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)

A 24-year-old patient was admitted to our hospital because of vertigo, coldness and exercise-dependent pain in the left arm. She reported to have suffered from tuberculosis of the lung and a non-A-non-B hepatitis five years ago. Angiography of the aorta thoracica revealed a complete obstruction of the left arteria (a.) subclavia, stenosis of the a. carotis communis on both sides, of the a. carotis interna and the a. vertebralis on the left side as well as a non-detectable perfusion of the upper and medium segment of the left lung. ESR was elevated with 89/128 mm n.W., a hypochromic anaemia, thrombocytosis, hypalbuminaemia, elevation of alpha 2 and gammaglobulins in serum as well as a reduced quick value were found. AT III and protein C concentrations in plasma were also decreased, whereby protein C activity was reduced additionally. HLA-B-51 was positive. Takayasu's arteriitis was diagnosed by us. High-dose treatment with corticosteroids led to a considerable improvement of the clinical status and laboratory parameters of the patient. As this therapy was not associated with a normalization of protein C and AT III concentrations in plasma, protein C and AT III deficiency could be of significance in the development of Takayasu's arteriitis. Until now protein C and AT III deficiency were not described in patients with Takayasu's arteriitis.
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PMID:[A patient with Takayasu arteritis and protein C and AT III deficiency]. 288 94

There is considerable evidence in favour of genetic factors influencing excessive drinking behaviour and development of alcohol dependence (alcoholism), although readily identified markers of these genes have not been established. In addition, environmental factors undoubtedly play an important role. Although the probability of developing a significant liver disease (alcohol-induced hepatitis with or without cirrhosis) is related to the amount of alcohol ingested, there is a great variation in susceptibility which presumably stems from either genetic or additional environmental influences. The probable linkage of development of severe alcohol-induced liver disease with alleles of the HLA-B locus would suggest the influence of a gene(s) on chromosome 6. Such a gene may determine the rate or type of metabolism of alcohol or, since the immune response genes are present on chromosome 6, may indicate genetically controlled variation in the level of the immune and inflammatory response to alcohol-induced changes in liver membrane antigenicity. Further studies are needed to confirm these associations and to determine the type of factor involved.
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PMID:Genetic factors in determining susceptibility to alcohol dependence and development of alcohol-induced liver disease. 678 10

Both direct viral cytopathic effects and host immune responses appear to be important in the pathogenesis of hepatitis C virus (HCV) infection. Liver transplantation provides a means to explore the role of the immune system in the development of HCV-related liver damage through comparing the natural history of HCV in patients with different degrees of donor-recipient human leukocyte antigen (HLA) matching. We evaluated 36 patients with recurrent hepatitis C viremia following liver transplantation to determine whether hepatocellular injury or progression to bridging fibrosis occur more rapidly when donor and recipients share HLA alleles. HLA typing for the HLA-A and HLA-B loci was performed by serological techniques and PCR-based oligotyping was used to type alleles of the DRB1, DRB3, DQA1, and DQB1 loci. A median of eight liver biopsies, obtained during a median follow-up of 36 months, were reviewed per patient. Donor-recipient sharing of alleles of HLA-DQB1 or DRB1 was associated with more rapid development of recurrent hepatitis by univariate analysis (chi2=5.7, P=0.02 and chi2=5.54, P=0.02 respectively). However, only sharing of HLA-DRB1 alleles was identified as an independent predictor of reduced time to recurrent histologic injury by multivariate analysis (chi2 =5.74, P=0.02). Furthermore, sharing of HLA-DRB3 and histologic evidence of rejection were associated with more rapid progression to bridging fibrosis both by univariate methods (chi2=4.12, P=0.04 and chi2=4.66, P=0.03 respectively), and by multivariate analysis (chi2=13.01, P=0.001). These findings suggest that HLA class II-restricted immune responses may contribute to the pathogenesis of HCV-related liver injury in liver transplant recipients.
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PMID:Donor-recipient sharing of HLA class II alleles predicts earlier recurrence and accelerated progression of hepatitis C following liver transplantation. 986 33

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

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease. Characteristic liver-infiltrating immune cells in portal and periportal areas, hypergammaglobulinemia and typical autoantibodies indicate an ongoing autoimmune reaction against liver self antigens, which lead to irreversible cellular damage and ultimately to severe hepatic failure. A significant part of adult, but not pediatric AIH patients, exhibit concurrent autoimmune diseases, further strengthening the immunological etiology of the disease. Genetic susceptibility to autoimmune hepatitis is strongly associated with HLA-DRB1 alleles. In Caucasian European and North American patients, AIH-1 is associated with the presence of DRB1*0301, DRB3*0101 and DRB1*0401 alleles, while AIH-2 is associated with DRB1*0301 or DRB1*07. In Brazil, the primary susceptibility allele for AIH-1 is DRB1*1301, but a secondary association with DRB1*0301 has also been identified. We looked for additional susceptibility factors in the extended MHC region. We genotyped 107 AIH-1 children and up to 326 healthy subjects for TNFA G-308A, TNFA G-238A, LTA A+252G, LTA A+80C, NFKBIL1 T-63A, BAT1 C-348T, BAT1 G-22C, MICA, and HLA-B polymorphisms. The TNFA-308 A allele was significantly increased in AIH-1 when compared with healthy controls, confirming data from other studies. Linkage disequilibrium analysis was carried out. The ancestral haplotype comprising TNFA-308A, TNFA-238G, LTA+252G, LTA+80C, NFKBIL1-63A, BAT1-348C, BAT1-22C, HLA-B*08, MICA*08 was more common in DRB1*03 positive patients than in controls (40% vs. 14%), showing a seven-fold increased risk for the disease [OR=7.8 (95%CI 2.04-29.9.2, p=0.0021). In contrast, the remaining patients carrying DRB1*03 exhibited varied haplotypes. Finally, a variety of class III haplotypes was also present in HLA-DRB1*13 patients, without a predominant pattern. The most common of the 98 haplotypes present in patients were completely absent in controls. The extended haplotype analysis in this sample of AIH-1 patients highlights not only the genetic diversity present in the Brazilian population, but is also in accordance with the previously documented microdiversity within the MHC region. The present knowledge of AIH suggests that the same or a very similar disease can be induced by yet unknown, but different, triggers followed by presentation on different HLA-DR molecules of the epitopes derived from the corresponding autoantigens, characterizing a much more complex disease than previously thought.
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PMID:Autoimmune hepatitis, HLA and extended haplotypes. 2093 6

Allopurinol is the most commonly prescribed urate-lowering therapy for the management of gout. Serious adverse reactions associated with allopurinol, while rare, are feared owing to the high mortality. Such reactions can manifest as a rash combined with eosinophilia, leukocytosis, fever, hepatitis and progressive kidney failure. Risk factors for allopurinol-related severe adverse reactions include the recent introduction of allopurinol, the presence of the HLA-B(*)58:01 allele, and factors that influence the drug concentration. The interactions between allopurinol, its metabolite, oxypurinol, and T cells have been studied, and evidence exists that the presence of the HLA-B(*)58:01 allele and a high concentration of oxypurinol function synergistically to increase the number of potentially immunogenic-peptide-oxypurinol-HLA-B(*)58:01 complexes on the cell surface, thereby increasing the risk of T-cell sensitization and a subsequent adverse reaction. This Review will discuss the above issues and place this in the clinical context of reducing the risk of serious adverse reactions.
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PMID:Allopurinol hypersensitivity: investigating the cause and minimizing the risk. 2641 94