Disease relevance of Hepatitis, Autoimmune

• We investigated the in vivo silencing effect of small interfering RNA (siRNA) duplexes targeting the gene Fas (also known as Tnfrsf6), encoding the Fas receptor, to protect mice from liver failure and fibrosis in two models of autoimmune hepatitis [1].
• Hepatitis C virus (HCV) is thought to be involved in the pathogenesis of autoimmune hepatitis (AIH) type 2, which is defined by the presence of type I antiliver kidney microsome autoantibodies directed mainly against cytochrome P450 (CYP)2D6 and by autoreactive liver infiltrating T cells [2].
• METHODS: Sera from 62 patients with autoimmune hepatitis, 37 patients with cryptogenic hepatitis, and 19 patients with chronic hepatitis C were assessed under code by enzyme immunoassay [3].
• Experimental autoimmune hepatitis in mice after immunization with syngeneic liver proteins together with the polysaccharide of Klebsiella pneumoniae [4].
• By logistic regression analysis, the probability of chronic rejection was predicted by: sex and cytomegalovirus match of donor and recipient, the presence of acute rejection, recipient age, transplantation for autoimmune hepatitis or primary biliary cirrhosis, and recipients receiving no azathioprine during the third month after transplantation [5].

High impact information on Hepatitis, Autoimmune

• Azathioprine for long-term maintenance of remission in autoimmune hepatitis [6].
• In most patients with autoimmune hepatitis, remission can be maintained with prednisolone, usually in combination with azathioprine, but the majority of patients have a relapse when treatment is stopped and therefore require long-term therapy [6].
• BACKGROUND & AIMS: Autoimmune hepatitis type 2 (AIH-2), a severe juvenile liver disorder of unknown etiology and pathogenesis, is characterized by liver-kidney microsomal antibody type 1 targeting cytochrome P450IID6 (CYP2D6) and is associated to HLA DRB1*07 [7].
• Progress in type 1 autoimmune hepatitis still requires knowledge of a disease-specific autoantigen(s) involved in T-cell reactivity, although such knowledge in type 2 autoimmune hepatitis, in which the known autoantigen is cytochrome P4502D6, has not yet been integrated into a clearly defined scheme of pathogenesis [8].
• To identify diagnostic autoantibodies for APECED hepatitis, sera from 64 patients with APECED were screened for autoantibodies established in the diagnosis of idiopathic autoimmune hepatitis, and for autoantibodies against 10 cytochrome P450s [9].

Chemical compound and disease context of Hepatitis, Autoimmune

• We report 3 patients with autoimmune hepatitis who either could not tolerate or failed to improve on azathioprine but responded well to 6-mercaptopurine [10].
• Twenty months later, the patient developed autoimmune hepatitis with elevated aspartate aminotransferase and immunoglobulin G and high titer antinuclear antibody as well as corticosteroid dependency, whereas the antimitochondrial antibody disappeared [11].
• Members of the glutathione S-transferase gene family are antigens in autoimmune hepatitis [12].
• Therefore, other immunosuppressive agents have been used to replace glucocorticoids in the long-term treatment of autoimmune hepatitis, including azathioprine, a purine analogue [10].
• Low serum levels of complement and C4 null alleles have been reported in autoimmune hepatitis, but studies have been at the protein level only [13].

Biological context of Hepatitis, Autoimmune

• HCV seems to induce autoimmunity to both GOR (an HCV-specific autoepitope) and LKM-1 (an epitope that is also recognised by autoimmune hepatitis sera of a different cause) [14].
• To analyze the molecular basis of these associations, we used oligonucleotide probes to determine the DRB, DQA and DQB hypervariable nucleotide sequences in 119 patients with autoimmune hepatitis and 177 matched controls [15].
• Reactivity to CYP2D6 and its amino acid sequence 257-269 was significantly more common in autoimmune hepatitis than in HCV infected patients (p < 0.001 and p < 0.0003, respectively) [16].
• RESULTS: Autoimmune hepatitis is a consequence of autoantigen exposure, genetic predisposition, and defective immunoregulatory mechanisms [17].
• Treatment of autoimmune hepatitis was associated with a normalization of GP73 expression, indicating that the initial upregulation was reversible [18].

Anatomical context of Hepatitis, Autoimmune

• This study revealed a highly significant association of autoimmune hepatitis with human leukocyte antigen Bw54 and DR4 in Japanese patients [19].
• Antibodies to a soluble liver antigen/liver pancreas (SLA/LP) appear to be highly specific for the diagnosis of autoimmune hepatitis [20].
• Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis [21].
• In 6 patients with autoimmune hepatitis (55%), myeloperoxidase-negative perinuclear neutrophil cytoplasmic antibodies were detected in high titers [22].
• Hepatocyte GP73 expression was increased in patients with acute and autoimmune hepatitis [18].

Gene context of Hepatitis, Autoimmune

• In the present study we provide evidence that a nitric oxide (NO) derivative of ursodeoxycholic acid (UDCA), NCX-1000 ([2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)phenyl ester]), protects against liver damage in murine models of autoimmune hepatitis induced by i.v. injection of Con A or a Fas agonistic antibody, Jo2 [23].
• In conclusion, HCV+/LKM1+ sera recognize a specific conformational epitope on CYP2D6 between amino acids 254 to 288, the region that contains the major linear epitope in type 2 autoimmune hepatitis patients [24].
• Autoimmune regulator AIRE: evidence for genetic differences between autoimmune hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1 [25].
• HLA-C genes and susceptibility to type 1 autoimmune hepatitis [26].
• BACKGROUND/AIMS: Autoimmune hepatitis has a genetic background associated with different HLA DRB1 alleles depending on the ethnic group [27].

Analytical, diagnostic and therapeutic context of Hepatitis, Autoimmune

• Two patients undergoing liver transplantation for classical end-stage primary biliary cirrhosis (PBC) are described, who went on to develop de novo autoimmune hepatitis (AIH) in the transplanted liver [28].
• None of the 135 control sera from patients with primary sclerosing cholangitis (PSC), chronic autoimmune hepatitis (CAH), systemic lupus erythematosus (SLE), or healthy volunteers showed significant reactivity against pML-MIT3 recombinant fusion protein in the ELISA assay [29].
• Therefore, we used reverse transcription-polymerase chain reaction (PCR) and Southern hybridization to identify cytokine message directly from liver tissue of 11 patients with PBC and 5 patients with autoimmune hepatitis (AI-CAH) [30].
• The immunologic diagnosis of chronic active "autoimmune" hepatitis: distinction from systemic lupus erythematosus [31].
• Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics [32].

References