UMLS:C0019158 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0019158 (hepatitis)
30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA-A,B,DR antigens of two groups, one of normal individuals (N- = 31) and another of CRF (Chronic Renal Failure) patients (K- = 37), who did not develop anti-HBs protective antibodies after Hepatitis B (HB) vaccination, were compared, respectively, to the HLA antigens of two corresponding control groups (N+ = 52, K+ = 49), who responded to the vaccine. A statistically significant difference (Pc less than 0.02) in the frequency of HLA-DR3 was observed between responders and non-responders. An increased frequency of HLA-A1 and HLA-B8 in N- as well as of HLA-A1 and HLA-B35 in K- was also noticed, but this was not of statistical significance. As these antigens have been associated to both HBs antigenemia as well as chronic active hepatitis, we suggest that these genes or other genes in linkage to those may suppress the response to HBV vaccination while, in parallel, they may predispose to an autoimmune course of Hepatitis.
...
PMID:HLA-associated non-responsiveness to hepatitis B vaccine. 234 53

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.
...
PMID:Polymorphism in the human complement C4 genes and genetic susceptibility to autoimmune hepatitis. 785 9

Autoimmune hepatitis is characterized by hypergammaglobulinemia, female predominance, autoantibodies and a good response to immunosuppression, and is based on specific autoantibodies and clinical characteristics. Several subgroups may be distinguished. As in most autoimmune diseases, the etiology is unknown. The association of autoimmune hepatitis with a viral etiology is most prominent in autoimmune hepatitis type 2 which is characterized by liver/kidney microsomal (LKM-1) autoantibodies against cytochrome P-450 II D6. Depending on the geographical origin of the patients, a specific proportion of patients with autoimmune hepatitis type 2 is associated with hepatitis C virus infection. These HCV RNA-positive patients are older, female predominance is not profound, and response to immunosuppression is generally low compared to the HCV-negative patients with autoimmune hepatitis type 2. The genetic background is unclear. HCV sequence analysis revealed that HCV genotype II is prominent in HCV-positive autoimmune hepatitis type 2. HCV mutants with deletions in the HCV envelope region were identified. The relevance of these HCV mutants for the induction of autoimmunity needs to be characterized further. The HCV-negative population of patients with autoimmune hepatitis type 2 seems to have a relation with herpes simplex virus (HSV-1) infection since the B-cell epitope of cytochrome P-450 II D6, the major LKM-1 antigen, shares sequence homology with the IE-175 protein of HSV-1. In the HCV-negative population of autoimmune hepatitis type 2, HLA-DR3 and C4-AQ0 alleles are significantly increased.
...
PMID:Viruses and autoimmune liver disease. 840 37

Human leucocyte antigen (HLA)-typing was studied in 82 hepatitis B carriers and 15 cases of autoimmune hepatitis (AIH) to elucidate the genetic factors which may associated with the etio-pathogenesis of chronic hepatitis in Japan. There were two types of HLA phenotypes: HLA A2 was associated with the progression of the disease induced by HBV infection, and HLA A26 and DR5 were related to the retardation of the disease. A family study confirmed the strong association of these HLA phenotypes with the disease induced by HBV infection. In the analysis of AIH, HLA DR4 is a risk factor related to susceptibility of Japanese AIH which shows different clinical manifestations compared to HLA-DR3-positive AIH, dominantly observed in Western countries. These results suggest that genetic background as expressed by HLA, is an important factor in restricting the development of type B hepatitis and AIH, and can explain racial differences of disease susceptibility.
...
PMID:Immunogenetic background of hepatitis B virus infection and autoimmune hepatitis in Japan. 848 33

An etiopathological link between hepatitis virus infection and autoimmune liver disease, in particular autoimmune hepatitis has been suggested. In some patients features of both viral and autoimmune disease are present. We have studied 352 patients with autoimmune liver disease and 507 patients with viral hepatitis for diagnostic characteristics as well as for evidence of an etiological connection. 38 of the 201 patients with hepatitis C (19%) and 42 of the 306 patients with hepatitis B (14%) had significant titres of autoantibodies (ANA, SMA or LKM). SLA autoantibodies were found exclusively in patients with autoimmune liver disease. LKM auto-antibody was found in only one of the 201 HCV patients. Evidence of past or present hepatitis B virus and past hepatitis A virus infection was most common in the hepatitis C virus patients and least common in autoimmune hepatitis. 28 of the 352 patients with autoimmune liver diseases tested positive in the second generation anti-HCV ELISA, but only five patients (two with autoimmune hepatitis, one with primary sclerosing cholangitis and two with primary biliary cirrhosis) were positive in confirmatory anti-HCV assays, and only in these could HCV-RNA be isolated. Autoimmune hepatitis patients had significantly higher transaminase, GLDH and IgG levels. HLA-B8, HLA-DR3 and HLA-DR4 were significantly more common in autoimmune hepatitis. Distinction between autoimmune liver disease and viral hepatitis C could be made reliably on clinical and laboratory grounds. Our data show that a link between hepatitis A, B, or C virus infection and autoimmune liver diseases is highly unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Relation between autoimmune liver diseases and viral hepatitis: clinical and serological characteristics in 859 patients. 852 56

We have studied the relationship between T-cell receptor (TCR) density, genetic factors and the specific immune response in 153 end stage renal disease (ESRD) patients on haemodialysis immunised with HBsAg vaccine. One-hundred and nineteen patients raised a protective (> 10 U/ml) antibody response to hepatitis-B vaccination (responder, R), while 34 patients were found to be non-responders (NR). The density of the T-cell receptors was determined by flow cytometry. Proliferation of the T-cells induced by autologous monocytes presenting HBsAg was also measured and expressed as a stimulation index (SI). MHC class I, II and III alleles of the patients were also determined. The densities of TCR/CD3 receptors in NR patients were found to be significantly decreased as compared to the R patients (189 +/- 22 vs. 282 +/- 58 arbitrary units, P = 1.3 x 10(-7). TCR/CD3 receptor densities were found to be strongly associated (Spearman correlation coefficient: 0.84, P < 0.000001) with the SI values. Both parameters were found to be under dual genetic control: (a) very low density of the TCR/CD3 receptors and very low SI were found mainly in NR patients carrying HLA-A1, HLA-B8 and HLA-DR3 alleles; and (b) TCR/CD3 densities and function in R group were found to be significantly lower in carriers than in non-carriers of two MHC class III complement protein alleles: C4A*6, and Bf*F. Non-responsiveness to hepatitis-B vaccination was found to be associated with extremely increased neopterin levels. These findings indicate that both genetic and acquired factors contribute to the hepatitis-B vaccination failure in ESRD patients.
...
PMID:Genetic regulation of the impaired immune response to hepatitis-B vaccine associated with low TCR density in end stage renal disease patients: contribution of complement C4 and factor B alleles. 933 52

Susceptibility to autoimmune hepatitis type I (AIH-1) has been associated with HLA-DR3, DR52, and DR4 antigens in Caucasian and Oriental patients. However, in Brazil, disease susceptibility is primarily linked to DR13 and DR52. In this highly admixed population, we find different DR13-associated haplotypes, presenting a unique opportunity to discriminate relevant genes within a tightly linked genomic region. To identify the primary susceptibility locus, we sequenced DR13 alleles of 39 patients with AIH-1 and 22 controls. Patients were almost exclusively DRB1*1301, but half of controls typed DRB1*1302. HLA-DQ haplotypes were varied. Oligotyping of DRB3 locus of all patients and also within the HLA-DR13 positive group showed an allele distribution comparable to controls, confirming that the stronger association lies in the DRB1 locus. On the other hand, if DRB1*1301 is the major susceptibility factor in our sample, the only amino acid different from DRB1*1302 in position 86, corresponding to pocket 1 in the peptide-presenting groove, may be important. We propose that peptide presentation leading to pathogenesis of AIH-1 may be quite stringent, but will also be affected by other strong genetic or environmental susceptibility factors, which would explain the various HLA molecules associated to the disease in the different populations.
...
PMID:Analysis of HLA haplotypes in autoimmune hepatitis type 1: identifying the major susceptibility locus. 1118 27

To determine the frequency, risk factors, and consequences of recurrent autoimmune hepatitis after liver transplantation, 41 patients with type 1 disease were monitored after surgery in accordance with a surveillance protocol. Tacrolimus or cyclosporine plus prednisone were administered to each patient, and liver biopsy examinations were performed at least annually according to protocol. Corticosteroid therapy was ultimately discontinued in only 2 patients. Recurrent disease was defined as the presence of lymphoplasmacytic infiltrates in liver tissue in the absence of other causes of allograft dysfunction. Autoimmune hepatitis recurred in 7 patients (17%), and the mean time to recurrence was 4.6 +/- 1 years. Recurrence was asymptomatic in 4 of 7 patients and detected only by surveillance liver biopsy assessment in 2 patients. Histological changes were mild, and there was no progression to cirrhosis during 4.9 +/- 0.9 years of observation. Five-year patient (86% v. 82%; P =.9) and graft (86% v. 67%; P =.5) survival rates were not statistically different between patients with and without recurrent disease. HLA-DR3 or HLA-DR4 occurred more commonly in patients with than without recurrence (100% v. 40%; P =.008) and healthy subjects (100% v. 49%; P =.01). Recurrent disease was unrelated to donor HLA status. In conclusion, recurrence after transplantation for type 1 autoimmune hepatitis is common. Its mild manifestations and favorable prognosis may reflect early detection by a surveillance protocol and/or continuous corticosteroid treatment. HLA-DR3- or HLA-DR4-positive recipients are at risk for recurrence regardless of donor HLA status.
...
PMID:Recurrent autoimmune hepatitis after orthotopic liver transplantation. 1130 89

Graft dysfunction associated with autoimmune phenomena has been recently described in liver transplant recipients without previous autoimmune disease. However, the natural history, diagnostic criteria, and definitive therapeutic approach of de novo autoimmune hepatitis (de novo AIH) are poorly understood. We report 12 cases of de novo AIH 27.9 +/- 24.5 months after liver transplantation: the outcome of 7 patients treated with steroids is compared with a group of 5 nontreated patients. Nontreated patients lost the graft after 5.8 +/- 2.6 months from de novo AIH onset. All treated patients were alive after 48.4 +/- 14 (29-65) months from de novo AIH onset, and none of them lost the graft. However, 5 patients relapsed in relation to steroid tapering. All patients presented an atypical antiliver/kidney cytosolic autoantibody, associated to classical autoantibodies in 10 cases. Histological study showed several degrees of lobular necrosis and inflammatory infiltrate. HLA antigen frequencies and matching were compared with 2 control groups (16 orthotopic liver transplantation [LTX] patients without de novo AIH and 929 healthy blood donors); de novo AIH patients showed a higher prevalence of HLA-DR3 (54.5% vs. 25.9%, P =.04) than healthy controls, which was not observed in LTX patients without de novo AIH. In conclusion, this new disease should be included in the differential diagnosis of unexplained graft dysfunction. In addition, treatment with steroids results in a dramatically improved outcome. However, maintenance therapy is usually required.
...
PMID:Response to steroids in de novo autoimmune hepatitis after liver transplantation. 1182 8

Autoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by hypergammaglobulinaemia, non-organ and liver-related autoantibodies, association with HLA-DR3 or DR4 and a favourable response to immunosuppression. The current classification of AIH and the several autoantibodies/target autoantigens found in this disease are reported. The importance of these markers in the differential diagnosis and the study of pathogenesis of AIH is also given. AIH is subdivided into two major types: AIH type 1 (AIH-1) and AIH type 2 (AIH-2). AIH-1 is characterised by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Antineutrophil cytoplasmic autoantibodies (ANCA), in most cases of perinuclear pattern (p-ANCA), by the indirect immunofluorescence assay, antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of individuals who are seronegative for ANA/SMA. AIH-2 is characterised by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). For these reasons, the distinction between AIH and chronic viral hepatitis is of particular importance. Cytochrome P450 2D6 (CYP2D6) is the major target autoantigen of anti-LKM-1 autoantibodies in both conditions (AIH-2 and HCV infection). Recent data have demonstrated the expression of CYP2D6 on the surface of hepatocytes, suggesting a pathogenetic role of anti-LKM-1 autoantibodies in liver injury. Family 1 of UDP-glycuronosyltransferases has been identified as the target autoantigen of anti-LKM-3. The molecular target of anti-SLA/LP autoantibodies has been identified recently as a 50 kDa protein with unknown structure and function. A liver-specific enzyme, the formiminotransferase cyclodeaminase, was identified as the target autoantigen of anti-LC1 autoantibodies. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate better with the severity of AIH and the response to treatment. The latter may suggest a pathogenic role of these autoantibodies in the hepatocellular damage in AIH. In general, however, autoantibodies should not be used to monitor treatment or to predict AIH activity or outcome. Finally, current knowledge concerning a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyglandular syndrome type-1 (APS-1), is also discussed. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies found in AIH as a disease component of APS-1. However, anti-LM autoantibodies have also been described in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target autoantigen of anti-LM autoantibodies in both disease entities.
...
PMID:Autoantibodies and defined target autoantigens in autoimmune hepatitis: an overview. 1214 8

1 2 Next >>