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)

The concept of auto-immune hepatitis as a disease entity evolved from the descriptions of 'chronic active hepatitis' (CAH) in the 1950s. Several types of CAH are distinguished by disease-specific features. The distinctive (but not exclusive) markers for auto-immune CAH include: a negative test for HBsAg; female; Northern European ethnic background; multisystem disease expression; histological CAH with large areas of periportal piecemeal necrosis and plasmacytosis; pronounced hypergammaglobulinaemia; serum auto-antibodies the HLA B8-DR3 phenotype; responsiveness to corticosteroid therapy; and rarity of supervening hepatocellular carcinoma. Much weight is attached to the serological marker auto-antibodies to nuclear or smooth muscle (actin) antigens (ANA, SMA). However, these auto-antibodies do not have an absolute association with auto-immune CAH: the serological reactions are not yet standardized; titres decrease with remission of disease; and other auto-antibodies mark variant forms of auto-immune hepatitis. A more confident acceptance of auto-immune hepatitis as an entity requires detection of a liver-specific antigen, a valid experimental disease model in animals, and a better understanding of immune-mediated damage to liver cells.
 ...
PMID:Auto-immune (lupoid) hepatitis: an entity in the spectrum of chronic active liver disease. 210 17

Homozygosity for alpha 1-antitrypsin deficiency, usually of the genotype PIZZ, is one of the more common single gene defects in infants of European origin, occurring in about 1 in 2000 to 1 in 7000 of the newborn population. About 17% of such infants present with neonatal hepatitis and a small number with intracranial haemorrhage thought to be caused by vitamin K deficiency associated with cholestasis. At least 3% of PIZZ infants will die of cirrhosis in later childhood unless successfully treated by liver transplant. The pathogenesis of the liver disease is not understood and this is unsatisfactory both for treatment and for genetic counselling. The locus coding for alpha 1-antitrypsin (alpha 1AT) is designated PI for proteinase inhibitor. Careful study of the genotypes at this locus in neonatal disease shows that the only certain association is with the homozygous PIZZ genotype. The mutation results in a normal rate of synthesis of a polypeptide that becomes entrapped in the endoplasmic reticulum of the hepatocyte. Some other factor (or factors), as yet unidentified, determines whether severe liver damage results. The low level of alpha 1AT in the plasma seems unlikely to be the primary cause of damage but may play a secondary role. There is some evidence that the other factor(s) may be familial since in one study, though not in all, a high correlation for severity of liver disease was found between PIZZ siblings. The heterogeneity of the clinical course does not result from heterogeneity of PIZ alleles and there is no evidence that it is determined by variation in other related genes on chromosome 14. Only two possible clues have emerged so far. There is some evidence of a protective effect of breast-feeding, and a recent study has found the HLA class II DR3 antigen to be more common than expected in children with alpha 1-antitrypsin deficiency and liver disease. Accumulation of alpha 1AT protein in the hepatocytes may predispose them to some unidentified alteration of the immune response. It is possible that lack of antiprotease activity in the plasma might exacerbate the original damage, so the possibility of useful therapy with alpha 1AT cannot be ruled out entirely. At present, there is no valid way of predicting the severity of disease in a PIZZ child; hence, it is common for parents of a severely affected child to wish to terminate any future PIZZ pregnancy. The most direct method to diagnose the PIZZ genotype of a chorion villus sample is by allele-specific hybridization or sequencing of amplified DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Genetics of alpha 1-antitrypsin deficiency in relation to neonatal liver disease. 218 61

A patient suffering from chronic hepatitis exhibited severe transfusion reactions after administration of fresh frozen plasma and a plasma fraction: PPSB (prothrombin complex concentrate). 1 month before these reactions, she received fresh frozen plasma during plasma exchange therapy. The patient's serum obtained 1 week and 6 months after the second reaction gave a precipitation arc against PPSB preparations when examined by double-diffusion technique in agarose gel. An antibody of IgG class present in these sera reacted with a purified preparation of the fourth complement component (C4). This was demonstrated by various experiments (protein A radioimmunoassay and passive hemagglutination) using purified C4 as antigen. The antibody had a limited specificity and reacted only with C4 of Rodgers specificity. Phenotype determination of the patient's C4 group showed that she was Chido positive and Rodgers negative. Her HLA group was A1, Aw30; B8,-; DR3,-. The patient had neither detectable anti-IgA nor other anti-immunoglobulin antibodies. She had not received blood or plasma transfusion before her hepatitis. The coexistence of a precipitating anti-C4 antibody and adverse transfusion reactions to plasma fractions containing large amounts of C4 indicates that in the absence of antibodies of other specificities, this antibody can be considered as the cause of the transfusion reaction.
 ...
PMID:Adverse transfusion reactions associated with a precipitating anti-C4 antibody of anti-Rodgers specificity. 646 22

An immunogenetic study of autoimmune chronic active hepatitis (CAH) showed the relative risk (RR) for this disease was 11.6 for patients who were HLA-B8, 11.7 for patients who were DR3 and 2.3 for patients who were Gma+x+. Moreover, the Gm haplotype Gma+x+ was present in 18 of 40 (45%) patients with HLA-B8, but in none of 10 patients negative for HLA-B8, whereas in 180 healthy controls Gma+x+ was evenly distributed among those positive (24%) and negative (18%) for HLA-B8. The RR was lowest in patients lacking HLA-B8 but positive for Gma+x+. Relative to this low-risk group, the risk was increased 39 times in subjects with both HLA-B8 and Gma+x+, 15 times in subjects with HLA-B8 who were not Gma+x+ and twice in subjects who were neither HLA-B8 nor Gma+x+. Statistical analysis indicated that the three-factor effect (disease risk affected by non-additive effects of HLA-B8 and Gma+x+) was significant (P less than 0.01), as were the main effects of HLA-B8 (P less than 0.001) and Gma+x+ (P less than 0.02). Thus in the presence of HLA-B8, genes linked to Gma+x+, an immunoglobulin CH allotype, may contribute to the development of autoimmune chronic active hepatitis; in the absence of HLA-B8 these same genes appear to be inactive. This may indicate interactions between MHC gene products and VH gene products in the presentation and recognition of autoantigen(s) in autoimmune hepatitis.
 ...
PMID:Interaction of HLA and Gm in autoimmune chronic active hepatitis. 724 97

In recent years there has been an increasing interest in the link between susceptibility to autoimmune liver disease and genes of the HLA system, although the role of the DPB1 locus in British patients has only been investigated in autoimmune hepatitis. The aim of the current study was to determine the distribution of DPB1 alleles in a large series of British patients with the two other autoimmune liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis, and compare the allele frequencies obtained with those of a geographically matched control group. Polymerase chain reaction sequence-specific oligonucleotide probing was used to assign 18 DPB1 alleles in 82 patients with primary biliary cirrhosis (PBC), 71 patients with primary sclerosing cholangitis (PSC), and 103 controls. The frequencies of the DPB1 alleles were not significantly different comparing patients and controls. However, two important observations were made. Firstly, in primary sclerosing cholangitis, the previously reported association with the haplotype A1-B8-DR3-DQ2 does not extend to the DPB1 locus, suggesting that the genetic determinants of susceptibility for this disease lie closer to the DRB loci. Secondly, in primary biliary cirrhosis there is evidence that the reported association with DR8-DQB1*0402 includes the DPB1*0301 allele. The weak HLA association reported here is in contrast with recent data from Japan, where susceptibility is strongly linked to a particular amino acid residue encoded by the DPB1*0501 allele. These data clearly demonstrate that the alleles of the DPB1 locus are not associated with susceptibility to or protection from either primary biliary cirrhosis or primary sclerosing cholangitis in British patients.
 ...
PMID:HLA DPB polymorphism in primary sclerosing cholangitis and primary biliary cirrhosis. 770 6

Clinical and immunological findings of 74 patients with chronic hepatitis C have been reported and experiences with interferon-alpha treatment of 31 patients are summarized. In addition, the first results of anti-HCV screening of blood donors are also briefly described. Transfusion in the history was noted in 69% of patients and the time, elapsed from the transfusion to the diagnosis was a mean of 7.15 +/- 8.1 years. Concerning the severity of the liver disease, chronic persistent hepatitis was established in 40%, active hepatitis in 45% and cirrhosis in 15% of the patients, respectively. Cholestasis was recorded in 32% of the cases. A significant elevation of serum immunoglobulin levels was noted in 83%, an antibody to liver specific protein (anti-LSP) has occurred in 80%, cryoglobulinaemia in 44% and circulating immune complexes in 33% of the patients. Natural killer cell activity of peripheral blood mononuclear cells significantly decreased. HLA B8 and DR3 antigens were found with elevated frequency (36.6% and 42.1%). Recombinant interferon-alpha at a weekly dose of 3MU thrice, for six months, has normalized serum alanine aminotransferase in 45% of patients and a sustained remission was found in 26%. The treatment resulted in the clearance of HCV-RNS from the serum in 40% of patients and that well correlated with the complete remission. In the good responders, a decrease in CD4+ cell count and a moderate decrease in CD8+ cell count as well as a transient rise in B cell count were seen during the treatment. Mitogen-induced lymphoproliferative response and natural killer cell activity increased. Predictors of response were as follows: female sex, shorter time elapsed from transfusion, absence of HLA, A1, B8, DR3 and serum anti-HBc negativity. Anti-HCV has been found in 0.33--0.38% of blood donors screened, and it is suggested, that a liver disease accompanied with elevated serum alanine aminotransferase, may be present in about 25-30% of anti-HCV positive symptom-free persons.
 ...
PMID:[Clinical immunological features and interferon therapy in chronic hepatitis C]. 784 65

We conducted a randomized trial comparing expectant management versus immunotherapy with paternal leukocytes to improve obstetric outcome in women with unexplained recurrent abortion. Eligible for the study were women with unexplained recurrent abortion (three or more miscarriages and no live birth), negative findings of immunological screening and no inhibition of the mixed lymphocyte culture. These women were seen for the first time between October 1988 and March 1991 in a network of obstetric departments in Northern Italy. Subjects positive for HLA DR3 or with a partner positive for hepatitis virus B antigen were not eligible. A total of 44 women entered the study. Patients were randomly allocated to immunotherapy (22 women) or expectant management (22 women). Women allocated to immunotherapy were given 200 x 10(6) purified paternal lymphocytes before pregnancy. Median follow-up was 24 months (range 10-39) in the immunotherapy group and 25 months (range 11-38) in the expectant management group. Out of the 22 women randomized to immunotherapy, 16 became pregnant and the corresponding value was 14 in the expectant management group. Spontaneous abortion occurred in six out of the 16 pregnancies observed in the treated women. Among the 14 pregnancies observed in the expectant management group, two aborted and one late fetal death occurred. The cumulative proportions of women who became pregnant over 4 years were 37 and 45% in the immunotherapy and expectant management groups respectively; this difference was not significant. No adverse effect was observed in treated women.
 ...
PMID:Immunotherapy and recurrent abortion: a randomized clinical trial. 796 26

Complete congenital heart block is a serious complication of neonatal lupus erythematosus which most often occurs in children of mothers suffering from connective tissue disease. We report the occurrence of complete congenital heart block associated with autoimmune hepatitis (SLA-positive). A 32-year-old woman was treated for more than 10 years for autoimmune hepatitis (SLA-/ANA-positive) and remained in clinical remission under immunosuppressive therapy. She showed an MHC-haplotype typical for autoimmune hepatitis (A1, B8, DR3). After a normal first pregnancy, an emergency caesarean section was performed in the 32nd week of her second pregnancy because of fetal bradycardia. The child died a few hours after delivery of complete congenital AV-block. Retrospective analysis of the maternal serum showed the emergence of SS-A/Ro-antibodies prior to the second pregnancy. The maternal serum antibodies were reactive with the 52 kD SS-A/Ro-antigen, as demonstrated by immunoblot employing recombinant SSA/Ro-antigen. The occurrence of complete congenital heart block has been shown to be associated with the presence of SS-A/Ro antibodies as well as the MHC-haplotype DR3. With respect to this genetic linkage, pregnant patients with autoimmune hepatitis and the MHC-haplotype DR3 should be examined for the presence of SS-A/Ro-antibodies. They should be closely followed during pregnancy to enable early detection of the development of congenital heart block, as prevention by plasmapheresis plus dexamethasone may be possible at an early stage.
 ...
PMID:Complete congenital heart block in autoimmune hepatitis (SLA-positive). 798 13

Susceptibility to autoimmune hepatitis in white patients is associated with the human leukocyte antigen class II antigens DR3 and DR4. 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. DRB3*0101, which encodes DR52a, predisposed patients most strongly to the disease. It was present in 58% of patients and 25% of controls (corrected P < 0.000005), whereas DQA1*0101 and 0102 conferred protection in males only. The DR4 subtype, DRB1*0401, was raised in the DRB3*0101-negative patients; 81% possessed either DRB3*0101 or DRB1*0401, compared with 42% of controls (corrected P < 0.0000001). These alleles encode the amino acid sequence Leu-Leu-Glu-Gln-Lys-Arg at positions 67 to 72 of the DR beta polypeptide, which was present in 94% of patients and 64% of controls (corrected P < 0.000001) and in all patients who tested positive for autoantibodies to the hepatic asialoglycoprotein receptor. The patients with DRB1*0401 had less severe disease, relapsed less frequently and were first seen significantly later in life than those patients with DRB3*0101; and whereas a single copy of DRB1*0401 predisposed to autoimmune hepatitis, DRB3*0101-associated susceptibility had a dose-related effect. These data provide evidence that specific residues in the DR beta polypeptides predispose to autoimmune hepatitis in white patients and genes linked to DRB3*0101 and DRB1*0401 may determine two clinically distinct disease patterns.
 ...
PMID:Allelic sequence variation in the HLA class II genes and proteins in patients with autoimmune hepatitis. 811 85

Acute and chronic autoimmune hepatitis are uncommon inflammatory liver diseases, mainly occurring in young women, in association with hypergammaglobulinemia and serum autoantibodies. Different types have been described: type 1 characterized by anti-smooth muscle and anti-nuclear antibodies; type 2 characterized by anti-LKM1 antibodies; type 3 characterized by anti-SLA antibodies. Other types, still not clearly defined, may exist. Autoimmune hepatitis are associated with HLA A1 B8 DR3 and HLA DR4. Without any treatment, the disease leads to cirrhosis and, uncommonly, to fulminant hepatitis. Large doses of corticosteroids usually allow to control the disease. Relapse of hepatitis is frequent after corticosteroid withdrawal. Concomitant administration of immunosuppressive agents such as azathioprine allows to reduce corticosteroid dosage and contributes to maintain the remission of the disease. Liver transplantation may be indicated in cases of severe cirrhosis or fulminant hepatitis.
 ...
PMID:[Autoimmune hepatitis]. 817 63


1 2 3 4 5 6 Next >>