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Familial hepatocellular carcinoma: 'A model for studying preventive and therapeutic measures'. Ann Med Surg (Lond) 2018; 35:129-132. [PMID: 30305894 PMCID: PMC6172566 DOI: 10.1016/j.amsu.2018.09.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Revised: 07/18/2018] [Accepted: 09/21/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with more than 80% of cases found in endemic areas of hepatitis B such as Africa or East Asia. A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk and poor prognosis. Only limited attention has been given to the role of primary genetic factors in HCC, but scattered anecdotal reports have identified familial aggregations of HCC. This article reviewed the literature on familial hepatocellular carcinoma and suggest that familial HCC may be a good model for studying preventive and therapeutic measures.
Highest risk for HCC occur when a hereditary component acts in concert with hepatitis B virus. Different single nucleotide polymorphisms affect various biological pathways predisposing other risk factors. More extensive investigation of the genetic hypothesis of HCC and its fibrolamellar variant required. Prevention with neonatal vaccination is better than cure.
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2
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Weledji EP, Nsagha DS, Enoworock G, Mouladje M. Familial hepatocellular carcinoma in an endemic area: two case reports. BMC Res Notes 2015; 8:415. [PMID: 26342351 PMCID: PMC4560889 DOI: 10.1186/s13104-015-1366-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 08/18/2015] [Indexed: 01/05/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) usually affects patients aged 50–70 years but earlier onset (25–40 years) may occur in hepatitis B endemic areas. 70–90 % of HCC develop on a background of cirrhosis. However, hepatitis B virus is directly oncogenic and can cause HCC in the absence of cirrhosis. This may represent a major cause of death from late diagnosis in resource-limited areas. Case presentation We report a black African family in which clinical diagnosis of HCC was made on two male siblings in the south west region of Cameroon. Conclusions The highest risk for HCC may occur in families in which a hereditary component may be acting in concert with hepatitis B virus. In all cases of HCC, it is important to screen all first degree relatives to detect early and asymptomatic disease. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1366-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Elroy P Weledji
- Department of Surgery, Faculty of Health Sciences, University of Buea, PO Box 126, Limbe, S.W. Region, Buea, Cameroon.
| | - Dickson S Nsagha
- Department of Public Health, Faculty of Health Sciences, University of Buea, Buea, Cameroon.
| | - George Enoworock
- Department of Pathology, Regional Hospital Buea, Buea, Cameroon.
| | - Maurice Mouladje
- Department of Pathology, Regional Hospital Buea, Buea, Cameroon.
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Abstract
SummaryThe present paper reviews the research lines which have been explored to evaluate to what extent genetic factors are intervening on the mechanism of resistance and susceptibility to leprosy.It presents a critical discussion of the investigations on the familial association of leprosy, familial association of leprosy types, intrafamilial contagion of leprosy, concordance of leprosy in twinpairs, racial differences on leprosy prevalence and lepromatous rate, pedigree studies, association of leprosy to genetic markers, Australia antigen, and dermatoglyphic patterns. Space was also allotted to review family and twin-pair studies on the Mitsuda reaction, as well as to the investigation on the in vitro behaviour of blood macrophages against killed M. leprae.Some areas in which further research on leprosy and genetics may be considered as prioritary are outlined with some detail.
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Hennig BJ, Hall AJ. Host genetic factors in hepatitis B infection, liver cancer and vaccination response: a review with a focus on Africa. THE SCIENCE OF THE TOTAL ENVIRONMENT 2012; 423:202-9. [PMID: 20970823 DOI: 10.1016/j.scitotenv.2010.09.036] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2009] [Revised: 09/21/2010] [Accepted: 09/21/2010] [Indexed: 05/30/2023]
Abstract
The disease burden due to hepatitis B virus (HBV) infection remains significant; 350 million people are infected world-wide, and around half a million deaths each year are due to HBV-related liver disease and hepatocellular carcinoma (HCC). Infant immunisation against infection was introduced in the early 1980s, the vaccine is routinely administered across regions where the disease is endemic and has been shown to be safe and effective. However, the large number of older individuals with persistent infection means that disease will not be reduced significantly for several decades. Furthermore, failure to respond to the vaccination has been observed in about 5% of vaccinees and to date we have limited information on the durability of vaccine protection against infection. Hepatitis B infection and disease pathogenesis are known to be influenced by a number of factors including host genetics factors. This review aims to give an overview of the role of genetic variation in persistent HBV infection and the development of liver disease including HCC. Vaccine-induced immunity is, at least in part, heritable and we also discuss findings on the genetic control of responses to HBV vaccination. The epidemiology of HBV infection differs by world region, as does the genetic makeup of individuals originating from different regions. This review focuses on the situation in Africa, where hepatitis B is highly endemic.
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Affiliation(s)
- Branwen J Hennig
- Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
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Dickie ER, Knight RM, Merten C. Part 3: Ethnographic observations on child care and the distribution of hepatitis B virus in the nuclear family. Med Anthropol 2010; 6:21-36. [DOI: 10.1080/01459740.1982.9987003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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6
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Fletcher GJ, Gnanamony M, Samuel P, Ismail AM, Kannangai R, Daniel D, Eapen CE, Abraham P. Association of mannose-binding lectin polymorphisms and HBV outcome in a South Indian population. Int J Immunogenet 2010; 37:177-84. [PMID: 20193030 DOI: 10.1111/j.1744-313x.2010.00908.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Mannose binding lectin (MBL) is an important innate immune system pattern recognition molecule. The MBL gene polymorphisms are reported to play a crucial role in outcome of hepatitis B virus (HBV) infection. In this study, we ascertained the association of MBL genotypes with HBV outcome in a South Indian population. The MBL gene polymorphisms at codons 52, 54 and 57 of exon I, and promoter polymorphisms at -221 were typed by polymerase chain reaction-sequence specific primer in spontaneously recovered and in chronic HBV group. The allele frequency of codon 52 'C' was significantly higher in chronic HBV group than in the recovered group (98.5% vs. 93.6%; P = 0.003) and codon 52 'T' was significantly higher in recovered group than in the chronic group (6.4% vs. 1.5%; P = 0.003). In multivariate analysis, after adjusting for age, sex and state of origin, codon 52 'CC' and 'CT' genotypes were significantly associated with chronicity and recovery respectively [odds ratio (OR), 0.25; 95% confidence interval (CI), 0.08-0.80, P = 0.02] in co-dominant analyzing models. This was re-affirmed in analysis performed exclusively on Tamil Nadu subjects (OR, 0.23; 95% CI, 0.06-0.93, P = 0.039). The frequency of low/none haplotype (XY/O) was significantly higher in recovered group than in chronic group (15.6% vs 7.5%) and associated with spontaneous recovery (OR, 2.28; 95% CI, 1.04-4.99, P = 0.035). Our results provide preliminary evidence that inheritance of codon 52 genotypes and XY/O haplotype associated with low MBL level substantially determine the outcome of HBV infection in a sympatrically isolated South Indian population.
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Affiliation(s)
- G J Fletcher
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
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7
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Wang P, Wang X, Cong S, Ma H, Zhang X. Mutation analyses of integrated HBV genome in hepatitis B patients. J Genet Genomics 2009; 35:85-90. [PMID: 18407055 DOI: 10.1016/s1673-8527(08)60013-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2007] [Revised: 06/04/2007] [Accepted: 06/04/2007] [Indexed: 10/22/2022]
Abstract
Little has been learnt in the last 30 years about detection of HBV genome as well as its mutation analysis between hepatitis B fathers (HBF) and their children. In this study, we used nest polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and DNA sequencing analysis, to examine the integrated HBV genome in paraffin-embedded testis tissues, which were taken as samples from HBF, and in peripheral blood mononuclear cells (PBMC) from 74 cases of HBFs and their children who were born after their fathers' HBV infection (caHBF). We found that HBV DNA existed in testis tissues, mainly in the basilar parts of the seminiferous tubules, and also in PBMC of HBF. It was also documented that there were point mutations of poly-loci, insertions and deletions of nucleotides in integrated HBV genomes, and the types of gene mutations in the HBFs were similar to those in caHBF. This study addresses the major types of gene mutations in integrated HBV genome in human patients and also presents reliable evidence of possible genetic transmission of hepatitis B.
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Affiliation(s)
- Peilin Wang
- Laboratory of Medical Genetics, Medical College of Qingdao University, Qingdao, China
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8
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Liu J, Li Y, Chen T, Yang Y, Wang K, He Y, Yang Q, Ye F, Jin Y, Qiu T, Lin S, Liu M, Zhao Y. The distribution of HBV genotypes and clinical significance in familial clustering in an infected population with unfavorable prognosis. Arch Virol 2008; 153:2157-61. [PMID: 18982245 DOI: 10.1007/s00705-008-0239-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2008] [Accepted: 09/29/2008] [Indexed: 01/05/2023]
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Yang G, Liu J, Han S, Xie H, Du R, Yan Y, Xu D, Fan D. Association between hepatitis B virus infection and HLA-DRB1 genotyping in Shaanxi Han patients in northwestern China. ACTA ACUST UNITED AC 2007; 69:170-5. [PMID: 17257320 DOI: 10.1111/j.1399-0039.2006.00744.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Hepatitis B virus (HBV) infection is a major public health problem worldwide. The mechanism of susceptibility to chronic persistent HBV infection is not well clarified, while the outcome of HBV infection mainly depends on the host immune response. Human leukocyte antigen (HLA) class II molecule is an integral component of the immune response on which majority of host genetic studies have concentrated. Many different HLA class II alleles have been demonstrated to play roles in HBV infection. In this study, the association between HBV infection and HLA-DRB1 alleles in Han individuals in northwestern China was studied for the first time. Two hundred and fifty Shaanxi Han individuals were categorized into three different groups: the HBV-infected patient group (n = 108), the spontaneously cleared control group (n = 108) and the unexposed group (n = 34). DRB1*04, DRB1*09, DRB1*12 and DRB1*15 were the most common genotypes in all the groups. The allele frequencies of HLA-DRB1*03 [10.6% of HBV-infected patients vs 3.7% of spontaneously cleared controls, odds ratios (OR) = 3.10, Pc = 0.008, P < 0.05] and HLA-DRB1*07 (17.6% of HBV-infected patients vs 9.3% of spontaneously cleared controls, Pc = 0.016, OR = 2.09, P < 0.05) were markedly higher in the HBV-infected group. But the allele frequencies of HLA-DRB1*15 (6.9% of HBV-infected patients vs 13.4% of spontaneously cleared controls Pc = 0.039, OR = 0.48, P < 0.05) were obviously lower than that of the spontaneously cleared controls. The above data indicate that HLA-DRB1*03 and HLA-DRB1*07 are related to susceptibility to chronic HBV infection, and DRB1*15 is negatively related to persistence to chronic HBV infection among people in northwestern China. Similar results were got for DRB1*03 and 15 alleles between the HBV-infected patients (n = 108) and 46 HBV seronegative spouses of the HBV patients, who were high-risk group for HBV infection. The above results suggest that host HLA class II gene is an important factor in determination of the outcome of HBV infection.
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Affiliation(s)
- G Yang
- State Key Laboratory for Cancer Biology, Department of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China
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Blumberg BS, Hann HWL, Thomas London W, Yin LK. PRECIPITATING ANTIBODIES IN THE SERA OF TRANSFUSED PATIENTS: POSSIBLE CONFUSION WITH ANTI-AU. Int J Immunogenet 2007. [DOI: 10.1111/j.1744-313x.1974.tb00295.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Abstract
Genetic epidemiology researches such as twin studies, family-clustering of hepatitis B virus (HBV) infection studies and ethnic difference studies have provided the evidence that host genetic factors play an important role in determining the outcome of HBV infection. The opening questions include which human genes are important in infection and how to find them. Though a number of studies have sought genetic associations between HBV infection/persistence and gene polymorphisms, the candidate gene-based approach is clearly inadequate to fully explain the genetic basis of the disease. With the advent of new genetic markers and automated genotyping, genetic mapping can be conducted extremely rapid. This approach has been successful in some infectious diseases. Linkage analysis can find host genes susceptible to HBV and is of great clinical importance.
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Affiliation(s)
- Ying-Li He
- Department of Infectious Diseases, the First Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
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12
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Frodsham AJ, Zhang L, Dumpis U, Taib NAM, Best S, Durham A, Hennig BJW, Hellier S, Knapp S, Wright M, Chiaramonte M, Bell JI, Graves M, Whittle HC, Thomas HC, Thursz MR, Hill AVS. Class II cytokine receptor gene cluster is a major locus for hepatitis B persistence. Proc Natl Acad Sci U S A 2006; 103:9148-53. [PMID: 16757563 PMCID: PMC1482581 DOI: 10.1073/pnas.0602800103] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2005] [Indexed: 01/04/2023] Open
Abstract
Persistent hepatitis B virus infection is a major risk factor for hepatocellular carcinoma, the most frequent cancer in some developing countries. Up to 95% of those infected at birth and 15% of those infected after the neonatal period fail to clear hepatitis B virus, together resulting in approximately 350 million persistent carriers worldwide. Via a whole genome scan in Gambian families, we have identified a major susceptibility locus as a cluster of class II cytokine receptor genes on chromosome 21q22. Coding changes in two of these genes, the type I IFN receptor gene, IFN-AR2, and the IL-10RB gene that encodes a receptor chain for IL-10-related cytokines including the IFN-lambdas, are associated with viral clearance (haplotype P value = 0.0003), and in vitro assays support functional roles for these variants in receptor signaling.
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MESH Headings
- Carcinoma, Hepatocellular/virology
- Carrier State
- Cell Line
- Gambia
- Genetic Markers
- Genetic Predisposition to Disease
- Genotype
- Hepatitis B, Chronic/genetics
- Hepatitis B, Chronic/immunology
- Humans
- Linkage Disequilibrium
- Liver Neoplasms/virology
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Multigene Family
- Polymorphism, Genetic
- Receptor, Interferon alpha-beta
- Receptors, Cytokine
- Receptors, Interferon/genetics
- Receptors, Interferon/metabolism
- Receptors, Interleukin/genetics
- Receptors, Interleukin/metabolism
- Receptors, Interleukin-10
- Sequence Analysis, DNA
- Tumor Necrosis Factor-alpha/metabolism
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Affiliation(s)
- Angela J. Frodsham
- The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
| | - Lyna Zhang
- The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
| | - Uga Dumpis
- Medical Research Council Laboratories, Fajara, The Gambia
| | - Nor Azizah Mohd Taib
- Imperial College School of Medicine, St Mary’s Hospital, Praed Street, London W2 1PG, United Kingdom
| | - Steve Best
- The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
| | - Andrew Durham
- Imperial College School of Medicine, St Mary’s Hospital, Praed Street, London W2 1PG, United Kingdom
| | - Branwen J. W. Hennig
- The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
| | - Simon Hellier
- The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
| | - Susanne Knapp
- Imperial College School of Medicine, St Mary’s Hospital, Praed Street, London W2 1PG, United Kingdom
| | - Mark Wright
- Imperial College School of Medicine, St Mary’s Hospital, Praed Street, London W2 1PG, United Kingdom
| | | | - John I. Bell
- The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
| | - Mary Graves
- **Roche Discovery Welwyn, Welwyn Garden City, Herts AL7 3AY, United Kingdom; and
| | | | - Howard C. Thomas
- Imperial College School of Medicine, St Mary’s Hospital, Praed Street, London W2 1PG, United Kingdom
| | - Mark R. Thursz
- Imperial College School of Medicine, St Mary’s Hospital, Praed Street, London W2 1PG, United Kingdom
| | - Adrian V. S. Hill
- The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom
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Comprehensive analysis of class I and class II HLA antigens and chronic hepatitis B virus infection. J Virol 2003. [PMID: 14581545 DOI: 10.1128/jvi.77] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Following an acute hepatitis B virus (HBV) infection, clearance or persistence is determined in part by the vigor and breadth of the host immune response. Since the human leukocyte antigen system (HLA) is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are key determinants of viral clearance. HLA class I and II genes were molecularly typed in 194 Caucasian individuals with viral persistence and 342 matched controls who had cleared the virus. A single class I allele, A*0301 (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.30 to 0.72; P = 0.0005) was associated with viral clearance. The class II allele DRB1*1302 was also associated with clearance (OR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03), but its significance decreased in a multivariate model that included other alleles associated with disease outcome as covariates. B*08 was associated with viral persistence both independently (OR, 1.59; 95% CI, 1.04 to 2.43; P = 0.03) and as part of the conserved Caucasian haplotype A*01-B*08-DRB1*03. The B*44-Cw*1601 (OR, 2.23; 95% CI, 1.13 to 4.42; P = 0.02) and B*44-Cw*0501 (OR, 1.99; 95% CI, 1.22 to 3.24; P = 0.006) haplotypes were also associated with viral persistence. Interestingly, both the B*08 haplotype and DR7, which forms a haplotype with B*44-Cw*1601, have been associated with nonresponse to the HBV vaccine. The associations with class I alleles are consistent with a previously implicated role for CD8-mediated cytolytic-T-cell response in determining the outcome of an acute HBV infection.
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Thio CL, Thomas DL, Karacki P, Gao X, Marti D, Kaslow RA, Goedert JJ, Hilgartner M, Strathdee SA, Duggal P, O'Brien SJ, Astemborski J, Carrington M. Comprehensive analysis of class I and class II HLA antigens and chronic hepatitis B virus infection. J Virol 2003; 77:12083-7. [PMID: 14581545 PMCID: PMC254245 DOI: 10.1128/jvi.77.22.12083-12087.2003] [Citation(s) in RCA: 117] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Following an acute hepatitis B virus (HBV) infection, clearance or persistence is determined in part by the vigor and breadth of the host immune response. Since the human leukocyte antigen system (HLA) is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are key determinants of viral clearance. HLA class I and II genes were molecularly typed in 194 Caucasian individuals with viral persistence and 342 matched controls who had cleared the virus. A single class I allele, A*0301 (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.30 to 0.72; P = 0.0005) was associated with viral clearance. The class II allele DRB1*1302 was also associated with clearance (OR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03), but its significance decreased in a multivariate model that included other alleles associated with disease outcome as covariates. B*08 was associated with viral persistence both independently (OR, 1.59; 95% CI, 1.04 to 2.43; P = 0.03) and as part of the conserved Caucasian haplotype A*01-B*08-DRB1*03. The B*44-Cw*1601 (OR, 2.23; 95% CI, 1.13 to 4.42; P = 0.02) and B*44-Cw*0501 (OR, 1.99; 95% CI, 1.22 to 3.24; P = 0.006) haplotypes were also associated with viral persistence. Interestingly, both the B*08 haplotype and DR7, which forms a haplotype with B*44-Cw*1601, have been associated with nonresponse to the HBV vaccine. The associations with class I alleles are consistent with a previously implicated role for CD8-mediated cytolytic-T-cell response in determining the outcome of an acute HBV infection.
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Affiliation(s)
- Chloe L Thio
- Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
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Abstract
Before Robert Koch's work in the late nineteenth century, diseases such as tuberculosis and leprosy were widely believed to be inherited disorders. Heritability of susceptibility to several infectious diseases has been confirmed by studies in the twentieth century. Infectious diseases, old and new, continue to be an important cause of mortality worldwide. A greater understanding of disease processes is needed if more effective therapies and more useful vaccines are to be produced. As part of this effort, developments in genetics have allowed a more systematic study of the impact that the human genome and infectious disease have on each other.
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Affiliation(s)
- G S Cooke
- Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
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16
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Abstract
Infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) may result in a number of different clinical outcomes. There is strong evidence in HBV infection that host genetic factors play a major role in determining the outcome of infection. A number of approaches may be used to determine the specific genetic factors involved but the principal method which has been used to date is the disease association study. Disease association studies have a number of drawbacks but trials with well-constructed designs and large numbers of cases have recently produced compelling and reproducible results. In particular alleles in the MHC class II loci and interleukin 10 promoter have been demonstrated to influence the outcome of these infections.
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Affiliation(s)
- M Thursz
- Imperial College School of Medicine, St. Mary's Hospital, Norfolk Place, London W2 1NY, UK.
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17
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Bhimma R, Coovadia HM, Kramvis A, Adhikari M, Kew MC, Connolly CA. HBV and proteinuria in relatives and contacts of children with hepatitis B virus-associated membranous nephropathy. Kidney Int 1999; 55:2440-9. [PMID: 10354293 DOI: 10.1046/j.1523-1755.1999.00467.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV)-associated membranous nephropathy (HBVMN) is an important cause of childhood nephrotic syndrome in regions endemic for the virus, but little is understood of the biosocial context in which the disease develops. We evaluated HBV status and proteinuria in family members and household contacts of index children with HBVMN to test the hypothesis that HBV carriage and asymptomatic proteinuria are closely linked and may be causally associated. METHODS Thirty-one black children with biopsy-proven HBVMN were the index cases. One hundred and fifty-two family members and 43 black household contacts were the subjects of the study. We assessed HBV carrier status by testing for HBV antigens and antibodies using enzyme-linked immunosorbent assays (ELISA) and for HBV DNA by using slot-blot hybridization and the polymerase chain reaction. Sequencing of the precore region of HBV was done in a subset of both index cases and subjects. Proteinuria was assessed by measuring the urinary protein/creatinine ratio. RESULTS Seventy-two (37%) of the 195 family members and household contacts were HBV carriers, and 53 (27%) had a protein/creatinine ratio greater than the physiological limit. The frequency of abnormal proteinuria was not significantly different in those with [22 out of 72 (30.5%)] or without [33 out of 104 (32%)] HBV carriage. This lack of association remained when carriers were classified into those who were HBsAg positive only and those with active viral replication (HBsAg and/or HBeAg and/or HBV DNA; P = 0.01). Family members were more predisposed to HBV carriage than household contacts, but abnormal proteinuria was present with equal frequency (P = 0.48). Age had a significant impact on proteinuria, with children less than five years being more likely to have abnormal proteinuria (P = 0.008). The prevalence of abnormal proteinuria in family members and household contacts of the index cases was more than that in community-based controls. The 10 index HBVMN cases and the 14 family members and household contacts who were tested all had HBV of genotype A. CONCLUSION These results suggest that the family members and household contacts of children with HBVMN are at very high risk of HBV carriage; they also have asymptomatic proteinuria at a significantly higher rate than community-based controls. The HBV carrier status was not associated with proteinuria, a finding supported by peak prevalences of proteinuria in those under five years but no corresponding peak for HBV carriage. Proteinuria may indicate glomerular basement membrane dysfunction. Environmental and social factors may underpin development of these two covert disorders, but are insufficient to account for the index cases of HBVMN. The emergence of children with HBVMN from such households additionally depends on unidentified and possibly genetic factors.
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Affiliation(s)
- R Bhimma
- Department of Paediatrics, University of Natal, Durban, South Africa.
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18
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Abstract
AIM 1) To determine the prevalence of hepatitis B in Sydney autopsies and 2) to determine the relationship between seroprevalence, hepatitis B risk factors and histological changes in the liver. METHODS One hundred autopsy subjects were studied for evidence of past or present hepatitis B infection, using RIA to detect the HBV antigens and antibodies in the serum and peroxidase-antiperoxidase technique to detect HBsAg and HBcAg in the liver. Both serum and liver were examined for the presence of HBV DNA. RESULTS Markers of hepatitis B virus infection were detected in either serum and/or liver of 29 subjects. Four subjects (4%) were seropositive for HBsAg. Eight subjects had been recently infected, 7 were chronically infected and 14 had recovered. CONCLUSION The 29% prevalence of HBV infection is higher than expected. In four cases the serum was either free of HBV markers or showed conventional evidence of recovery, yet the liver still contained HBsAg. There were few histopathological changes despite the presence of HBsAg in the liver. The only epidemiological factors possibly predisposing to HBV infection were tattooing and drug abuse.
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Affiliation(s)
- M J Ashwell
- Department of Infectious Diseases, University of Sydney, New South Wales
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19
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Ramia S. Intrafamilial clustering of hepatitis B virus (HBV) infection: study of 10 Saudi families. ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY 1990; 84:623-7. [PMID: 2076040 DOI: 10.1080/00034983.1990.11812518] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
In order to evaluate the extent of intrafamilial clustering of hepatitis B virus (HBV) infection, serological tests for evidence of HBV infection were performed on family members of 10 Saudi children who were found to be HBs Ag-positive. The overall prevalences of carriers (HBs Ag-positive) and exposure (presence of any HBV marker) in the 89 siblings were 17.9 and 34.8%, respectively. In siblings of families where the mother was a carrier, exposure to HBV (51.6%) was higher (chi 2 = 1.99, P = 0.15) than in siblings of families where only the father was a carrier (31.4%) and significantly higher (chi 2 = 5.24, P = 0.02) than in siblings of families where neither of the parents was a carrier but both had previous exposure to HBV infection (17.4%). Our data indicate that mainly horizontal and perhaps perinatal transmission could account for this relatively high level of intrafamilial clustering of HBV infection in Saudi families. These results are important for the development of a strategy for controlling HBV infection in Saudi Arabia and perhaps in similar HBV endemic areas.
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Affiliation(s)
- S Ramia
- Department of Pathology, College of Medicine King Khalid University Hospital, Riyadh, Saudi Arabia
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20
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Iga T, Babona DV, Nurse GT. Province of origin of hepatitis B surface antigen carriers among blood donors in Port Moresby. Asia Pac J Public Health 1989; 3:237-41. [PMID: 2620026 DOI: 10.1177/101053958900300311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
A paper published in the Medical Journal of Australia in 1972 gave a breakdown of Port Moresby blood donors by HBS Ag carrier status and area of origin. It has lately become possible to test whether such geographical subsamples provide reliable evidence of the carrier status in the home areas, and it appears that, except for the Islands provinces, they do not. Traditional lifestyles conduce to the maintenance and spread of the virus, which is much more prevalent in the provinces than in the capital.
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21
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Mota AH, Fainboim H, Terg R, Fainboim L. Association of chronic active hepatitis and HLA B35 in patients with hepatitis B virus. TISSUE ANTIGENS 1987; 30:238-40. [PMID: 3501908 DOI: 10.1111/j.1399-0039.1987.tb01628.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Fifty-one patients with chronic active hepatitis were typed for their HLA-A, B, C, and DR antigens. We observed a significant increase in the antigen frequency of HLA B35 in patients compared with controls.
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Affiliation(s)
- A H Mota
- Centro de Investigaciones Médicas Albert Einstein, Buenos Aires, Argentina
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22
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Abstract
A study of mortality from hepatoma and hepatic cirrhosis was conducted in Taiwan, where their mortality rates are among the highest in the world in 1980 being 26.10 and 8.14 per 100,000 population for males and females, respectively, for hepatoma, and 33.01 and 12.90 for males and females, respectively, for cirrhosis. The secular trends of hepatoma and hepatic cirrhosis death rates have been increasing, especially in males, with consequent increase in the sex ratio. The large difference in mortality rates between males and females and the increasing trends in the sex ratio suggest that other factors besides hepatitis B virus (HBV), are involved in the aetiology of hepatoma and cirrhosis of liver.
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23
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Blumberg BS. Part 2: Hepatitis B infection and human behavior. Med Anthropol 1982; 6:11-9. [PMID: 22273159 DOI: 10.1080/01459740.1982.9987002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- B S Blumberg
- a University Professor of Medicine and Anthropology , University of Pennsylvania
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24
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Sampliner RE, Bias WB, Carney E, Hillis A, Hillis WD. HLA antigens and HBV infection: evaluation in the chronic carrier state and in a large family. TISSUE ANTIGENS 1981; 18:247-51. [PMID: 7344178 DOI: 10.1111/j.1399-0039.1981.tb01388.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
HLA antigens were determined in 65 apparently well chronic carriers of HBsAg, in race-matched controls and in 42 members of a family with a high frequency of hepatitis B virus infection. The only apparent significant association in the chronic carriers was negative, i.e., no HLA-B7 specificities were found among whites. B7 may confer resistance for whites to chronic infection with hepatitis B. In the family neither active (HBsAg) nor prior (anti-HBs) hepatitis B infection was associated with HLA specificities. HLA antigens in this family failed to provide a clue to the genetics of hepatitis B infection.
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25
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Ayoola EA, Ogunbode O, Odelola HA. Congenital transmission of hepatitis B antigen in Nigerians. Arch Virol 1981; 67:97-9. [PMID: 7236012 DOI: 10.1007/bf01314607] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The prevalence rate of HBsAg carrier state in Nigerian pregnant women was determined to be 11.2 per cent. One third of infants born to these carrier mothers had persistent antigenaemia during an eight month follow-up period.
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26
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Walker WG, Hillis WD, Hillis A. Hepatitis B infection in patients with end stage renal disease: some characteristics and consequences. TRANSACTIONS OF THE AMERICAN CLINICAL AND CLIMATOLOGICAL ASSOCIATION 1981; 92:142-151. [PMID: 7025423 PMCID: PMC2279516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Susceptibility to hepatitis B infection appears to be in part genetically determined. The HLA specificity Bw35 is commonly associated with a higher frequency of both transient and persistent hepatitis B surface antigen in the serum. Persistent hepatitis B surface antigenemia occurring in patients with end stage renal disease while on dialysis is associated with a poor prognosis and markedly decreased survival regardless of whether the individual is treated subsequently by chronic dialysis or by transplantation. We conclude that persistent hepatitis B surface antigenemia is not a contraindication to transplantation since outcome is not improved by management on hemodialysis.
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27
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28
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Tong MJ, Weiner JM, Ashcavai MW, Vyas GN. Evidence for clustering of hepatitis B virus infection in families of patients with primary hepatocellular carcinoma. Cancer 1979; 44:2338-4. [PMID: 228843 DOI: 10.1002/1097-0142(197912)44:6<2338::aid-cncr2820440650>3.0.co;2-i] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Family member of 13 patients with hepatitis B surface antigen (HBsAg) positive primary hepatocellular carcinoma (PHC) were tested for the presence of hepatitis B virus-associated antigens and antibodies. Of the 122 members examined, circulating HGsAg was detected in 47 (39%), antibody to HBsAg (anti-HBs) was found in 37 (30%), and antibody to hepatitis B core antigen (anti-HBc) alone was present in 13 (11%). The relatives with the highest frequency of HBsAg positivity were the offspring of the propositus, followed by the nieces and nephews and the grandchildren. Anti-HBs and anti-HBc were detected most often in the spouses and non-blood relatives. Evidence for past and present hepatitis B virus (HBV) infection was more frequently found in the Asian family members when compared to the non-Asians. The e antigen (HBeAg) was present in 38% of the HBsAg positive individuals, including four with PHC; antibody to HBcAg (anti-HBe) was rarely detected. These results indicate that clustering of HBV infection was commonly present in family members of patients with PHC. The HBsAg positive individuals may be major contributors to the endemic pool of the virus, and may themselves be potential cases of chronic active type B hepatitis, cirrhosis, and PHC.
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29
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Blumberg BS. Sex differences in response to hepatitis B virus. I. History. ARTHRITIS AND RHEUMATISM 1979; 22:1261-6. [PMID: 508376 DOI: 10.1002/art.1780221114] [Citation(s) in RCA: 32] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Sex differences related to responses to hepatitis B infection are reviewed. In most human populations there is a higher prevalence of chronic carriers of hepatitis B virus (persistently HBsAg+) among males than females. Females are more likely than males to produce anti-HBs in response to infection. Diseases associated with increased frequencies of carriers are more prevalent among males. The response of parents to hepatitis B virus (HBV) infection appears to affect the sex ratio at birth of their offspring. Couples in which either parent is a carrier have higher sex ratios (higher proportion of males) compared with couples in which neither parent is HBsAg+. Couples in which the mother is anti-HBs+ have children with lower sex ratios than either carriers or uninfected couples.
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30
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Soyano A, Layrisse Z, Layrisse M, Neel JV. Hepatitis--Bs antigen in an isolated Indian population of southern Venezuela: a family study. J Med Genet 1979; 16:201-5. [PMID: 469898 PMCID: PMC1012691 DOI: 10.1136/jmg.16.3.201] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
A genetic analysis of the presence of HBsAg in a population of which 7.2% of the members were positive is presented. Though the ratios of carriers: non-carriers were generally in good agreement with expectation if the carrier state were determined by homozygosity for a single recessive gene, the two examples of mating most critical to a test of the hypothesis, carrier X carrier, yielded 2 normal children among 4 in one family, and one normal child, the only offspring, in the second family. Other investigators have reported similar findings. We conclude that the hypothesis of simple recessive inheritance cannot be sustained.
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31
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Tong MJ, Weiner JM. Lack of supportive evidence for an autosomal recessive inheritance in chronic hepatitis B infections. Dig Dis Sci 1979; 24:286-8. [PMID: 456216 DOI: 10.1007/bf01296542] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Two families with persistent hepatitis B infections are described. The patterns of HBsAG positivity in the parents and offspring are not compatible with the theory that susceptibility to chronic hepatitis B infection is inherited as an autosomal recessive trait.
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32
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Barr A, Black SH, Burrell CJ, Dow B, Macvarish I. Hepatitis Be antigen and antibody in hepatitis B surface antigen positive blood donors. J Clin Pathol 1979; 32:132-5. [PMID: 108319 PMCID: PMC1145597 DOI: 10.1136/jcp.32.2.132] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
In a study of 105 asymptomatic HBsAg positive blood donors, 9 (8.6%) were found to have HBeAg, 38 (36.2%) anti-HBe, and the remaining 58 (55.2%) neither marker detectable by gel diffusion. There was no correlation between HBeAg/anti-HBe status and HBsAg sub-types, Glm allotypes, the presence of anti-Gm, red cell antibodies, or rheumatoid factor. Rheumatoid factor activity could be removed from anti-HBe positive sera without removing anti-HBe activity, indicating that separate entities were involved. HBeAg was found only in donors under the age of 30 (P less than 0.005), while anti-HBe did not show an age-related trend. HBeAg was also found less commonly in donors of blood group A than in the total carrier population (P less than 0.05), indicating an apparent protection in carriers of group A. The blood group distribution for the 105 HBsAg positive donors was similar to that of the general population.
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33
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Smith DG. The genetic hypothesis for the transmission of Australia antigen (HBsAg). AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 1978; 49:257-63. [PMID: 717557 DOI: 10.1002/ajpa.1330490214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Exceptions have been cited which rule against the simple autosomal recessive hypothesis for the transmission of susceptibility to infection with Australia antigen (HBsAg). An attempt is made here to present a genetic model for a complex segregation analysis of a new and unique set of data to test this hypothesis. Regression techniques were used to estimate in four populations, age and sex-specific penetrance levels and the frequency of the gene whose product is hypothesized to be HBsAg. While the genetic hypothesis was not in general supported, observed deviations and their possible causes are discussed.
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34
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Velasco M, González-Cerón M, de la Fuente C, Ruiz A, Donoso S, Katz R. Clinical and pathological study of asymptomatic HBsAg carriers in Chile. Gut 1978; 19:569-71. [PMID: 680591 PMCID: PMC1412024 DOI: 10.1136/gut.19.6.569] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
A clinical, biochemical, and pathological study was performed in 38 chronic HBsAg carriers. The study group is a part of 393 carriers found among 117 705 voluntary blood donors at the National Blood Bank, Hospital del Salvador, Santiago, Chile. None of the 38 carriers had a past history of illicit drug abuse, hepatitis, or work involving a high risk of hepatitis B virus infection. Ten individuals had a normal liver biopsy, 17 reactive non-specific hepatitis, one fatty changes, four chr onic persistent hepatitis, one aggressive hepatitis, two post-necrotic cirrhosis, and three alcoholic cirrhosis. There was not a close correlation between liver function test and liver histology. The most significant laboratory finding was the postivity of alpha fetoprotein in two cases. During the follow-up the two alpha fetoprotein patients presented a hepatocarcinoma 12 and 14 months after admission to the study.
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35
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Eliakim M, Ligumski M, Sandler SG, Zlotnick A. Familial clustering and immune response in family contacts of patients with HBsAg-positive liver cirrhosis. THE AMERICAN JOURNAL OF DIGESTIVE DISEASES 1978; 23:407-12. [PMID: 677091 DOI: 10.1007/bf01072922] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Families of 11 patients with hepatitis B surface antigen (HBsAg)-positive cirrhosis were studied to evaluate the immunologic correlates and extent of intrafamilial HBsAg clustering. Of 76 family contacts, 12 were identified to be asymptomatic carriers of HBsAg and two were diagnosed to have HSsAg-positive cirrhosis. The over-all HBsAg prevalence for the 76 contacts was 18% and that for all 87 members studied 29.0%. Serologic evidence of hepatitis B virus (HBV) infection (either HBsAg, anti-HBs, or both) was detected in 59% of all family members. HBsAg was more prevalent in males (47%) compared with females (16%), and anti-HBs was more prevalent in females (42%) compared with males (18%). Evidence of an immunologic response in clinically unaffected HBsAg-negative family contacts consisted of elevated serum IgG levels (mean 1660 mg/100 ml) and increased prevalence of anti-smooth muscle and antimitochondrial antibodies (16% and 6%, respectively). The prevalence of one or more autoantibodies in all HBsAg-negative family contacts was 20%, and it was higher in females (25%) than in males (13%). The present study demonstrates that HBsAg clustering occurs in families of patients with cirrhosis in the Jerusalem area and indicates that HBsAg-negative family contacts may have increased B-cell activity.
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36
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37
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Hillis WD, Hillis A, Bias WB, Walker WG. Associations of hepatitis B surface antigenemia with HLA locus B specificities. N Engl J Med 1977; 296:1310-4. [PMID: 870825 DOI: 10.1056/nejm197706092962302] [Citation(s) in RCA: 52] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
To test whether HLA histocompatibility phenotypes might be associated with circulating hepatitis B surface antigen (HBsAG), we performed chisquare and Scheffé analyses on findings in 144 renal patients with known HLA types and HBsAg status. A significant relation between locus B HLA type (or types) and HBS antigenemia was demonstrated (P = 0.01, adjusted for dual testing) with positive associations suggested between Bw15, Bw17 and Bw35 types and transient or persistent (or both) antigenemia. The latter associations individually were statistically significant only if multiple testing was disregarded, but the contrast by the Scheffé method between the three implicated specificities and all other specificities was significant, even after adjustment for multiple testing (P less than 0.02). Associations of genetically determined HLA specificities with hepatitis B infection may constitute the basis for previously observed population differences in HBS Ag prevalences, and suggest that susceptibility to hepatitis B infection may be in part genetically determined.
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38
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Mollica F, Musumeci S, Fischer A. Neonatal hepatitis in five children of a hepatitis B surface antigen carrier woman. J Pediatr 1977; 90:949-51. [PMID: 558303 DOI: 10.1016/s0022-3476(77)80565-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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39
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Vierucci A, London WT, De Martino M, Blumberg BS. Neutrophil function in children who are carriers of hepatitis-B surface antigen. Lancet 1977; 1:157-60. [PMID: 64695 DOI: 10.1016/s0140-6736(77)91761-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The functional capacity of neutrophils of twenty children who are chronic carriers of hepatitis-B surface antigen (HBsAg) was investigated by histochemical and quantitative nitroblue tetrazolium tests (N.B.T.), an assay of bactericidal capacity against Encherichia coli, and an immunofluorescence test for HBsAg in neutrophils, The histochemical N.B.T. test showed that there was a higher proportion of stimulated neutrophils in chronic HBsAg carriers than in controls, but HBsAg particles were not detected in these cells. Bactericidal activity was significantly reduced in chronic carriers. If the defects in neutrophil function in the HBsAg carrier children preceded their hepatitis-B infections they could have influenced the development of the carrier state. Newborn infants infected with hepatitis-B virus are likely to become chronic carriers and neutrophil functions in uninfected newborn infants are similar to those seen in these carriers of HBsAg.
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40
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Larouze B, Saimot G, Lustbader ED, London WT, Werner BG, Payet M. Host responses to hepatitis-B infection in patients with primary hepatic carcinoma and their families. A case/control study in Senegal, West Africa. Lancet 1976; 2:534-8. [PMID: 60621 DOI: 10.1016/s0140-6736(76)91792-x] [Citation(s) in RCA: 112] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A case/control study of patients with primary hepatic carcinoma (P.H.C.) and their families was carried out in Dakar, Senegal. 28 P.H.C. cases were matched by age,sex, and ethnic group with 28 controls. Serum was collected from cases, controls, parents (28 mothers, 27 fathers) of cases, parents of controls, 71 siblings of cases, and 58 siblings of controls. Assays of their sera for hepatitis-B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to hepatitis-B core antigen (anti-HBc) produced the following results. (1) Nearly all P.H.C. cases (97%) and controls (93%) had some evidence of infection with hepatitis-B virus (H.B.V.), but the cases were more likely to be anti-HBc(+) and less likely to be anti-HBs(+) than the controls. (2) Most of the mothers of the cases were HBsAg(+) (71%), whereas only 14% of the mothers of controls were HBsAg(+). Lover titres of anti-HBs were less common in the mothers of the cases. (3) None of 27 fathers of cases had detectable anti-HBs, but 13 (48%) of the fathers of controls were anti-HBs(+). (4) Siblings of the P.H.C. cases were more likely to have anti-HBs than either their sibs with P.H.C. or the sibs of the controls. However, sibs of P.H.C. cases had lower titres of anti-HBs than the sibs of the controls. These data are consistent with the hypothesis that the P.H.C. cases were infected with H.B.V. by their mothers and that there was an environmental factor which affected the immunological response of all family members to H.B.V. Infection with H.B.V. and the mode of response to that infection among members of families appear to be major factors in the aetiology of P.H.C. in West Africa.
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41
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Knolle J, Born M, Hess G, Klinge O, Arnold W, Bitz H, Meyer KH. [The characterization of clinically healthy hepatitis-b-surface-antigen (HBsAg)-carriers. Clinical, biochemical, histiological and immunological investigations in 129 case of a prospective study (author's transl)]. KLINISCHE WOCHENSCHRIFT 1976; 54:567-78. [PMID: 781393 DOI: 10.1007/bf01619572] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
129 blood donors found to be HBsAg-positive on routine testing were studied for evidence of hepatic disease. Twelve had already lost the antigen from the serum when histologically examined. None of these has had clinical or histological evidence of inflammatory liver disease. Two of the 129 patients showed mild icteric hepatitis, cleared the antigen during the follow up and became anti-HBs positive. The remaining 115 patients who appeared clinically healthy and who had no history of previous icteric liver disease remained HBsAg positive during a mean follow up period of 17.3 +/- 3.0 months. Forty patients from these had a normal liver histology and 37 mild to distinct steatosis but no signs of inflammatory liver disease. 11 patients a mild nonspecific mesenchymal activity but no focal necrosis, 16 patients had mild infiltration in portal tracts and a few necrotic parenchymal cells with mesenchymal reaction, 6 patients had chronic persistent hepatitis, 4 chronic aggressive hepatitis, and 1 definite posthepatic cirrhosis.
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42
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43
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Meek ES, O'Connor ML. Hepatitis-B: a review. CRC CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES 1976; 7:49-98. [PMID: 60200 DOI: 10.3109/10408367609151687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The recent literature on various aspects of hepatitis-B is reviewed with emphasis on the interrelationships of viral structure, antigenic components, and host immune response in acute, chronic, and asymptomatic carrier states of the infection. The mode of replication and mechanisms of transmission are discussed. Special attention is paid to potential non-parenteral routes of spread. The role of hepatitis-B in associated immune complex diseases and in hepatoma is outlined. A guide to the interpretation of serologic tests for hepatitis-B associated antigen and antibody patterns is presented in relation to the clinical stage and prognosis of the infection. Therapy, except in conceptual terms, is not covered but a summary of the current status of active and passive immunization is given. The unresolved question of the infectivity of carrier medical staff for their patient contacts, and the reverse, is discussed.
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44
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Stevens CE, Beasley RP. Lack of an autosomal recessive genetic influence in vertical transmission of hepatitis B antigen. Nature 1976; 260:715-6. [PMID: 1264244 DOI: 10.1038/260715a0] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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45
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Szmuness W. Recent advances in the study of the epidemiology of hepatitis B. THE AMERICAN JOURNAL OF PATHOLOGY 1975; 81:629-50. [PMID: 1108668 PMCID: PMC2032336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Recent advances in the study of hepatitis B shed much light on the basic epidemiologic patterns of this unique infection. The spectrum of host responses following exposure is unusually wide. Hepatitis B appears to be one of the most widespread infections; the total number of chronic carriers of the hepatitis B antigen has been estimated as at least 120 million. The following factors have been found to be closely associated with the risk of hepatitis B; geography, sex, age at testing, age at primary infection, socioeconomic status, ethnicity, occupation, sharing a household with a carrier, sexual promiscuity, and immunologic responsiveness. Data concerning the infectivity of an asymptomatic carrier are ambiguous; whether a carrier can transmit the virus by sexual intercourse also remains unknown. Available evidence seems to suggest that genetic factors may be of importance in the aggregation and segregation of hepatitis B.
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46
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47
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Abstract
The recent observation by Arndt-Hansen et al. (1974) of increased frequency of blood group A over group O in blood donors positive for the hepatitis associated antigen has been investigated in Down's syndrome, in order to establish if this could account for the increased frequency of the antigen in that syndrome. Seventy-one of 227 subjects with Down's syndrome (31.3%) were found to be positive for the antigen by haemagglutination, and comparison of these with the HAA-subjects failed to reveal any differences in the ABO blood groups.
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48
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Piccinino F, Manzillo G, Sagnelli E, Balestrieri G, Maio G. Familial clustering of hepatitis B antigen and liver diseases in families with a high incidence of viral hepatitis. Infection 1975; 3:99-104. [PMID: 1184196 DOI: 10.1007/bf01641050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
In each of 23 families in which two or more cases of acute hepatitis-like jaundice (index cases) occurred, all family members were studied to evaluate HBAg clustering and the incidence of asymptomatic liver disease. There were 49 "index cases" of hepatitis-like jaundice: 38 cases of acute viral hepatitis, 5 of chronic agressive hepatitis and 6 of active cirrhosis. The overall number of members in these families (excluding index cases) was 170 and 155 of which were tested by clinical examination, laboratory tests and needle liver biopsy. In 27 out of the 155 subjects there was evidence of liver diseases (10 non icteric hepatitis cases, 12 CAH cases and 5 cirrhosis cases). HBAg was present in the serum of 19 of these patients, and twof the cirrhotic patients were positive. Furthermore, 33 of the 155 cases were healthy HGAg carriers showing no abnormality in liver function tests. In the majority of these carriers liver histology showed slight damage (pin-head necrosis or portitis) sometimes compatible with resolving viral hepatitis. A long-term follow-up of the HGAg carriers showed that three of these subjects progressed to acute viral hepatitis.
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49
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Boettcher B, Hay J, Watterson CA, Bashir H, MacQueen JM, Hardy G. ASSOCIATION BETWEEN AN HL-A ANTIGEN AND AUSTRALIA ANTIGEN IN AUSTRALIAN ABORIGINES. ACTA ACUST UNITED AC 1975. [DOI: 10.1111/j.1744-313x.1975.tb00518.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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50
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Abstract
To determine the frequency of vertical transmission of hepatitis B antigen (HB5 Ag) from asymptomatic carrier mothers in Taiwan to their offspring, HB5 Ag was sought by radioimmunoassay and complement fixation. Of 158 babies born to carrier mothers, antigenemia developed in 63; 51 of these antigenemic babies had become antigen positive within the six months of life. Three inter-related factors were found to increase the risk that antigenemia would develop in the infant: a high maternal complement-fixation titer for HB5 Ag: presence of HB5 Ag in the baby's umbilical-cord blood: and antigenemia in siblings. In contrast to previous studies, these findings indicate that vertical transmission from carrier mothers frequently occurs, at least in Taiwan, and may partially explain Taiwan's high prevalence of HB5 Ag.
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