysis was supplemented, when necessary, by amplification by the polymerase chain reaction and blotting with sequence-specific oligonucleotides.14,15 All subjects were assigned an MHC class II type.
Statistical Analysis
The frequencies of MHC class I phenotypes and of RFLP-defined class II haplotypes were compared between people who had recovered from HBV infection and those with persistent infection with regard to 23 MHC class I antigens and 10 class II haplotypes by the chi-square test. When multiple comparisons are made concurrently, apparently significant associations may arise by chance. To avoid such errors, we first made multiple comparisons in the first group (children), and then tested them in the second group (adults) with a restricted hypothesis generated during the first stage of study.16 Relative risks, calculated from the crude odds ratios and given with 95 percent confidence intervals, reflect the likelihood of carrying a specific MHC type in the persistently infected group as compared with the transiently infected group. The ethnic composition of the Gambia is mixed, containing Mandinka (42 percent), Jola (14 percent), Wolof (14 percent), and Fula (12 percent), as well as several less common groups.15 Therefore, Mantel–Haenszel tests were performed to assess a possible confounding effect of ethnic origin. Among the adults, concentrations of antibody to hepatitis B surface antigen were compared between subjects with HLA-DRB1*1302 and those without that allele, by the unpaired t-test.
Results
Of the 1344 children recruited, 891 were unexposed and 453 (33.7 percent) were positive for HBV core antibody. Of these, 185 (40.8 percent) were positive for hepatitis B surface antigen and negative for IgM HBV core antibody (i.e., they had persistent infection), and 218 (48.1 percent) were positive for IgG HBV core antibody, negative for IgM HBV core antibody, and negative for hepatitis B surface antigen (i.e., they had transient infection). The remaining 50 children (11.0 percent) were excluded from the study because they were positive for both hepatitis B surface antigen and IgM HBV core antibody (i.e., they had recent infection). The increase in the carriage of HBV core antibody and hepatitis B surface antigen with age is shown in Figure 1Figure 1
Increase in the Prevalence of Antibody against the HBV Core Antigen and Changes in the Carriage of Hepatitis B Surface Antigen with Age in the Gambia.. Of the 260 adults, 25 were unexposed and 235 (90.4 percent) were positive for HBV core antibody. Of these, 40 (17.0 percent) had persistent infection, and 195 (82.9 percent) had transient infection. The frequencies of MHC class I antigens and class II haplotypes in the children are shown in Table 1Table 1Frequencies of MHC Class I Antigens in Children and Adults with Persistent or Transient HBV Infection. and Table 2Table 2
Frequencies of RFLP-Defined Class II Haplotypes in Children with Persistent or Transient HBV Infection., respectively, and those in the adults are shown in Table 1 and Table 3Table 3
Frequencies of RFLP-Defined Class II Haplotypes in Adults with Persistent or Transient HBV Infection..Possible associations between the MHC class I antigens HLA-B50 (relative risk, undefinable; 95 percent confidence interval, 1.2 to ∞; P = 0.015) and HLA-Cw1 (relative risk, 9.82; 95 percent confidence interval, 1.2 to infinity; P = 0.02) and persistent carriage of hepatitis B surface antigen were suggested by the data from the study of children (Table 1). These associations, however, were not supported by the data from the study of adults (Table 1). Although none of the class I phenotypes studied were associated with clearance of HBV, the power of this study to detect class I associations was lower than the power to detect class II associations, because only about half the subjects underwent MHC class I typing, and class I antigens are more diverse than class II antigens in this population.
MHC class II haplotypes were initially determined with the restriction enzyme TaqI.15 The RFLP pattern 25-1, which corresponds to the class II haplotypes DRB1*1302–DRB3*0301–DQA1*0102–DQB1*0501 (DRw13/DQw5) and DRB1*1302–DRB3*0301–DQA1*0102–DQB1*0604 (DRw13/DQw6), was found in 58 of the 218 children with transient HBV infection (26.6 percent) and in 30 of the 185 children with persistent infection (16.2 percent) (relative risk, 0.53; 95 percent confidence interval, 0.32 to 0.90; P = 0.012) (Table 2). This pattern was associated with a protective effect against persistent carriage of HBV. The RFLP pattern 13-2, which corresponds to the class II haplotype DRB1*1301–DRB3*0101–DQA1*0103–DQB1*0603, was also reduced in frequency in persistently infected children (relative risk, 0.35; 95 percent confidence interval, 0.1 to 1.0; P = 0.037). No other haplotype studied showed a significant alteration in frequency.
We then analyzed these two possible associations in the adult group. HLA-DRB1*1302 was found in 50 of 195 adults with transient HBV infection (25.6 percent) and 3 of 40 adults with persistent infection (7.5 percent) (relative risk, 0.24; 95 percent confidence interval, 0.04 to 0.80; P = 0.012) (Table 3). After stratification according to ethnic group, the Mantel–Haenszel weighted relative risk was 0.23 (95 percent confidence interval, 0.05 to 0.83; P = 0.022), and the possibility of a significant confounding effect of ethnic origin was thereby excluded. The possible association with HLA-DRB1*1301 was neither confirmed nor excluded by the data on adults. HLA-DRB1*1301 was present in 1 of 40 adults with persistent infection and in 7 of 195 adults with transient infection (odds ratio, 0.69; 95 percent confidence interval, 0.02 to 5.62; P = 1.0).
Children and adults with the RFLP pattern 25-1 were further subdivided according to whether they had the DQw5 or the DQw6 allele. Relative risks and 95 percent confidence intervals were calculated for the two haplotypes (Table 4Table 4
Differential Analysis of the Relative Risk Associated with Individual DRB11302 Haplotypes.), and the elimination of HBV was found to be associated with both. This indicates that protection from persistent carriage of HBV was primarily associated with HLA-DR rather than with the HLA-DQ molecules encoded by the RFLP 25-1 pattern, a localization that is important in analyzing the molecular basis of this finding.A possible confounding effect of variation in the closely linked TNFα gene promoter was analyzed. Among these subjects, HLA-DRB1*1302 and a TNFα promoter variant are in linkage disequilibrium.17 Stratified analyses indicated that the effect of HLA-DR was independent of the TNFα gene polymorphism (data not shown). In 25 adults with DRB1*1302 (mean age, 28.6 years), the mean (±SD) concentration of antibody to hepatitis B surface antigen was 15.5±41.5 IU per liter. In 25 adults without DRB1*1302 (mean age, 32.2 years), the mean concentration of antibody to hepatitis B surface antigen was 22.3±48.5 (P = 0.598).
Discussion
We found an association between the RFLP-defined MHC class II haplotype 25-1 and clearance of HBV infection among groups of children and adults in the Gambia. The 25-1 pattern represents two MHC class II haplotypes, DRB1*1302–DRB3*0301–DQA1* 0102–DQB1*0501 and DRB1*1302–DRB3*0301–DQA1*0102–DQB1*0604. Further analysis showed that both DRB1*1302 haplotypes were associated with the clearance of HBV; it is therefore probable that one or both of the shared HLA-DR alleles are responsible for this association. HLA-DRB1*1302 is found only on the 25-1 RFLP pattern, whereas HLA-DRB3*0301 is also found on other RFLP-defined haplotypes in the Gambia.15 Furthermore, the product of DRB1*1302 is expressed at a higher level than the product of DRB3 and may thus be of greater functional importance, particularly because T cells restricted by products of the DRB1 locus are identified more frequently than are DRB3-restricted T cells with regard to most antigens.
The RFLP pattern 13-2, which corresponds to the class II haplotype DRB1*1301–DRB3*0101–DQA1*0103–DQB1*0603, may also be associated with resistance to persistent HBV infection, as suggested by the data on persistently infected children. Interestingly, the DRB1 allele of this haplotype, DRB1*1301, differs from HLA-DRB1*1302 by the substitution of a single amino acid, a change of glycine (*1302) to valine (*1301) at position 86 of the DRβ chain. Combining the data on adults and children with RFLP pattern 13-2 gives a relative risk for persistent infection of 0.46 (95 percent confidence interval, 0.15 to 1.20; P = 0.09). Our data are therefore consistent with the hypothesis that both DRB1*1302 and DRB1*1301 protect against persistent HBV infection.
It is possible that RFLP pattern 25-1 is a marker for a linked non–HLA-DR gene variant that confers protection against persistent HBV infection. We believe that this is unlikely. On one side of HLA-DR lies the TNFα promoter polymorphism, which is in strong linkage disequilibrium with DRB1*1302 in this population but is not associated with protection from persistent HBV infection. On the other side of HLA-DR, the HLA-DQ variants that were analyzed also showed no association. Therefore, on RFLP pattern 25-1, HLA-DRB1*1302 seems most likely to be associated with protection against persistent HBV infection.
HLA-DRB1*1302 is also associated with a reduced risk of severe malaria in Gambian children. This finding may help to explain the high frequency of the DRB1*1302–DRB3*0301–DQA1*0102–DQB1*0501 and DRB1*1302DRB3*0301DQA1*0102DQB1*0604 haplotypes in this population.11 Malaria and HBV are both important causes of premature death in West Africa. Severe malaria has a high death rate in children under the age of five years. Deaths from HBV infection usually occur in adults. It is therefore possible that there is a selection advantage for the DRB1*1302 allele in the Gambia associated with both HBV and malaria.
Some children in West Africa carry hepatitis B surface antigen for several years before HBV is eliminated completely, and they may therefore have been misclassified as long-term carriers. This phenomenon may account for the lower relative risk of carrying the 25-1 haplotype in adult men with persistent HBV carriage as compared with children.
DRw6 — the serologic supertype of DRB1*1302 and DRB1*1301 — was identified in two previous studies as potentially protective against persistent HBV infection. Van Hattum et al. found DRw6 nearly twice as often in North European patients in whom HBV had cleared than in those who had not eliminated the virus.9 In a study of factors influencing the response of chronic HBV infection to interferon therapy, we found that DRw6 was associated with a favorable response.18 HLA-DRB1*1302 has been found in 10 to 26 percent of Africans and African Americans, 4 to 11 percent of whites, and 0 to 25 percent of Asians in large population surveys.19 The association we have identified may be relevant to other groups of people.
The activity of HBV-specific CD4+ T-helper cells is markedly reduced in patients with persistent infection as compared with patients who have acute, self-limiting infection.20 The responses of T-helper cells increase during acute exacerbations of chronic HBV infection, particularly at the time of seroconversion from hepatitis B e antigen to antibody to hepatitis B e antigen.21 Through its role in antigen presentation, the class II molecule is critical to the development of T-helper–cell responses. The variable ability of class II molecules to present antigens may appear as variability in the response of T-helper cells. In patients with persistent HBV infection, failure to develop antibodies to hepatitis B e antigen and surface antigen, and to develop sufficient numbers of active HBV-specific cytotoxic T lymphocytes, may be related at least in part to the lack of T-helper–cell response mediated by class II molecules with relatively poor antigen-presenting ability. The finding of equivalent levels of antibodies to the hepatitis B surface antigen in people with and without DRB1*1302 suggests that the mechanism of the MHC association is not mediated through the humoral response to this antigen.
A protective effect against cervical carcinoma related to the human papillomavirus has been reported that is associated with DRB1*1302 and DRB1*1301. 22 HBV, Plasmodium falciparum, and the human papillomavirus are complex microorganisms with many potential T-cell epitopes that have different MHC restriction elements. The MHC associations in these diseases suggest that only a small number of immune responses may be of particular importance for protection.
Recent advances in the study of peptides bound to MHC class I and II molecules and the identification of sequence motifs in bound peptides23,24 have facilitated the analysis of the molecular basis of associations between MHC types and disease. Using this approach, termed “reverse immunogenetics,” we have identified a possible basis for the association of an MHC class I allele, HLA-B53, with resistance to malaria in the Gambia.25 Analysis of the association of HLA-DRB1*1302 with the clearance of HBV will be facilitated by the relatively small size of the HBV genome and the availability of its complete sequence. Recently, through the analysis of individual peptides eluted from both HLA-DRB1*1302 and HLA-DRB1*1301, we have identified related peptide-binding motifs for these alleles (unpublished data), allowing us to predict possible epitopes for these class II molecules.
Our findings implicate variation in the genes governing the immune response of the host as one factor that can explain the variable outcome of hepatitis B infection and offer an approach to elucidating the molecular mechanisms of viral clearance. Further analysis of this association may help identify strategies for the prevention and management of chronic HBV infection.
Supported by Boehringer–Mannheim, the Wellcome Trust, and the Medical Research Council, United Kingdom, and by a grant from Applied Immune Sciences, Inc. (to Dr. Thursz). Dr. Hill is a Wellcome Trust Senior Clinical Fellow. Dr. Kwiatkowski is a Senior Clinical Fellow of the Medical Research Council.
We are indebted to Hilton Whittle for reviewing the data and making valuable comments on the manuscript, to Estee Torok for assistance with the serologic assays, and to N. Anstey, P. Twumasi, D. Brewster, A. Hughes, L. Bayo, and L. Manneh for participating in the collection of samples.
Source Information
From the Hepatology Unit, Academic Department of Medicine, St. Mary's Hospital Medical School, Imperial College, London (M.R.T., H.C.T.); the Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (D.K., C.E.M.A., A.V.S.H.); and the Medical Research Council Laboratories, Fajara, the Gambia (B.M.G., A.V.S.H.).
Address reprint requests to Dr. Thursz at the Department of Medicine, St. Mary's Hospital Medical School, London W2 1NY, United Kingdom.
- References
References
1
Ryder RW ,Whittle HC ,Wojiecowsky T , et al. Screening for hepatitis B virus markers is not justified in West African transfusion centres. Lancet 1984;2:449-452
CrossRef | Web of Science | Medline2
Beasley RP ,Hwang LY ,Lin CC ,Chien CS . Hepatocellular carcinoma and hepatitis B virus: a prospective study of 22 707 men in Taiwan. Lancet 1981;2:1129-1133
CrossRef | Web of Science | Medline3
Ryder RW ,Whittle HC ,Sanneh AB ,Ajdukiewicz AB ,Tulloch S ,Yvonnet B . Persistent hepatitis B virus infection and hepatoma in The Gambia, west Africa: a case-control study of 140 adults and their 603 family contacts. Am J Epidemiol 1992;136:1122-1131
Web of Science | Medline4
Kiire CF . Hepatitis B infection in sub-Saharan Africa: the African Regional Study Group. Vaccine 1990;8:Suppl:S107-S112
CrossRef | Web of Science | Medline5
Krogsgaard K ,Lindhardt BO ,Nielsen JO , et al. The influence of HTLV-III infection on the natural history of hepatitis B virus infection in male homosexual HBsAg carriers. Hepatology 1987;7:37-41
CrossRef | Web of Science | Medline6
Hermaszewski RA ,Webster AD . Primary hypogammaglobulinaemia: a survey of clinical manifestations and complications. Q J Med 1993;86:31-42
Web of Science | Medline7
Marinier E ,Barrois V ,Larouze B , et al. Lack of perinatal transmission of hepatitis B virus infection in Senegal, West Africa. J Pediatr 1985;106:843-849
CrossRef | Web of Science | Medline8
Botha JF ,Ritchie MJ ,Dusheiko GM ,Mouton HW ,Kew MC . Hepatitis B virus carrier state in black children in Ovamboland: role of perinatal and horizontal infection. Lancet 1984;1:1210-1212
CrossRef | Web of Science | Medline9
van Hattum J ,Schreuder GM ,Schalm SW . HLA antigens in patients with various courses after hepatitis B virus infection. Hepatology 1987;7:11-14
CrossRef | Web of Science | Medline10
Forzani B ,Actis GC ,Verme G , et al. HLA-DR antigens in HBsAg-positive chronic active liver disease with and without associated delta infection. Hepatology 1984;4:1107-1110
CrossRef | Web of Science | Medline11
Lepage V ,Degos F ,Carella G ,De Lima M ,Giraud MC ,Degos L . HLA-Cw7 and HBsAg negative chronic active hepatitis. Tissue Antigens 1981;18:105-107
CrossRef | Web of Science | Medline12
Kaslow RA ,Shaw S . The role of histocompatibility antigens (HLA) in infection. Epidemiol Rev 1981;3:90-114
Web of Science | Medline13
Almarri A ,Batchelor JR . HLA and hepatitis B infection. Lancet 1994;344:128-129
CrossRef | Web of Science14
Hill AVS ,Allsopp CE ,Kwiatkowski D , et al. Common west African HLA antigens are associated with protection from severe malaria. Nature 1991;352:595-600
CrossRef | Web of Science | Medline15
Hill AVS ,Allsopp CE ,Kwiatkowski D , et al. Extensive genetic diversity in the HLA class II region of Africans, with a focally predominant allele, DRB1*1304. Proc Natl Acad Sci U S A 1992;89:2277-2281
CrossRef | Web of Science | Medline16
Hill AVS . HLA and infection. J R Coll Physicians Lond 1992;26:11-16
Medline17
McGuire W ,Hill AVS ,Allsopp CEM ,Greenwood BM ,Kwiatkowski D . Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature 1994;371:508-510
CrossRef | Web of Science | Medline18
Scully L ,Brown D ,Lloyd C ,Shein R ,Thomas HC . Immunological studies before and during interferon therapy in chronic HBV infection: identification of factors predicting response. Hepatology 1990;12:1111-1117
CrossRef | Web of Science | Medline19
Tsuji K, Aizawa M, Sasazuki T, eds. HLA 1991: proceedings of the eleventh annual international histocompatibility workshop and conference held in Yokohama, Japan, 6–13 November, 1991. Oxford, England: Oxford University Press, 1992.
20
Ferrari C ,Penna A ,Bertoletti A , et al. Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. J Immunol 1990;145:3442-3449
Web of Science | Medline21
Tsai SL ,Chen PJ ,Lai MY , et al. Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens: implications for hepatitis B e antigen seroconversion. J Clin Invest 1992;89:87-96
CrossRef | Web of Science | Medline22
Apple RJ ,Erlich HA ,Klitz W ,Manos MM ,Becker TM ,Wheeler CM . HLA DR-DQ associations with cervical carcinoma show papillomavirus-type specificity. Nat Genet 1994;6:157-162
CrossRef | Web of Science | Medline23
Falk K ,Rotzschke O ,Stevanovic S ,Jung G ,Rammensee HG . Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 1991;351:290-296
CrossRef | Web of Science | Medline24
Chicz RM ,Urban RG ,Gorga JC ,Vignali DA ,Lane WS ,Strominger JL . Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp Med 1993;178:27-47
CrossRef | Web of Science | Medline25
Hill AVS ,Elvin J ,Willis AC , et al. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 1992;360:434-439
CrossRef | Web of Science | Medline
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Frank Grünhage, Jacob Nattermann. (2010) Viral hepatitis: Human genes that limit infection. Best Practice & Research Clinical Gastroenterology 24:5, 709-723
CrossRef20
Yong Kwang Park, Jung Min Lee, Do Young Kim, Hye Young Chang, Ja Kyung Kim, Chun Kyon Lee, Jun Yong Park, Sang Hoon Ahn, Kwan Sik Lee, Kwang Hyub Han. (2010) Association Between Polymorphism of Tumor Necrosis Factor-α Promoter and Response to Lamivudine Treatment in Patients with Chronic Hepatitis B. Digestive Diseases and Sciences 55:7, 2043-2048
CrossRef21
Ding-Qiang Chen, Yong Zeng, Jie Zhou, Ling Yang, Shibo Jiang, Jian-Dong Huang, Liwei Lu, Bo-Jian Zheng. (2010) Association of candidate susceptible loci with chronic infection with hepatitis B virus in a Chinese population. Journal of Medical Virology 82:3, 371-378
CrossRef22
Wei Sun, Fan Zhong, Lianteng Zhi, Gangqiao Zhou, Fuchu He. (2009) Systematic -omics analysis of HBV-associated liver diseases. Cancer Letters 286:1, 89-95
CrossRef23
T. L. Lenz, C. Eizaguirre, J. P. Scharsack, M. Kalbe, M. Milinski. (2009) Disentangling the role of MHC-dependent âgood genes' and âcompatible genes' in mate-choice decisions of three-spined sticklebacks Gasterosteus aculeatus under semi-natural conditions. Journal of Fish Biology 75:8, 2122-2142
CrossRef24
Jessica A. Howell, Kumar Visvanathan, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein. (2009) A novel role for human leukocyte antigen-DP in chronic hepatitis B infection: A genomewide association study. Hepatology 50:2, 647-649
CrossRef25
Naoto Keicho, Satoru Itoyama, Koichi Kashiwase, Nguyen Chi Phi, Hoang Thuy Long, Le Dang Ha, Vo Van Ban, Bach Khanh Hoa, Nguyen Thi Le Hang, Minako Hijikata, Shinsaku Sakurada, Masahiro Satake, Katsushi Tokunaga, Takehiko Sasazuki, Tran Quy. (2009) Association of human leukocyte antigen class II alleles with severe acute respiratory syndrome in the Vietnamese population. Human Immunology 70:7, 527-531
CrossRef26
Song Chen, Wenli Zhao, Wenting Tan, Baoyan Xu, Yunjie Dan, Qing Mao, Xuemei Kuang, Yuming Wang, Guohong Deng. (2009) Association of TBX21 T-1993C polymorphism with viral persistence but not disease progression in hepatitis B virus carriers. Hepatology Research 39:7, 716-723
CrossRef27
Yoichiro Kamatani, Sukanya Wattanapokayakit, Hidenori Ochi, Takahisa Kawaguchi, Atsushi Takahashi, Naoya Hosono, Michiaki Kubo, Tatsuhiko Tsunoda, Naoyuki Kamatani, Hiromitsu Kumada, Aekkachai Puseenam, Thanyachai Sura, Yataro Daigo, Kazuaki Chayama, Wasun Chantratita, Yusuke Nakamura, Koichi Matsuda. (2009) A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nature Genetics 41:5, 591-595
CrossRef28
Emeli Lundström, Henrik Källberg, Marina Smolnikova, Bo Ding, Johan Rönnelid, Lars Alfredsson, Lars Klareskog, Leonid Padyukov. (2009) Opposing effects of HLA-DRB1*13 alleles on the risk of developing anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis. Arthritis & Rheumatism 60:4, 924-930
CrossRef29
Yi-Wen Huang, Chung-Yi Hu, Chi-Lin Chen, Ya-Tang Liao, Chun-Jen Liu, Ming-Yang Lai, Pei-Jer Chen, Sien-Sing Yang, Jui-Ting Hu, Ding-Shinn Chen, Jia-Horng Kao. (2009) Human leukocyte antigen-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus. Journal of Medical Virology 81:4, 588-593
CrossRef30
Pietro Invernizzi, Carlo Selmi, Francesca Poli, Sara Frison, Annarosa Floreani, Domenico Alvaro, Piero Almasio, Floriano Rosina, Marco Marzioni, Luca Fabris, Luigi Muratori, Lihong Qi, Michael F. Seldin, M. Eric Gershwin, Mauro Podda, . (2008) Human leukocyte antigen polymorphisms in italian primary biliary cirrhosis: A multicenter study of 664 patients and 1992 healthy controls. Hepatology 48:6, 1906-1912
CrossRef31
C. TOLLENAERE, J. BRYJA, M. GALAN, P. CADET, J. DETER, Y. CHAVAL, K. BERTHIER, A. RIBAS SALVADOR, L. VOUTILAINEN, J. LAAKKONEN, H. HENTTONEN, J.-F. COSSON, N. CHARBONNEL. (2008) Multiple parasites mediate balancing selection at two MHC class II genes in the fossorial water vole: insights from multivariate analyses and population genetics. Journal of Evolutionary Biology 21:5, 1307-1320
CrossRef32
Giorgio Sirugo, Branwen J. Hennig, Adebowale A. Adeyemo, Alice Matimba, Melanie J. Newport, Muntaser E. Ibrahim, Kelli K. Ryckman, Alessandra Tacconelli, Renato Mariani-Costantini, Giuseppe Novelli, Himla Soodyall, Charles N. Rotimi, Raj S. Ramesar, Sarah A. Tishkoff, Scott M. Williams. (2008) Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics. Human Genetics 123:6, 557-598
CrossRef33
Edward J. Collins, David S. Riddle. (2008) TCR-MHC docking orientation: natural selection, or thymic selection?. Immunologic Research 41:3, 267-294
CrossRef34
Jean-Pierre Bronowicki, Idrissia Abdelmouttaleb, Laurent Peyrin-Biroulet, Véronique Venard, Hacène Khiri, Nicodème Chabi, Emile K. Amouzou, Hélène Barraud, Philippe Halfon, Ambaliou Sanni, Marc-André Bigard, Alain Le Faou, Jean-Louis Guéant. (2008) Methylenetetrahydrofolate reductase 677 T allele protects against persistent HBV infection in West Africa. Journal of Hepatology 48:4, 532-539
CrossRef35
Arash Mahboubi, Tahereh Hallaj Shooshtari, Mohammad Reza Fazeli, Rasoul Dinarvand, Nasrin Samadi, Mohammad Sharifzadeh, Houshmand Ilka, Saeed Azadi, Mahboubeh Valadkhani. (2008) Comparison of Immunogenicity in Balb/C Mice of Commercially Available Recombinant Hepatitis B Vaccines in Iran. Journal of Medical Sciences(Faisalabad) 8:4, 415-419
CrossRef36
Guohong Deng, Gangqiao Zhou, Rong Zhang, Yun Zhai, Wenli Zhao, Zehui Yan, Chunqing Deng, Xiaoyan Yuan, Baoyan Xu, Xiaojia Dong, Xiumei Zhang, Xuqing Zhang, Zhijian Yao, Yan Shen, Boqing Qiang, Yuming Wang, Fuchu He. (2008) Regulatory Polymorphisms in the Promoter of CXCL10 Gene and Disease Progression in Male Hepatitis B Virus Carriers. Gastroenterology 134:3, 716-726.e2
CrossRef37
X.Q. Zhang, X.J. Hong, X.J. Bai. (2008) Susceptibility to active decompensated cirrhosis is associated with polymorphisms of intercellular adhesion molecule-1 (ICAM-1) in chronic HBV carriers. Journal of Viral Hepatitis 15:3, 173-178
CrossRef38
Jae Youn Cheong, Sung Won Cho, Jung A Lee, Kwang Jae Lee, Hee Jung Wang, Jong Eun Lee, Jin Hong Kim. (2008) Matrix Metalloproteinase-3 Genotypes Influence Recovery from Hepatitis B Virus Infection. Journal of Korean Medical Science 23:1, 61
CrossRef39
Sung Won Cho, Jae Youn Cheong, Young Su Ju, Do Hoon Oh, Young Ju Suh, Kyung Wha Lee. (2008) Human Leukocyte Antigen Class II Association with Spontaneous Recovery from Hepatitis B Virus Infection in Koreans: Analysis at the Haplotype Level. Journal of Korean Medical Science 23:5, 838
CrossRef40
Xuqing Zhang, Xiaojun Hong, Guohong Deng, Xiujuan Bai. (2007) Single nucleotide polymorphisms and functional analysis of class II transactivator (CIITA) promoter IV in persistent HBV infection. Journal of Clinical Virology 40:3, 197-201
CrossRef41
P. Kummee, P. Tangkijvanich, Y. Poovorawan, N. Hirankarn. (2007) Association of HLA-DRB1*13 and TNF-? gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population. Journal of Viral Hepatitis 0:0, 070727121914001-???
CrossRef42
William Abbott, Edward Gane, Ingrid Winship, Stephen Munn, Colin Tukuitonga. (2007) Polymorphism in intron 1 of the interferon-gamma gene influences both serum immunoglobulin E levels and the risk for chronic hepatitis B virus infection in Polynesians. Immunogenetics 59:3, 187-195
CrossRef43
G. Yang, J. Liu, S. Han, H. Xie, R. Du, Y. Yan, D. Xu, D. Fan. (2007) Association between hepatitis B virus infection and HLA-DRB1 genotyping in Shaanxi Han patients in northwestern China. Tissue Antigens 69:2, 170-175
CrossRef44
Jae Youn Cheong, Sung Won Cho, Jeong Young Choi, Jung A Lee, Min Ho Kim, Jong Eun Lee, Ki Baik Hahm, Jin Hong Kim. (2007) RANTES, MCP-1, CCR2, CCR5, CXCR1 and CXCR4 Gene Polymorphisms are not Associated with the Outcome of Hepatitis B Virus Infection: Results from a Large Scale Single Ethnic Population. Journal of Korean Medical Science 22:3, 529
CrossRef45
Hasan Micozkadioglu, Aysegul Zumrutdal, Dilek Torun, Siren Sezer, Fatma Nurhan Ozdemir, Mehmet Haberal. (2007) Low Dose Intradermal Vaccination Is Superior to High Dose Intramuscular Vaccination for Hepatitis B in Unresponsive Hemodialysis Patients. Renal Failure 29:3, 285-288
CrossRef46
Adrian V. S. Hill. (2006) Aspects of Genetic Susceptibility to Human Infectious Diseases. Annual Review of Genetics 40:1, 469-486
CrossRef47
Sang Hoon Ahn, Do Young Kim, Hye Young Chang, Sun Pyo Hong, Jeon-Soo Shin, Yu Seun Kim, Hyejin Kim, Ja Kyung Kim, Yong Han Paik, Kwan Sik Lee, Chae Yoon Chon, Young Myoung Moon, Kwang-Hyub Han. (2006) Association of genetic variations in CCR5 and its ligand, RANTES with clearance of hepatitis B virus in Korea. Journal of Medical Virology 78:12, 1564-1571
CrossRef48
Pei-Jer Chen, Cherry Guan-Ju Lin, Felicia Yi-Fang Lin, Ellson Chen, Lawrence Shih-Hsin Wu. (2006) Genetic structural differences between responders and non-responders to interferon therapy for chronic hepatitis-B patients. Journal of Human Genetics 51:11, 984-991
CrossRef49
Peter T. Donaldson, Anna Baragiotta, Michael A. Heneghan, Annarosa Floreani, Carla Venturi, James A. Underhill, David E.J. Jones, Oliver F.W. James, Margaret F. Bassendine. (2006) HLA class II alleles, genotypes, haplotypes, and amino acids in primary biliary cirrhosis: A large-scale study. Hepatology 44:3, 667-674
CrossRef50
Zane Lombard, Desiré-Lee Dalton, Philip A. Venter, Robert C. Williams, Liza Bornman. (2006) Association of HLA-DR, -DQ, and Vitamin D Receptor Alleles and Haplotypes with Tuberculosis in the Venda of South Africa. Human Immunology 67:8, 643-654
CrossRef51
Jae Youn Cheong, Sung Won Cho, Il Lan Hwang, Seung Kew Yoon, June Hyuk Lee, Choon Sik Park, Jong Eun Lee, Ki Baik Hahm, Jin Hong Kim. (2006) Association between chronic hepatitis B virus infection and interleukin-10, tumor necrosis factor-alpha gene promoter polymorphisms. Journal of Gastroenterology and Hepatology 21:7, 1163-1169
CrossRef52
Yoon Jun Kim, Jung-Hwan Yoon, Chung Yong Kim, Lyoung Hyo Kim, Byung Lae Park, Hyoung Doo Shin, Hyo-Suk Lee. (2006) IGF2 polymorphisms are associated with hepatitis B virus clearance and hepatocellular carcinoma. Biochemical and Biophysical Research Communications 346:1, 38-44
CrossRef53
Li Shu, Neal Touzjian, Deng Nan, Nicholas Kushner, Amie J. Strong, Wei Zeping, Geng Zhaohui, Yichen Lu. (2006) Recombinant hepatitis B large surface antigen, successfully produced in Escherichia coli, stimulates T-cell response in mice. Vaccine 24:20, 4409-4416
CrossRef54
Yasuro Futagawa, Kayo Waki, Junchao Cai. (2006) The association of HLA-DR13 with lower graft survival rates in hepatitis B and primary sclerosing cholangitis caucasian patients receiving a liver transplant. Liver Transplantation 12:4, 600-604
CrossRef55
F. Feo, M.R. De Miglio, M.M. Simile, M.R. Muroni, D.F. Calvisi, M. Frau, R.M. Pascale. (2006) Hepatocellular carcinoma as a complex polygenic disease. Interpretive analysis of recent developments on genetic predisposition. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1765:2, 126-147
CrossRef56
Keyur Patel, Suzanne Norris, Lauralynn Lebeck, Anne Feng, Michael Clare, Stephen Pianko, Bernard Portmann, Lawrence M. Blatt, James Koziol, Andrew Conrad, John G. McHutchison. (2006) HLA class I allelic diversity and progression of fibrosis in patients with chronic hepatitis C. Hepatology 43:2, 241-249
CrossRef57
Z. Lombard, A. E. Brune, E. G. Hoal, C. Babb, P. D. Van Helden, J. T. Epplen, L. Bornman. (2006) HLA class II disease associations in southern Africa. Tissue Antigens 67:2, 97-110
CrossRef58
Angela J. Frodsham. (2005) Host genetics and the outcome of hepatitis B viral infection. Transplant Immunology 14:3-4, 183-186
CrossRef59
Yogita Ghodke, Kalpana Joshi, Arvind Chopra, Bhushan Patwardhan. (2005) HLA and disease. European Journal of Epidemiology 20:6, 475-488
CrossRef60
Andrew Godkin, Miles Davenport, Adrian V.S. Hill. (2005) Molecular analysis of HLA class II associations with hepatitis B virus clearance and vaccine nonresponsiveness. Hepatology 41:6, 1383-1390
CrossRef61
Franck Prugnolle, Andrea Manica, Marie Charpentier, Jean François Guégan, Vanina Guernier, François Balloux. (2005) Pathogen-Driven Selection and Worldwide HLA Class I Diversity. Current Biology 15:11, 1022-1027
CrossRef62
XIMIN LIN, NOAH J ROBINSON, MARK THURSZ, DANIEL M ROSENBERG, ANDREW WEILD, JEANNE M PIMENTA, ANDREW J HALL. (2005) Chronic hepatitis B virus infection in the Asia-Pacific region and Africa: Review of disease progression. Journal of Gastroenterology and Hepatology 20:6, 833-843
CrossRef63
Alicia Habegger de Sorrentino, Roxana López, Patricia Motta, Karina Marinic, Adrián Sorrentino, Ernesto Iliovich, Andrea E. Rubio, Jorge Quarleri, Horacio Salomón. (2005) HLA class II involvement in HIV-associated Toxoplasmic encephalitis development. Clinical Immunology 115:2, 133-137
CrossRef64
Yasunori Ichiki, Xiao-Song He, Shinji Shimoda, Hiromi Ishibashi, Emmet B. Keeffe, Lorenzo Rossaro, M. Eric Gershwin. (2005) T cell immunity in hepatitis B and hepatitis C virus infection: implications for autoimmunity. Autoimmunity Reviews 4:2, 82-95
CrossRef65
Leslie A. Knapp. (2005) The ABCs of MHC. Evolutionary Anthropology: Issues, News, and Reviews 14:1, 28-37
CrossRef66
J. Schad, J. U. Ganzhorn, S. Sommer. (2005) PARASITE BURDEN AND CONSTITUTION OF MAJOR HISTOCOMPATIBILITY COMPLEX IN THE MALAGASY MOUSE LEMUR, MICROCEBUS MURINUS. Evolution 59:2, 439
CrossRef67
Jae Youn Cheong, Sung Won Cho, Sun Kyo Lim, Do Hyun Shin, Seung Kew Yoon, Jong Eun Lee, Ki Baik Hahm, Jin Hong Kim. (2005) Lack of Association between Hepatitis B Virus Infection and Polymorphism of Mannose-Binding Lectin Gene in Korean Population. Journal of Korean Medical Science 20:1, 65
CrossRef68
R. HARF, S. SOMMER. (2005) Association between major histocompatibility complex class II DRB alleles and parasite load in the hairy-footed gerbil, Gerbillurus paeba, in the southern Kalahari. Molecular Ecology 14:1, 85-91
CrossRef69
M. Jazayeri, A. A. Basuni, N. Sran, R. Gish, G. Cooksley, S. Locarnini, W. F. Carman. (2004) HBV core sequence: definition of genotype-specific variability and correlation with geographical origin. Journal of Viral Hepatitis 11:6, 488-501
CrossRef70
K. Mathias Wegner, Martin Kalbe, Helmut Schaschl, Thorsten B.H. Reusch. (2004) Parasites and individual major histocompatibility complex diversity—an optimal choice?. Microbes and Infection 6:12, 1110-1116
CrossRef71
Guohong Deng, Gangqiao Zhou, Yun Zhai, Shuqing Li, Xuhong Li, Ya Li, Ruifang Zhang, Zhijian Yao, Yan Shen, Boqing Qiang, Yuming Wang, Fuchu He. (2004) Association of estrogen receptor ? polymorphisms with susceptibility to chronic hepatitis B virus infection. Hepatology 40:2, 318-326
CrossRef72
Mark Thursz. (2004) Pros and cons of genetic association studies in hepatitis B. Hepatology 40:2, 284-286
CrossRef73
Annapurna Vyakarnam, David Sidebottom, Shahed Murad, James A. Underhill, Philippa J. Easterbrook, Angus G. Dalgleish, Mark Peakman. (2004) Possession of human leucocyte antigen DQ6 alleles and the rate of CD4 T-cell decline in human immunodeficiency virus-1 infection. Immunology 112:1, 136-142
CrossRef74
S. MASCHERETTI, H. HINRICHSEN, S. ROSS, P. BUGGISCH, J. HAMPE, U. R. FOELSCH, S. SCHREIBER. (2004) Genetic variants in the CCR gene cluster and spontaneous viral elimination in hepatitis C-infected patients. Clinical and Experimental Immunology 136:2, 328-333
CrossRef75
P. Aroviita, J. Partanen, P. Sistonen, K. Teramo, R. Kekomaki. (2004) High birth weight is associated with human leukocyte antigen (HLA) DRB1*13 in full-term infants. European Journal of Immunogenetics 31:1, 21-26
CrossRef76
Antoni Gay??, Anna Esteve, Jordi Casabona, Jeanette J McCarthy, Jaume Martorell, Thomas F Schulz, Denise Whitby. (2004) Amino acid residue at position 13 in HLA-DR beta chain plays a critical role in the development of Kaposi's sarcoma in AIDS patients. AIDS 18:2, 199-204
CrossRef77
Ya-Fang Wu, Li-Yu Wang, Tsung-Dao Lee, Hans Hsienhong Lin, Chi-Tan Hu, Mu-Liang Cheng, Shih-Yen Lo. (2004) HLA phenotypes and outcomes of hepatitis B virus infection in Taiwan. Journal of Medical Virology 72:1, 17-25
CrossRef78
Shelley Segal, Adrian V.S Hill. (2003) Genetic susceptibility to infectious disease. Trends in Microbiology 11:9, 445-448
CrossRef79
Seung-Hwan Lee, Ken Dimock, Douglas A Gray, Nicole Beauchemin, Kathryn V. Holmes, Majid Belouchi, John Realson, Silvia M. Vidal. (2003) Maneuvering for advantage: the genetics of mouse susceptibility to virus infection. Trends in Genetics 19:8, 447-457
CrossRef80
K. M. Wegner, T. B. H. Reusch, M. Kalbe. (2003) Multiple parasites are driving major histocompatibility complex polymorphism in the wild. Journal of Evolutionary Biology 16:2, 224-232
CrossRef81
Mary Carrington, Stephen J. O'Brien. (2003) The Influence of HLA Genotype on AIDS*. Annual Review of Medicine 54:1, 535-551
CrossRef82
Linda M. Van Blerkom. (2003) Role of viruses in human evolution. American Journal of Physical Anthropology 122:S37, 14-46
CrossRef83
HUBERT E BLUM, DARIUS MORADPOUR. (2002) Viral pathogenesis of hepatocellular carcinoma. Journal of Gastroenterology and Hepatology 17:s3, S413-S420
CrossRef84
KWANG-HYUB HAN, KYUN-HWAN KIM, HYE YOUNG CHANG. (2002) Immunogenetics of hepatitis B virus infection. Journal of Gastroenterology and Hepatology 17:s3, S329-S332
CrossRef85
Jennifer K. King, Shiou-Hwei Yeh, Ming-Wei Lin, Chun-Jen Liu, Ming-Yang Lai, Jia-Horng Kao, Ding-Shinn Chen, Pei-Jer Chen. (2002) Genetic polymorphisms in interferon pathway and response to interferon treatment in hepatitis B patients: A pilot study. Hepatology 36:6, 1416-1424
CrossRef86
HUBERT E BLUM, DARIUS MORADPOUR. (2002) Antiviral treatment of patients with HBV-related cirrhosis. Journal of Gastroenterology and Hepatology 17:s3, S306-S310
CrossRef87
Thomas Höhler, Esther Reuss, Nina Evers, Evi Dietrich, Christian Rittner, Christine M Freitag, Jens Vollmar, Peter M Schneider, Rolf Fimmers. (2002) Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins. The Lancet 360:9338, 991-995
CrossRef88
Michael Dean, Mary Carrington, Stephen J. O'Brien. (2002) B
ALANCED POLYMORPHISM SELECTED BY GENETIC VERSUS INFECTIOUS HUMAN DISEASE *. Annual Review of Genomics and Human Genetics 3:1, 263-292
CrossRef89
Mehran Ghaderi, Keng-Ling Wallin, Fredrik Wiklund, Liene Nikitina Zake, G
ran Hallmans, Per Lenner, Joakim Dillner, Carani B. Sanjeevi. (2002) Risk of invasive cervical cancer associated with polymorphic HLA DR/DQ haplotypes. International Journal of Cancer 100:6, 698-701
CrossRef90
Ulf P Neumann, Jan M Langrehr, Uta Naumann, Martina Lang, Nada Rayes, Thomas Steinmuller, Cornelia Radtke, Peter Neuhaus. (2002) Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis. Clinical Transplantation 16:2, 122-129
CrossRef91
Yukiya Hakozaki, Makoto Yoshiba, Kazuhiko Sekiyama, Eiji Seike, Junichi Iwamoto, Keiji Mitani, Masafumi Mine, Toshio Morizane, Katsuki Ohtani, Yasuhiko Suzuki, Nobutaka Wakamiya. (2002) Mannose-binding lectin and the prognosis of fulminant hepatic failure caused by HBV infection. Liver International 22:1, 29-34
CrossRef92
Y. Ozawa, J. Chiba, S. Sakamoto. (2001) HLA class II alleles and salivary numbers of mutans streptococci and lactobacilli among young adults in Japan. Oral Microbiology and Immunology 16:6, 353-357
CrossRef93
Mark Thursz. (2001) Genetic susceptibility in chronic viral hepatitis. Antiviral Research 52:2, 113-116
CrossRef94
Mehran Ghaderi, Liene Nikitina Zake, Keng-Ling Wallin, Fredrik Wiklund, Göran Hallmans, Per Lenner, Joakim Dillner, Carani B Sanjeevi. (2001) Tumor necrosis factor A and MHC class I chain related gene A (MIC-A) polymorphisms in Swedish patients with cervical cancer. Human Immunology 62:10, 1153-1158
CrossRef95
Patrice Cacoub, Christophe Renou, Gail Kerr, Sophie H
CrossRef96
Chieko Matsumoto, Kenji Tadokoro, Kayoko Fujimura, Shinichi Hirakawa, Shigeki Mitsunaga, Takeo Juji. (2001) Analysis of HBV infection after blood transfusion in Japan through investigation of a comprehensive donor specimen repository. Transfusion 41:7, 878-884
CrossRef97
J. A. Underhill, M. Mahalingam, M. Peakman, S. Wessely. (2001) Lack of association between HLA genotype and chronic fatigue syndrome. European Journal of Immunogenetics 28:3, 425-428
CrossRef98
P. T. Donaldson, S. Ho, R. Williams, P. J. Johnson. (2001) HLA class II alleles in Chinese patients with hepatocellular carcinoma. Liver International 21:2, 143-148
CrossRef99
Uma Malhotra, Sarah Holte, Sujay Dutta, M. Michelle Berrey, Elizabeth Delpit, David M. Koelle, Alessandro Sette, Lawrence Corey, M. Juliana McElrath. (2001) Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment. Journal of Clinical Investigation 107:4, 505-517
CrossRef100
Victorie Obami-Itou, Mamadou Farba Barry, George Raphenon, Alassane Thiam, Rokhaya Ndiaye, Mouhamadou Ndiaye, Mouhamed Lamine Diaw, Lamine Diakhate, Alioune Dieye. (2000) Serological HLA class I alleles in Senegalese blood donors detected HBs Ag positive. Immunology Letters 74:3, 229-232
CrossRef101
Katie J.M Jeffery, Charles R.M Bangham. (2000) Do infectious diseases drive MHC diversity?. Microbes and Infection 2:11, 1335-1341
CrossRef102
Mei-Hwei Chang. (2000) Hepatitis B Vaccination and Control of Hepatitis B???Related Liver Disease. Journal of Pediatric Gastroenterology and Nutrition 31:2, 112-117
CrossRef103
Janet M. McNicholl, Marie V. Downer, Venkatachalam Udhayakumar, Chester A. Alper, David L. Swerdlow. (2000) Host-Pathogen Interactions in Emerging and Re-emerging Infectious Diseases: A Genomic Perspective of Tuberculosis, Malaria, Human Immunodeficiency Virus Infection, Hepatitis B, and Cholera 1. Annual Review of Public Health 21:1, 15-46
CrossRef104
Basuni, Butterworth, Cooksley, Locarnini, Carman. (2000) An efficient extraction method from blood clots for studies requiring both host and viral DNA. Journal of Viral Hepatitis 7:3, 241-243
CrossRef105
Nizar N. Zein. (2000) Tumor necrosis factor gene promoter polymorphism and recurrent hepatitis C after liver transplantation: The missing link to pathogenesis or a casual association?. Liver Transplantation 6:3, 381-383
CrossRef106
Mark Thursz, Rhiannon Yallop, Robert Goldin, Christian Trepo, Howard C Thomas. (1999) Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The Lancet 354:9196, 2119-2124
CrossRef107
Fabien Zoulim. (1999) Therapy of chronic hepatitis B virus infection: inhibition of the viral polymerase and other antiviral strategies. Antiviral Research 44:1, 1-30
CrossRef108
Douglas G. Mack, Jennifer J. Johnson, Fiona Roberts, Craig W. Roberts, Randee G. Estes, Chella David, F. Carl Grumet, Rima McLeod. (1999) HLA-class II genes modify outcome of Toxoplasma gondii infection. International Journal for Parasitology 29:9, 1351-1358
CrossRef109
Nelson L Michael. (1999) Host genetic influences on HIV-1 pathogenesis. Current Opinion in Immunology 11:4, 466-474
CrossRef110
Adrian V.s. Hill. (1999) The Immunogenetics of Resistance to Malaria. Proceedings of the Association of American Physicians 111:4, 272-277
CrossRef111
C. Mayerat, A. Mantegani, P. C. Frei. (1999) Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?. Journal of Viral Hepatitis 6:4, 299-304
CrossRef112
Rajendra Bhimma, Hoosen Mahomed Coovadia, Anna Kramvis, Miriam Adhikari, Michael Charles Kew, Catherine Anne Connolly. (1999) HBV and proteinuria in relatives and contacts of children with hepatitis B virus-associated membranous nephropathy. Kidney International 55:6, 2440-2449
CrossRef113
Lieven Stuyver, Sija De Gendt, Jean Fran Cadranel, Caroline Van Geyt, Georges Van Reybroeck, Richard Dorent, Iranj Gandjbachkh, Michel Rosenheim, Frederic Charlotte, Pierre Opolon, Jean Marie Huraux, Fran
CrossRef114
Margherita Asti, Miryam Martinetti, Claudo Zavaglia, Maria Clara Cuccia, Laura Gusberti, Carmine Tinelli, Agostino Cividini, Savino Bruno, Laura Salvaneschi, Gaetano Ideo, Mario U. Mondelli, Enrico M. Silini. (1999) Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease. Hepatology 29:4, 1272-1279
CrossRef115
Margaret James Koziel. (1999) What once was lost, now is found: Restoration of hepatitis B-specific immunity after treatment of chronic hepatitis B. Hepatology 29:4, 1331-1333
CrossRef116
Diepolder, Jung, Keller, Schraut, Gerlach, GRUner, Zachoval, Hoffmann, Schirren, Scholz, Pape. (1998) A vigorous virus-specific CD4+ T cell response may contribute to the association of HLA-DR13 with viral clearance in hepatitis B. Clinical and Experimental Immunology 113:2, 244-251
CrossRef117
Sophie Caillat-Zucman, Jean-Jacques Gimenez, Francois Wambergue, Ginette Albouze, Bernard Lebkiri, Catherine Naret, Anne Moynot, Paul Jungers, Jean-Francois Bach. (1998) Distinct HLA class II alleles determine antibody response to vaccination with hepatitis B surface antigen. Kidney International 53:6, 1626-1630
CrossRef118
James W.T.Cohen Stuart, Charles A.B Boucher, David A Cooper, George J Galasso, Douglas D Richman, Howard C Thomas, Richard J Whitley. (1998) Summary of the III International Consensus Symposium on Combined Antiviral Therapy. Antiviral Research 38:2, 75-93
CrossRef119
Richard Bellamy, Dominic Kwiatkowski, Adrian V.S. Hill. (1998) Absence of an association between intercellular adhesion molecule 1, complement receptor 1 and interleukin 1 receptor antagonist gene polymorphisms and severe malaria in a West African population. Transactions of the Royal Society of Tropical Medicine and Hygiene 92:3, 312-316
CrossRef120
Thomas Höhler, Claudius U Meyer, Arman Notghi, Beate Stradmann-Bellinghausen, Peter M Schneider, Roland Starke, Fred Zepp, Roland Sänger, Ralf Clemens, Karl-H.Meyer zum Büschenfelde, Christian Rittner. (1998) The Influence of Major Histocompatibility Complex Class II Genes and T-Cell Vβ Repertoire on Response to Immunization with HBsAg. Human Immunology 59:4, 212-218
CrossRef121
Adrian V. S. Hill. (1998) THE IMMUNOGENETICS OF HUMAN INFECTIOUS DISEASES. Annual Review of Immunology 16:1, 593-617
CrossRef122
HOhler, Kruger, Gerken, Schneider, Meyer Zum BUschenfelde, Rittner. (1998) A tumour necrosis factor-alpha (TNF-alpha) promoter polymorphism is associated with chronic hepatitis B infection. Clinical and Experimental Immunology 111:3, 579-582
CrossRef123
Luigi Greco, Selvaggia Percopo, Fabienne Clot, Faouzi Bouguerra, Marie-Claude Babron, Jean-François Eliaou, Carlo Franzese, Riccardo Troncone, Françoise Clerget-Darpoux. (1998) Lack of Correlation Between Genotype and Phenotype in Celiac Disease. Journal of Pediatric Gastroenterology & Nutrition 26:3, 286-290
CrossRef124
Noriyoshi Kuzushita, Norio Hayashi, Toyoki Moribe, Kazuhiro Katayama, Tatsuya Kanto, Sayaka Nakatani, Toshihiko Kaneshige, Tomohide Tatsumi, Akihiko Ito, Kiyoshi Mochizuki, Yutaka Sasaki, Akinori Kasahara, Masatsugu Hori. (1998) Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus. Hepatology 27:1, 240-244
CrossRef125
Lee, William M., . (1997) Hepatitis B Virus Infection. New England Journal of Medicine 337:24, 1733-1745
Full Text126
Mark A. Schnitzler, Robert S. Woodward, Daniel C. Brennan, Donna L. Phelan, Edward L. Spitznagel, Stuart B. Boxerman, William L. Phelan, Edward L. Spitznagel, Stuart B. Boxerman, William C. Dunagan, Thomas C. Bailey. (1997) Cytomegalovirus and HLA-A, B, and DR locus interactions: Impact on renal transplant graft survival. American Journal of Kidney Diseases 30:6, 766-771
CrossRef127
NURUL AKBAR, BASTAMAN BASUKI, DAVID H GARABRANT, ALI SULAIMAN, HM SJAIFOELLAH NOER. (1997) Ethnicity, socioeconomic status, transfusions and risk of hepatitis B and hepatitis C infection. Journal of Gastroenterology and Hepatology 12:11, 752-757
CrossRef128
H. C. Thomas, J. A. Waters. (1997) Future approaches to treatment of chronic hepatitis B and hepatitis C infection. Journal of Viral Hepatitis 4:s2, 92-97
CrossRef129
H. C. Thomas, M. R. Thursz. (1997) Immunogenetics of hepatitis B virus infection. Journal of Viral Hepatitis 4:s2, 98-100
CrossRef130
Mark R. Thursz, Howard C. Thomas, Brian M. Greenwood, Adrian V.S. Hill. (1997) Heterozygote advantage for HLA class-II type in hepatitis B virus infection. Nature Genetics 17:1, 11-12
CrossRef131
S. Shanmuganathan, J. A. Waters, P. Karayiannis, M. Thursz, H. C. Thomas. (1997) Mapping of the cellular immune responses to woodchuck hepatitis core antigen epitopes in chronically infected woodchucks. Journal of Medical Virology 52:2, 128-135
CrossRef132
JN HANNA, JL FAOAGALI, PJ BUDA, JW SHERIDAN. (1997) Further observations on the immune response to recombinant hepatitis B vaccine after administration to Aboriginal and Torres Strait Island children. Journal of Paediatrics and Child Health 33:1, 67-70
CrossRef133
P. J. Scheuer, S. E. Davies, A. P. Dhillon. (1996) Histopathological aspects of viral hepatitis. Journal of Viral Hepatitis 3:6, 277-283
CrossRef134
Alan Ezekowitz. (1996) Mannose-binding protein and susceptibility to chronic hepatitis B infection. The Lancet 348:9039, 1396-1397
CrossRef135
HC Thomas, GR Foster, M Sumiya, D Mclntosh, DL Jack, MW Turner, JA Summerfield. (1996) Mutation of gene for mannose-binding protein associated with chronic hepatitis B viral infection. The Lancet 348:9039, 1417-1419
CrossRef136
R.G. Batey, S.J. Bollipo. (1996) Hepatitis B. Drug and Alcohol Review 15:3, 289-305
CrossRef137
A. Alexopoulou, P. Karayiannis, S. J. Hadziyannis, J. Hou, J. Pickering, K. Luo, H. C. Thomas. (1996) Whole genome analysis of hepatitis B virus from four cases of fulminant hepatitis: genetic variability and its potential role in disease pathogenicity. Journal of Viral Hepatitis 3:4, 173-181
CrossRef138
Xavier Sastre-Garau, Marie-Noelle Loste, Anne Vincent-Salomon, Michel Favre, Emmanuelle Mouret, Anne de la Rochefordiere, Jean-Claude Durand, Eric Tartour, Virginia Lepagi, Dominique Charron. (1996) Decreased frequency of HLA-DRB 1*13 alleles in Frenchwomen with HPV-positive carcinoma of the cervix. International Journal of Cancer 69:3, 159-164
CrossRef139
Adrian VS Hill. (1996) Genetics of infectious disease resistance. Current Opinion in Genetics & Development 6:3, 348-353
CrossRef140
R.A. Kaslow, M. Carrington, R. Apple, L. Park, A. Muñoz, A.J. Saah, J.J. Goedert, C. Winkler, S.J. O'Brien, C. Rinaldo, R. Detels, W. Blattner, J. Phair, H. Erlich, D.L. Mann. (1996) Influence of combinations of human major histocompatibility complex genes on the course of HIV–1 infection. Nature Medicine 2:4, 405-411
CrossRef141
Peter Karayiannis, Alexandra Alexopoulou, Stephanos Hadziyannis, Mark Thursz, Richard Watts, Seiji Seito, Howard C. Thomas. (1995) Fulminant hepatitis associated with hepatitis B virus e antigen–negative infection: Importance of host factors. Hepatology 22:6, 1628-1634
CrossRef142
Hubert E. Blum, Fritz von Weizsäcker, Stefan Wieland, Silke Offensperger, W.-B. Offensperger. (1995) Antiviral therapy of hepatitis B virus infection: Blocking viral gene expression. Advanced Drug Delivery Reviews 17:3, 321-331
CrossRef143
Moradpour, Darius, Wands, Jack R., . (1995) Understanding Hepatitis B Virus Infection. New England Journal of Medicine 332:16, 1092-1093
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