Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infant immunization is the most cost-effective strategy to prevent infectious diseases in childhood, but is limited by immaturity of the immune system. To define strategies to improve vaccine immunogenicity in early life, the role of genetic and environmental factors in the control of vaccine responses in infant twins was studied. Immune responses to BCG, polio, hepatitis B, diphtheria, pertussis and tetanus vaccines were measured at 5 months of age in 207 Gambian twin pairs recruited at birth. Intrapair correlations for monozygous and dizygous pairs were compared to estimate the environmental and genetic components of variation in responses. High heritability was observed for antibody (Ab) responses to hepatitis B (77%), oral polio (60%), tetanus (44%) and diphtheria (49%) vaccines. Significant heritability was also observed for interferon-gamma and interleukin-13 responses to tetanus, pertussis and some BCG vaccine antigens (39-65%). Non-HLA genes played a dominant role in responses to Ab-inducing vaccines, whereas responses to BCG were predominantly controlled by genes within the HLA class II locus. Genetic factors, particularly non-HLA genes, significantly modulate immune responses to infant vaccination. The identification of the specific genes involved will provide new targets for the development of vaccines and adjuvants for young infants that work independently of HLA.
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PMID:Genetic regulation of immune responses to vaccines in early life. 1473 96

Vaccination using surface antigen from hepatitis B virus has not been successfully responded by hemodialysis patients. The present study was aimed at assessing a possible relationship between human leukocyte antigens and the low production of protective antibodies (anti-HbS) against the surface antigen from hepatitis B by patients with chronic renal failure submitted to hemodialysis programs. The antigens HLA-DR and HLA-DQ were identified in 76 hemodialysis patients through classic microlymphotoxicity. Our results showed that 34.2% of the patients were non-responsive to the vaccine VHB. The most frequent HLA specificity were: HLA-DR3, DR-7 and DQ2 with a significant association for HLA-DR3 (p=0.0025; OR 5.1; IC 95% 1.36-19.10). Such data suggest an association between genes from HLA class II antigens and the humoral non-response to the vaccine VHB.
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PMID:[Association of humans leucocitary antigens with humoral nonresponsive to hepatitis B vaccine in chronic hemodialysis patients]. 1504 75

Influenza A and B viruses are negative-strand RNA viruses that cause regular outbreaks of respiratory disease and substantially impact on morbidity and mortality. Our primary defense against the influenza virus infection is provided by neutralizing antibodies that inhibit the function of the virus surface coat proteins hemagglutinin and neuraminidase. Production of these antibodies by B lymphocytes requires help from CD4+ T cells. The most commonly used vaccines against the influenza virus comprise purified preparations of hemagglutinin and neuraminidase, and are designed to induce a protective neutralizing antibody response. Because of regular antigenic change in these proteins (drift and shift mutation), the vaccines have to be administered on an annual basis. Current defense strategies center on prophylactic vaccination of those individuals who are considered to be most at risk from the serious complications of infection (principally individuals aged >65 years and those with chronic respiratory, cardiac, or metabolic disease). The clinical effectiveness of influenza virus vaccination is dependent on several vaccine-related factors, including the quantity of hemagglutinin within the vaccine, the number of doses administered, and the route of immunization. In addition, the immunocompetence of the recipient, their previous exposure to influenza virus and influenza virus vaccines, and the closeness of the match between the vaccine and circulating influenza virus strains, all influence the serologic response to vaccination.However, even when these vaccines are administered to young fit adults a proportion of individuals do not mount a significant serologic response to the vaccine. It is not clear whether these nonresponding individuals are genetically pre-programmed to be nonresponders or whether failure to respond to the vaccine is a random event. There is good evidence that nonresponsiveness to hepatitis B vaccine, another purified protein vaccine, is at least partially modulated by an individual's human leucocyte antigen (HLA) alleles. Because CD4+ T cells, which control the neutralizing antibody response to influenza virus, recognize antigens in association with HLA class II molecules, we recently conducted a small study to investigate whether there was any association between HLA class II molecules and nonresponsiveness to influenza virus vaccination. This work revealed that the HLA-DRB1*0701 allele was over represented among persons who fail to mount a neutralizing antibody response. This preliminary finding is important because it potentially identifies a group who may not be protected by current vaccination strategies. Further investigation into the role of HLA polymorphisms and nonresponse to influenza virus vaccination, and vaccination against viruses in general, is clearly required.
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PMID:Human genetics and responses to influenza vaccination: clinical implications. 1546 7

The aim of the study was to investigate whether polymorphisms of the HLA class II, tumour necrosis factor (TNF) and transporter associated with antigen processing (TAP) genes influence the response to alpha-interferon in patients with chronic hepatitis C. Twenty-seven sustained responders and 55 non-responders to alpha-interferon monotherapy were investigated. HLA-DRB1, DQA1, DQB1, TNFA, TNFB, TAP1 and TAP2 alleles were determined by PCR-based molecular techniques. Sustained virological response was defined as undetectable serum hepatitis C virus (HCV) RNA for at least 3 years after the end of treatment. Probability (P) values were corrected for the number of alleles tested (Pc). Viral genotype 1b was more frequent in responders than in non-responders (56% vs. 26%, P = 0.009). HLA-DQB1*02 occurred less frequently in responders than in non-responders (14.8% vs. 29%, Pc not significant). HLA-DRB1*11 and DQB1*0602 were found in 22.2% and 9.3% of responders and in 10.9% and 1.8% of non-responders, respectively (Pc not significant). There was no difference in the distribution of TNF alleles in the two groups. Twenty-four (88.8%) responder patients as compared with 34 (61.8%) non-responders were TAP1*0101 homozygous (Pc not significant). Thus, in European Caucasoids with chronic hepatitis C, we could not demonstrate a strong association between HLA class II, TNF, and TAP gene polymorphisms and response to interferon treatment.
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PMID:Lack of a strong association between HLA class II, tumour necrosis factor and transporter associated with antigen processing gene polymorphisms and virological response to alpha-interferon treatment in patients with chronic hepatitis C. 1554 63

Comparison of human leukocyte antigen (HLA) frequencies in patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients with HCV-associated non-Hodgkin's lymphoma (NHL) has not been addressed previously. To this aim, we investigated the distribution of HLA class II alleles in two selected groups of HCV-infected patients. Group 1 included 50 patients with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A control group included 144 hospitalized patients without NHL or HCC and who were negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies. Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous clearance of HCV infection, was lower in HCC subjects than in controls, whereas HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest different pathogenic pathways in HCC and in NHL development. In patients with HCV-associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11, was found, probably because of a better HLA class II-associated virus clearance. By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated NHL. These data suggest that NHL and HCC development may be associated to a different response with respect to chronic HLA class II-restricted antigen presentation (perhaps a switch toward CD4+Th2 response in NHL?) or, alternatively, that these alleles could be in linkage disequilibrium to unrelated gene(s), or are in synergy with other immunomodulatory genes that may confer increased risk for NHL.
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PMID:Hepatitis C virus-related hepatocellular carcinoma and B-cell lymphoma patients show a different profile of major histocompatibility complex class II alleles. 1555 90

The association of genetic factors with hepatitis B virus (HBV) infection susceptibility, its different manifestations, and the different responses to hepatitis B antigen vaccination have been described by several authors. With regard to HLA class I molecules, association with HLA-B was especially observed.HLA-B35 and -B8 correlated with chronic active hepatitis (CAH)and with hepatitis B carriers. Correlation between HBV infection and HLA class II (loci DR and DQ)was also indicated, but results are not clear regarding the clinical pictures of the disease nor vaccination response. HLA class III (fourth complement component--C4,third complement component--C3, and properdin factor--BF) are associated with various manifestations of this disease. The gammaglobulin phenotype Gm (1,2,3,10,21)was more frequent in CAH. However, in only three publications was the impact of HLA on the efficacy of interferon therapy taken into account.
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PMID:Influence of genetic factors on the susceptibility to HBV infection, its clinical pictures, and responsiveness to HBV vaccination. 1592 82

Recombinant hepatitis B (HB) vaccines have successfully reduced infection, cirrhosis and carcinoma, but questions have endured about causality of serious adverse events following vaccination. After an event in a pediatric patient an investigation reviewed HLA vaccine response effects and analyzed genetics in reported cases. There are apparent common causal immune mechanisms among reported adverse events. HLA class II alleles/haplotypes linked to HB vaccine cellular/non-response and Crohn's disease can create conditions that actively/passively amplify, respectively, all or other components of the immune response to the HB vaccine. Presence of the HLA class I allele A2 can result in heavy cytotoxic T-cell activation and vaccine/self-peptide presentation to immune cells. If HLA autoimmune susceptibility alleles/haplotypes are present that control other immune response components, the probability is elevated that these will activate cross-reactive immune cells; the cells, their inflammatory secretions and/or auto-antibodies may initiate adverse events reflecting those susceptibilities. Probable DRB1 amplifying alleles are noted. High-resolution DNA typing and results analysis are described to test the hypothesis in known HB vaccine adverse event patients. Possible practical applications stemming from hypothesis validation are described.
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PMID:Concurrent HLA-related response factors mediate recombinant hepatitis B vaccine major adverse events. 1604 Mar 39

A 61-year-old man was observed to develop type 1 diabetes mellitus following a 3-month treatment with recombinant alpha-2b peginterferon combined with ribavirin for chronic hepatitis C. Serum samples, collected before the start of therapy and 2 months after the diagnosis of diabetes mellitus, revealed islet-cell antibodies at a titer of 20 and 40 JDF-U, respectively, and glutamic acid decarboxylase autoantibodies at a value of 76.5 and 196 IU/ml, respectively. Antibodies to second islet autoantigen were persistently negative. HLA class II typing revealed the presence of DRB1*04/DRB1*14, DQA1*0303-0104 and DQB1*04-0503 alleles. Eight months after the onset of type 1 diabetes mellitus, the patient is still receiving 30 IU insulin daily; the liver function tests are normal and serum hepatitis C virus RNA is negative. These data confirm that, in patients with potential diabetes mellitus, the disease may become manifest as a side-effect during therapy with peginterferon-alpha plus ribavirin. The patient as a candidate for interferon treatment should therefore be investigated, in addition to thyroid autoimmunity, also for pancreatic autoantibodies before starting therapy.
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PMID:Onset of type 1 diabetes mellitus during peginterferon alpha-2b plus ribavirin treatment for chronic hepatitis C. 1670 61

Hepatitis A is still the most frequently reported vaccine preventable disease. A reduction in the incidence will only be achieved by routine childhood vaccination rather than by targeted vaccination of high-risk groups. A larger vaccine program is warranted. Hepatitis B remains a large public health problem. Vaccination targeted to high-risk adults failed to decrease the incidence of hepatitis B virus (HBV) infection. Sexual as well as nosocomial transmission remain serious problems. Vaccine escape variants have also been identified in newborns from infected mothers who had been vaccinated at birth. Clearance of HBV infection results from complex immune mechanisms including TH1 cytokines significantly associated with HLA class II alleles. Escape HBV mutants, especially precore mutants, influence the outcome. The sequences of the promoter and other critical regions were associated with severe activity. Lamivudine is a major advance in therapy of chronic hepatitis B which was recently approved in many countries. Although drug resistant mutants may be selected during therapy, additional nucleoside analogues including adefovir are promising. Optimal combination strategies of different active compounds need to be researched. Three per cent of the world population has been infected with hepatitis C virus (HCV). Epidemiology has shifted from transfusion to non-transfusion settings. Intravenous drug abuse is currently the main risk but nosocomial infection is also of concern. Three independent factors seem associated with fibrosis progression: age, daily alcohol consumption of 50 g or more and male gender. Median duration of progression to cirrhosis is about 30 years. At the cirrhotic stage, about 3-5% of patients per year develop hepatocellular carcinoma. There is little evidence that direct cytopathicity plays a significant role in liver cell injury. HCV also infects extrahepatic cells which seems critical in the pathogenesis of the many extrahepatic manifestations. The recent identification of CD81 protein as one of the HCV receptor candidates may help us to understand how chronic HCV infection may trigger a wide spectrum of clinical manifestations, autoimmune or even lymphoproliferative, through potent continuous B cell activation in the context of various host and/or environmental cofactors. Direct measurement of HCV RNA has clarified HCV replication kinetics and variability. Among patients with chronic hepatitis C, 48 weeks of treatment with interferon/ribavirin therapy produced a response rate of 28% among those with genotype 1 and 66% with other genotypes. Similar differences were found for combination therapy among patients who had relapsed following previous interferon (IFN) therapy. Viral load prior to treatment has been clearly shown to be predictive of response to interferon treatment, with increased viral load associated with decrease rates of response. In patients non-responsive to interferon, a second course of interferon alone has no beneficial effect whereas combination therapy may induce response in 25%. In conclusion, combination therapy should be given in all situations. Viral eradication should not be the only objective of the treatment since histological improvement may be obtained despite persisting viral replication with prolonged maintenance of antiviral therapy.
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PMID:Viral hepatitis. 1703 15

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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PMID:Association between hepatitis B virus infection and HLA-DRB1 genotyping in Shaanxi Han patients in northwestern China. 1725 20


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