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)

Susceptibility to autoimmune hepatitis is associated with the HLA-DR3 and DR4 haplotypes, but which genes are directly involved in the pathogenesis, has not been established. Low levels of complement component C4 and elevated frequencies of C4 null allotypes have been described in patients, suggesting that the C4 genes, which are closely linked with the HLA loci, may play a role. We therefore examined restriction fragment length polymorphisms in the C4 and 21-hydroxylase genes, and determined HLA-A and B phenotypes, and HLA-DR, DQ and DP genotypes in a large series of Caucasoid patients with autoimmune hepatitis and matched controls. A DNA deletion of the C4A gene and the 21-hydroxylase A pseudogene was found to be present in 50% of patients compared to 23% of controls (Pc < 0.005, relative risk = 3.3). This increase, however, appears to be due to linkage disequilibrium with HLA-DR52a which was most strongly associated with the disease. Complete C4A deficiency, determined by homozygosity for the deletion increased the risk to 18.1 (16% versus 1%, Pc < 0.005), suggesting an additional role for C4 in disease susceptibility. C4 deletions were associated with an increased mortality and tendency to relapse whilst on treatment but did not correlate with age of onset of disease. Our data suggest that MHC-encoded susceptibility to autoimmune hepatitis is polygenic, involving the HLA-DR genes plus other loci, and C4 deficiency may be a marker of disease susceptibility and/or severity.
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PMID:Polymorphism in the human complement C4 genes and genetic susceptibility to autoimmune hepatitis. 785 9

A case of chronic hepatitis C at the pre-cirrhotic stage complicated with hepatocellular carcinoma is reported. The patient, a 64 year old female, showed elevated levels of serum alkaline phosphatase and immunoglobulin M. Antimitochondrial antibodies were negative by indirect immunofluorescence. Western blotting using beef heart mitochondria and recombinant polypeptides coding for mitochondrial antigens revealed that the patient's serum was positive only for the E2-subunit of the branched chain ketoacid dehydrogenase complex. In the non-neoplastic liver, chronic non-suppurative cholangitis surrounded by epithelioid granuloma, resembling the granulomatous destructive cholangitis of primary biliary cirrhosis, was found. The damaged bile ducts were immunohistochemically minimally positive or ambiguous for HLA-DR, and their expression of the E2-subunit of the pyruvate dehydrogenase complex E2 (PDC-E2) was diffuse or granular, and not typical of primary biliary cirrhosis. There was no bile duct loss, and orcein-positive copper binding granules reflecting chronic cholestasis were negative in periportal hepatocytes. The overall features in this case were consistent with primary biliary cirrhosis presenting an infrequent profile of antimitochondrial antibodies and atypical expression of HLA-DR and PDC-E2 on biliary epithelial cells, with late superimposition on chronic hepatitis C. However, it is also possible that this is a case of chronic hepatitis C with hepatitis-associated bile duct damage accompanied by granulomatous reaction. Either way, this case raises new diagnostic issues in the differential diagnosis of chronic liver diseases presented with granulomatous cholangitis.
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PMID:Granulomatous cholangitis in chronic hepatitis C: a new diagnostic problem in liver pathology. 872 56

The aim was to assess the specificity and functional significance of liver-infiltrating and peripheral blood T cells in chronic hepatitis C. Peripheral blood mononuclear cells hepatitis C virus from 50 of 58 (86.2%) patients with chronic hepatitis C virus infection and 6 of 28 (21.4%) controls showed a proliferative T cell response to at least one of 16 synthetic peptides covering highly conserved regions of the core, envelope (El) and non-structural regions (NS4) of hepatitis C virus. However, six immunodominant peptides were exclusively recognized by the proliferating blood mononuclear cells from 46 patients with chronic hepatitis C virus infection (79.3%). Fine specificity and HLA-restriction were studied with 15 peptide-specific CD4+ T cell lines and 23 T cell clones isolated from liver tissue and peripheral blood of 12 patients with chronic hepatitis C. It was demonstrated that the peptide-specific response of CD4+ T cells was restricted to the presence of autologous accessory cells and HLA-DR and -DP molecules. Eight peptide-specific T cell lines and five T cell clones derived from liver tissue and peripheral blood, released interferon-gamma (200-6600 pg/ml) and tumor necrosis factor-alpha (100-400 pg/ml) and no or little interleukin-4 (< 140 pg/ml) after peptide-specific or mitogeneic stimulation, thus resembling a Th1-like cytokine profile. Patients with active liver disease showed significantly higher proliferative responses to hepatitis C virus core peptides than asymptomatic hepatitis C virus carriers or complete responders to interferon therapy. In conclusion, class II-restricted CD4+ T cell responses to some immunodominant epitopes within the hepatitis core region correlated with disease activity in chronic hepatitis C virus infection. Functionally, liver-infiltrating and peripheral blood T cells released Th1-like cytokines in response to the specific stimulus. Thus, it can be suggested that CD4+ T cells can mediate the pathogenesis of chronic hepatitis C virus induced liver disease.
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PMID:Liver-infiltrating and circulating CD4+ T cells in chronic hepatitis C: immunodominant epitopes, HLA-restriction and functional significance. 887 4

The pathogenesis of biliary atresia (BA) is still unknown. Progression to cirrhosis despite restoration of bile flow by successful portoenterostomy suggests that it is a progressive disease of the liver and biliary tree. Whether immunologic factors play any role in the development of this disease remains uncertain. Aberrant expression of major histocompatibility complex (MHC) Class II antigens of HLA-DR on hepatocytes and biliary epithelium is regarded as important in the progression of hepatocellular and biliary damage mediated by cytotoxic T cells. This study was undertaken to evaluate expression of MHC Class II antigen and macrophage-associated antigens (CD68) in liver of patients with biliary atresia to determine their prognostic usefulness and possible role in the pathogenesis of the disease. Liver biopsy specimens from infants with BA (n = 15), neonatal hepatitis (n = 3), and normal livers (n = 6) were studied using an indirect immunoperoxidase staining using antibodies against MHC Class II antigen and macrophage-associated antigens (CD68) as well as routine H&E and Masson's trichome stain. In patients with biliary atresia, the liver biopsy specimen was obtained at the time of Kasai portoenterostomy. Expression of HLA-DR antigens and CD68 antigens was either absent or minimal in normal liver biopsy specimens. There were a few HLA-DR antigens and a few CD68-positive cells around portal tracts in all patients with neonatal hepatitis and five of the seven biliary atresia patients with successful Kasai portoenterostomy. In contrast, there was strong expression of HLA-DR antigen in bile ductules, inflammatory cells, and adjacent damaged hepatocytes and marked CD68-positive macrophage infiltrate in the portal tracts as well as hepatic lobules in two patients with good prognosis and in all eight patients with bad prognosis. Hepatic expression of MHC Class II antigen and CD68 antigens correlated well with the severity of clinical course in patients with BA and may act as a prognostic factor in these patients.
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PMID:Hepatic overexpression of MHC class II antigens and macrophage-associated antigens (CD68) in patients with biliary atresia of poor prognosis. 912 61

A 27-year-old male suffered from Epstein-Barr virus (EBV)-related liver dysfunction with persistent hypogammaglobulinemia. IgG titers to EBV antigens were significantly high, while other hepatitis markers were negative. Liver biopsy disclosed active intralobular inflammation. Two years later, he manifested persistent fever, leukopenia, effusions and hypoproteinemia, and his general condition worsened progressively. The peripheral blood small lymphocytes predominantly expressed natural killer (NK)-like phenotypes (CD2+, CD7+, CD16+, CD56+). Hepatosplenomegaly and marked elevation of serum lactic dehydrogenase were observed. He died of respiratory failure at the age of 29. At autopsy, the liver (2190 g), spleen (860 g), small bowel and mesenteric lymph nodes showed massive infiltration of large atypical lymphoid cells in close association with hemophagocytic histiocytes. Involvement was mildly noted also in the bone marrow, lungs, gall-bladder and kidneys. The atypical cells belonged to CD30+ activated NK-type cells expressing CD2, cytoplasmic CD3 epsilon, CD7, CD45RO, CD56, HLA-DR and HLA-DQ. T cell receptors (TCR), surface CD3, CD4, CD5 and CD8 were not expressed. Epstein-Barr virus-related small nuclear RNA (EBER1) and Epstein-Barr virus-associated nuclear antigen 1 were detected in the nuclei of a significant number of atypical cells, while EBV-related latent membrane protein-1 was negative. EBER1 was also identified in the nuclei of non-neoplastic small lymphocytes at both biopsy and autopsy. Monoclonal integration of the EBV genome into the lymphoma cells was shown by Southern blot analysis. Clonal rearrangement of TCR was undetectable. Roles of chronic active EBV infection in the development of NK cell-type malignancy resembling malignant histiocytosis are discussed.
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PMID:Epstein-Barr virus (EBV)-induced CD30+ natural killer cell-type malignancy resembling malignant histiocytosis: malignant transformation in chronic active EBV infection associating hypogammaglobulinemia. 921 26

Nonalcoholic steatohepatitis is an increasingly recognized clinicopathologic condition. We report two cases of nonalcoholic steatohepatitis in middle-aged Japanese women whose clinical and laboratory data mimicked autoimmune hepatitis. Histologic findings of both cases were definite steatohepatitis with portal and pericellular fibrosis. Both patients' HLA-DR haplotypes were DR4 and DR2, which are frequently observed in Japanese patients with autoimmune hepatitis. Our cases suggest a diversity in the pathogenesis of nonalcoholic steatohepatitis.
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PMID:Nonalcoholic steatohepatitis masquerading as autoimmune hepatitis. 941 73

Autoimmune polyglandular syndrome type 1 (APS1) is characterized by a variable combination of disease components: (1) mucocutaneous candidiasis; (2) autoimmune tissue destruction; (3) ectodermal dystrophy. The disease is caused by mutations in a single gene called APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy) or AIRE (autoimmune regulator) coding for a putative transcription factor featuring two zinc-finger (PHD-finger) motifs. APS1 shows a penetrance of 100%, lack of female preponderance and lack of association with HLA-DR. Typically, onset of APS1 occurs in childhood and multiple autoimmune manifestations evolve throughout lifetime. Organ-specific autoantibodies associated with hypoparathyroidism, adrenal and gonadal failures, IDDM, hepatitis and vitiligo are discussed, and autoantibody patterns in APS1 patients are compared with autoantibodies in APS type 2 (APS2). APS2 is characterized by adult onset adrenal failure associated with IDDM and/or hyperthyroidism. APS2 is believed to be polygenic, characterized by dominant inheritance and association with HLA DR3.
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PMID:Autoimmune polyglandular syndromes. 989 74

To investigate the significance of HLA-class II, especially DR antigens, in autoimmune hepatitis (AIH), the serum concentrations of soluble HLA-DR antigen (sDR) were measured in 16 patients with AIH. The expression of HLA-DR antigens in the liver tissues of AIH patients was also studied by immunohistochemistry. AIH at diagnosis showed markedly higher serum sDR levels than controls, in which the liver tissues exhibited positive staining of HLA-DR antigens. Seven patients received corticosteroid therapy, in whom the serum sHLA-DR concentration was reduced dramatically from activated to remission stage. In sequentially follow-up cases, sDR correlated well with the disease activity, and also with the change of surface DR expression in the liver. A single major band with a molecular size of 60 kDa was detected, both in patient's sera and in normal control sera, by Western blotting. In conclusions, serum sHLA-DR level could be a marker reflecting immunological activity of the disease.
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PMID:Serum soluble HLA-DR antigens in autoimmune hepatitis. 1068 Jul 46

We retrospectively studied 42 liver biopsy specimens from 39 patients who met serologic and histologic criteria of autoimmune liver diseases. We found 10 cases of overlap syndrome (OLS), 10 autoimmune cholangitis (AIC), 10 primary biliary cirrhosis (PBC), and 9 autoimmune hepatitis (AIH) type 1. The following results were obtained: (1) Granulomas and biliary duct lesions were more prominent in PBC and AIC than in OLS and AIH. (2) Bile duct loss was not observed in AIH cases. (3) Features of hepatocellular damage such as piecemeal necrosis, spotty lobular necrosis, and confluent necrosis, were much more prevalent in OLS and AIH than in PBC and AIC. (4) HLA-DR antigen expression by hepatocytes was more frequent in AIH and OLS, whereas the expression of the same antigen by the bile duct epithelium was more frequent in PBC and AIC. We conclude there is a morphologic spectrum in autoimmune liver diseases, in which PBC forms one end of the spectrum, AIH the other, OLS the middle but closer clinically and histologically to AIH than to PBC, and AIC, which seems to be an antimitochondrial antibody-negative subtype of PBC.
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PMID:A spectrum of histopathologic findings in autoimmune liver disease. 1106 43

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


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