Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) antibodies were measured in 28 patients with auto-immune hepatitis type 1 using six different assay kits, three for C100-3 antibody and three for second generation HCV antibody, and two confirmatory tests to determine the prevalence of HCV infection in auto-immune hepatitis. These patients were confirmed to have human leucocyte antigen DR 4 or 2 which is susceptible to auto-immune hepatitis in Japanese. Of the 28 patients, four (14.3%) were positive for HCV antibody in all assays and reacted positively in at least one of the two confirmatory tests, indicating a true positive finding. Eight were positive for HCV antibody only by the Ortho ELISA kit and were negative in both confirmatory tests. The cut-off level for these results was low and became negative soon after the patients received corticosteroid treatment. Thus, these eight patients are presumed to be false-positive reactors. Hepatitis C virus RNA was detected in the serum of two of the four patients with HCV antibody and in none of 24 patients without HCV antibody. No significant difference was observed between the patients with and without HCV antibody in terms of clinical background, liver function tests and auto-antibodies. Our results showed that the prevalence of a past or present HCV infection in patients with auto-immune hepatitis in Japan is low; thus, auto-immune hepatitis is thought to be distinct from hepatitis type C. However, it is also suggested that HCV infection can potentially trigger auto-immune hepatitis.
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PMID:Low prevalence of hepatitis C virus infection in patients with auto-immune hepatitis type 1. 769 9

Possible associations between particular human leucocyte antigen molecules and immunoallergic hepatitis have been suggested previously (HLA-A11 in halothane hepatitis, HLA-DR6 and DR2 in nitrofurantoin hepatitis, HLA-B8 in clometacin hepatitis). In this study the HLA haplotype was determined in 71 patients with idiosyncratic hepatitis due to different drugs. The prevalence of HLA-A11 was twice as high in the 71 patients in the study (23%) as in controls (12%), but p-values were not significant when corrections were made for the large number of comparisons (n = 39). The prevalences of HLA-DR2, DR6, and B8 were similar in the 71 patients and in controls. When hepatitis due to particular drugs was considered, HLA-A11 was found to be present in six of 12 patients (50%) with hepatitis caused by tricyclic antidepressants, and three of four patients (75%) with diclofenac hepatitis, compared to 12% in controls. HLA-DR6 was present in four of five patients (80%) with chlorpromazine hepatitis, compared to 22% in controls. In conclusion, the HLA phenotype does not contribute significantly to idiosyncratic drug-induced hepatitis considered collectively. Possible associations between some HLA molecules and the hepatotoxicity of certain drugs require further confirmation.
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PMID:Possible role of HLA in hepatotoxicity. An exploratory study in 71 patients with drug-induced idiosyncratic hepatitis. 801 43

In hepatitis C, both susceptibility to infection and the course of disease may depend on differences in the immune response. As the major histocompatibility complex (MHC) plays a crucial role in antigen presentation, we investigated a possible relationship between susceptibility to hepatitis C virus (HCV) infection and human leucocyte antigen (HLA) alleles. Therefore, phenotype frequencies of HLA were compared in 186 anti-HCV positive patients with end-stage renal disease (ESRD) to 328 anti-HCV negative patients with ESRD. HLA class I alleles were determined serologically and HLA class II alleles (DRB1, DQA1, DQB1) by the polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) technique. Additionally, in anti-HCV positive patients we looked for a relationship between the activity of hepatitis C (indicated by elevation of transaminases or the presence of viremia) and HLA determinants. For the three criteria (antibody status, elevation of transaminases and viremia) a significant association to HLA alleles was not found in patients with ESRD. This suggests that neither susceptibility to HCV infection nor the biochemical activity of hepatitis and HCV-RNA positivity seem to be strongly related to HLA status in Caucasian patients with end-stage renal disease.
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PMID:No significant influence of HLA determinants on susceptibility to hepatitis C virus infection in Caucasian patients with end-stage renal disease. 902 18

Considerable evidence suggests that immune mechanisms are involved in the pathogenesis of both hepatitis B and C. Both CD4+ and CD8+ T cell responses to viral antigens are important mechanisms that may be responsible for the hepatocyte damage in hepatitis B and C. CD4+ T cell proliferative responses to hepatitis B core antigen (HBcAg) in terms of stimulation index are correlated with hepatitis activity. These responses can be demonstrated in both adult and paediatric patients, and are more vigorous in patients with acute self-limited hepatitis B than in patients with chronic hepatitis B. Patients with hepatitis C also had a significant CD4+ T cell response to hepatitis C virus (HCV) antigens. These responses are also vigorous in acute hepatitis C with recovery than in those cases that evolve to chronic hepatitis C. In terms of human leucocyte antigen (HLA) class I-restricted, CD8+ cytotoxic T lymphocyte (CTL) response, antigenic peptides derived from HBcAg, hepatitis B surface antigen (HBsAg), and polymerase have been demonstrated as the targets for CTL recognition in hepatitis B patients. Multiple CTL epitopes within both HBsAg and HBcAg can be detected by sensitizing target cells with synthetic peptides. Similar to hepatitis B virus (HBV) infection, multispecific, HCV-specific CTL responses can coexist with an extensive quasispecies of viral variants. The mechanisms of viral persistence in both hepatitis B and C are not yet clarified.
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PMID:T cell mechanisms in the immunopathogenesis of viral hepatitis B and C. 940 42

Hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis delta virus (HDV) are associated with clinically significant chronic infection that may lead to the development of cirrhosis or even hepatocellular carcinoma (HCC). Intervention at the earliest possible stage is needed to prevent such untoward sequelae. Currently, interferon (IFN) is the only approved and widely used agent for the treatment of these infections, including in HBV patients with precore mutant hepatitis or decompensated cirrhosis, but its efficacy is far from satisfactory. Corticosteroid priming has been shown to increase the efficacy of IFN therapy in HBV patients with low abnormal serum transaminase levels, but only a few responders will clear serum hepatitis Bs antigen (HBsAg). Ongoing randomized controlled trials of thymosin alpha 1, lamivudine and famcyclovir have demonstrated encouraging preliminary results. Therapeutic vaccines, such as polypeptides with human leucocyte antigen (HLA)-specific hepatitis B core antigen (HBcAg) epitopes, are under phase II/III clinical trial. For HDV infection, the use of IFN in the early phase of acute superinfection tends to prevent chronic progression. For HCV infection, IFN used at higher doses for a longer period of time is associated with a higher sustained response, but overall it is still not satisfactory. The combined use of ribavirin or corticosteroid priming may improve the effect of IFN therapy by enhancing the durability of the response. Interferon in the acute phase of HCV infection may also prevent chronic progression. There is evidence to suggest that IFN therapy, when associated with response, tends to reduce the risk of cirrhosis or HCC and prolongs survival. There is no doubt that satisfactory treatment of chronic viral infection will require more effective agents and demand optimal treatment strategies, many of which are yet to be found.
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PMID:Current therapeutic trends in therapy for chronic viral hepatitis. 940 57

A 26-year-old female bone marrow transplant (BMT) recipient was hepatitis B surface antigen (HBsAg) and hepatitis B e antibody (HBeAb) positive. The donor, her human leucocyte antigen (HLA)-compatible sister, was HBsAg negative but hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) positive. Twelve weeks post-BMT the patient became HBsAg negative, as determined using a monoclonal antibody-based assay. At 16 weeks post-BMT, HBsAg became undetectable by monoclonal and polyclonal immunoassay with seroconversion to HBsAb; however, at 24 weeks post-BMT the patient again became HBsAg positive. Both the recipient and the donor were retrospectively tested by hepatitis B virus (HBV) polymerase chain reaction (PCR) and found to be positive. The recipient displayed variants at amino acids 4 and 47 of the surface (S) gene prior to BMT. These mutations were not detected 32 weeks post-BMT when the S gene sequence was identical to that of an adr prototype. The donor was found to have four unique amino acid substitutions at positions 30, 98, 101 and 210 of the S gene. However, in vitro-expressed HBsAg from the donor was detected by commercial kits and an immunofluorescence assay, indicating that antigenic alteration did not explain HBsAg negativity. This donor highlights the value of PCR as the gold standard test for current HBV infection. It also demonstrates that discordance between two commercial HBsAg assays may not always be caused by antigenic variants. The second episode of hepatitis may theoretically have been caused by reactivation, selection of an escape mutant by HBsAb, reinfection or recombination. We suggest it was reactivation because none of the donor variants was seen in the recipient post-BMT.
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PMID:Failed adoptive immunity transfer: reactivation or reinfection? 1084 33

Susceptibility to autoimmune hepatitis is associated with particular human leucocyte antigen class II alleles. However, non-HLA genetic factors are likely to be required for development of the disease. Among the candidate genes, the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and CD28 genes, located on chromosome 2q33 in humans, encode a cell surface molecule playing a dominant role in the regulation of T-cell activation. The CTLA-4 and CD28 polymorphisms were investigated in children from 32 families with autoimmune hepatitis (AIH). The transmission/disequilibrium test revealed increased transmission of the (AT)8 (dinucleotide repeat) and A (exon 1) alleles of CTLA-4 gene from heterozygous parents to affected offspring (87.5% and 83.5%) with type 1 AIH, compared with unaffected offspring (50.0% for both, p = 0.009 and 0.02, respectively). In contrast, no deviation in transmission for CTLA-4 polymorphisms was found between type 2 AIH patients and unaffected offspring. No evidence for association was found between CD28 gene polymorphism or D2S72 genetic marker and both types of AIH. This study identified the CTLA-4 gene polymorphism as a non-HLA determinant that predisposes to AIH type 1 in children. The genetic heterogeneity seen in the present study provides a new argument in favor of pathogenic differences between type 1 and type 2 AIH.
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PMID:CTLA-4/CD 28 region polymorphisms in children from families with autoimmune hepatitis. 1175 4

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.
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PMID:Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis. 1196 82

The hepatitis B vaccine is considered to be highly immunogenic and has a good safety profile. In adults, it has a primary non-response rate of 5%-10%. Causes of nonresponse to hepatitis B vaccine include age, sex, obesity smoking. Certain human leucocyte antigen (HLA) phenotypes have been known to be associated with responsiveness to the vaccine, and found to be different in different ethnic groups, such as Caucasians and Orientals. The study was designed to identify the HLA phenotypes that are associated with non-responsiveness to hepatitis B virus (HBV) vaccination amongst a cohort of Indian subjects who agreed to participate in the vaccination programme. The study was offered to 107 volunteers, of whom 102 were found to be negative for HBV markers (hepatitis B surface antigen [HBsAg], anti-HBc, anti-HBe, anti-HBs, hepatitis Be antigen [HBeAg]) . All 102 volunteers were offered recombinant hepatitis B vaccine (20 microg) at 0, 1, and 6 months. Anti-HBs antibody titres were tested on days 90 and 210 of the first vaccine dose. HLA typing was done using standard microlymphotoxicity tests. The seroconversion rate of the hepatitis B vaccine was 86.3% (88/102). Fifteen nonresponders (15/102) and 15 of the 88 responders were randomly selected after age and sex matching for the purpose of studying the HLA phenotypes. HLA subtypes A1, B15, B40, A10 and DQ2 were found to be increased among nonresponders while HLA- A11, C3, DR10, DR51 (p>0.05) were the most common phenotypes amongst the responders. Further studies are needed to characterize the HLA phenotypes amongst the responders in different ethnic groups in India with respect to HBV vaccination.
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PMID:Association of HLA phenotype with primary non-response to recombinant hepatitis B vaccine: a study from north India. 1568 56

The CD4+ T-cell response appears to be important for clearance of hepatitis C virus (HCV) in the majority of individuals. We have recently described a series of human leucocyte antigen (HLA)-DR11-restricted T-cell epitopes derived from HCV proteins which enables distinct populations of memory CD4+ T cells to be detected and counted in all nonviraemic HCV subjects. We examined the case of an HLA-DR11+ recipient of a haematopoietic stem-cell transplant who was concurrently infected with HCV from an HLA-DR11+ donor sibling. An acute HCV hepatitis developed and was treated with type I interferon. After successful viral clearance, the recipient demonstrated a selective lack of HCV epitope-specific CD4+ T cells and absence of serological responses compared with the treated donor. The recipient had no evidence of any nonspecific immunosuppression. The subsequent effects of concurrent infection during immune reconstitution are not known in adult humans, but data from murine models suggest this can lead to a skewing of the T-cell repertoire because of thymic selection. From the above observations, it is plausible that the introduction of foreign viral antigen into the thymus may lead to subsequent acquired central tolerance.
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PMID:Immune tolerance to hepatitis C virus acquired during engraftment of bone marrow transplant. 1625 61


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