Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA antigens were studied among 94 chronic alcoholics. Concerning A and B-loci, there was no significant change of phenotype frequency (PF) in the HLA typing between the patients and controls (80 healthy subjects). However, there was a significant difference in the PF of CW3 between chronic alcoholics and controls (58.5% in alcoholics vs 30.0% in controls). The corrected p value was less than 0.05 with relative risk value being 3.29 HLA-DR loci were also detected in 26 patients, but there was no significant difference between the patients and controls. All alcoholics were subdivided according to the hepatic morphology, and the PF of HLA was examined. A significant high frequency of HLA CW3 was found in patients with hepatitis (64%) compared to controls (30%). There was also an increased PF of CW3 in the liver cirrhosis group (59% in cirrhosis group vs 30% in controls). In conclusion, chronic alcoholics have a significantly higher PF of HLA-CW3 as compared to controls. This characteristic feature becomes even more distinct in alcoholics with severe hepatic lesions.
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PMID:HLA antigens as immunogenetic markers of alcoholism and alcoholic liver disease. 724 36

In 43 cases of chronic active hepatitis of autoimmune-type, HLA-D locus-related antigens (HLA-DR) as well as A and B locus antigens were typed serologically. For 14 patients carrying HLA-B8 and DRw3 family members were typed to establish haplotypes. Control groups consisted of healthy persons and patients with chronic liver disease unrelated to autoimmune CAH (alcoholic cirrhosis and cryptogenic cirrhosis). In autoimmune CAH, DRw3 was significantly increased, 74%, compared with healthy controls, 32%, and liver controls, 31%, this increase being similar to the increase of HLA-B8. There was marked co-occurrence of HLA-B8 and DRw3 in 31 of 33 individuals positive for either antigen. DRw3 was present in 23 of the 24 cases with disease-onset before age 30 hr. HLA typing on the 14 families showed that a haplotype including B8 and DRw3 was present in all index patients; this haplotype also included A1 in 10 cases, A9 in 2 cases, and A2 and A28 in 1 case. The results indicate that in the autoimmune type of chronic active hepatitis occurring characteristically in young females, there exists a disease susceptibility gene strongly associated with the B and D locus of the major histocompatibility complex (MHC), and acting in concert with other non-MHC gene loci and/or environmental factors.
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PMID:HLA associations with autoimmune-type chronic active hepatitis: identification of B8-DRw3 haplotype by family studies. 738 Feb 29

Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena.
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PMID:HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease. 740 Mar 47

HLA antigen determination showed that the frequency of HLA-B40 was significantly increased (49%) in 43 patients with alcoholic cirrhosis, compared with the frequency found in 234 healthy blood donors (18%). The HLA-B40 frequency was not increased in three other patient groups: 36 patients with alcoholic liver disease without cirrhosis (14%), 21 patients with miscellaneous liver disease (24%), and 26 alcoholics without liver disease (24%). We could not confirm the previously reported association between advanced alcoholic liver damage and HLA-B8, which has been taken as support for the relation to autoimmune mechanisms. The association with HLA-B40, however, favours the idea that genetically determined individual susceptibility to alcoholic liver cirrhosis may exist.
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PMID:HLA antigens in alcoholics, with special reference to alcoholic cirrhosis. 743 8

The putative relationship between genetic haemochromatosis and PiZ alpha 1 antitrypsin deficiency was studied using a monoclonal antibody against the PiZ variant in 67 consecutive patients with genetic haemochromatosis seen at Karolinska Hospital and Huddinge University Hospital, Stockholm over a 10 year period. Three (4.5%) of the patients with haemochromatosis were found to be PiZ homozygotes (odds ratio = 82, confidence interval = 26, 256; p < 0.0001). The prevalence of the heterozygous (PiZ) phenotype was similar to that in the general population (p = 0.937). During the ascertainment period, liver biopsy was performed in 65 (97%) of the patients; 66% (2 of 3) of the PiZ homozygotes were found to have cirrhosis compared with 10% (6/59) of the non-carriers of the PiZ variant (p = 0.039). None of the homozygous or heterozygous alpha 1 antitrypsin deficient patients had developed hepatocellular carcinoma compared with 3.4% (2 of 59) of the non-PiZ gene carriers (p = 1.0). Two of those with the homozygous phenotype had developed severe emphysema. HLA typing was performed in 18 patients, 16 (89%) of whom manifested antigens known to be linked to haemochromatosis. There were no significant differences between the PiZ gene carriers and non-carriers in mean age at onset of disease, sex distribution, or HLA type. Two of the PiZ heterozygotes had plasma alpha 1 antitrypsin concentrations below the normal range, though the group mean was lower than that of the non-PiZ carriers (p = 0.0003). The data suggest that the presence of the PiZ allele for alpha1 antitrypsin deficiency, in a double dose, is associated with genetic haemochromatosis and may contribute to the earlier onset of cirrhosis in these patients, though it does not increase the risk of hepatocellular carcinoma.
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PMID:Increased PiZ gene frequency for alpha 1 antitrypsin in patients with genetic haemochromatosis. 761 85

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.
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PMID:[Clinical immunological features and interferon therapy in chronic hepatitis C]. 784 65

Hereditary hemochromatosis is a prevalent inherited disorder with an estimated frequency of homozygosity of 0.2 to 0.45% in Caucasians. The disease is characterized by progressive iron overload until a massive accumulation of body iron occurs. Undetected, the disorder eventually can produce either cirrhosis, diabetes mellitus, cardiac disease, arthritis, or hepatocellular carcinoma or a combination of these manifestations. Early diagnosis and treatment prevents organ damage and normalizes life expectancy. Screening studies to detect hemochromatosis are most effectively accomplished by measurement of the serum iron and total iron binding capacity. Treatment is most effectively performed by frequent phlebotomy until body stores are empty and then 3 to 4 times yearly for life. The basic defect of hemochromatosis appears to increase iron absorption, decrease iron excretion, and produce preferential deposit of iron in hepatic parenchymal cells rather than Kupffer cells. The genetic abnormality of hemochromatosis is located on chromosome 6 in close association with the gene for HLA antigens. Recent speculation postulates that tumor necrosis factor may be involved in the etiology of this disease because of its location on chromosome 6 and its effect upon iron transport.
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PMID:Hereditary hemochromatosis: a prevalent disorder of iron metabolism with an elusive etiology. 794 87

The complement system is an important part of non clonal or innate immunity that collaborates with acquired immunity to kill pathogens and to facilitate the clearance of immune complexes. The complement is made up of 20 distinct plasma proteins and 9 different membrane proteins. Three components, factor B, C2 and C4 (with 2 isotypes), are coded by polymorphic HLA-linked genes and are sometimes referred to as class III antigens, inherited as compact units called complotypes. The C4 genes are the most polymorphic, including a common null allele (Q0) at both the C4A and C4B loci. Other polymorphic complement factors (not linked to HLA) are C3 (2 common alleles), C6 and C7 (closely linked, with 3 and 2 alleles, respectively). A certain degree of polymorphism has also been described for complement receptors and membrane control proteins. No differences in functional activity are usually detected among different alleles. Immune-mediated diseases are associated with C4Q0, in particular: systemic lupus erythematosus and discoid-systemic lupus erythematosus, insulin-dependent diabetes mellitus, liver cirrhosis, celiac disease and IgA/IgG4 deficiency. Even if optimal HLA markers do become available, genetic counselling is usually not the ultimate goal for dealing with most of the HLA-associated common diseases, although their study could help to better delineate disease pathogenesis.
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PMID:Polymorphism of the complement components in human pathology. 794 94

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.
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PMID:[Autoimmune hepatitis]. 817 63

The possible correlation between HLA system and liver cirrhosis secondary to HBV infection has been studied in 102 hospitalized elderly patients affected by liver cirrhosis (histologically proven) and 749 elderly health controls. Increased frequencies of HLA-A2, Cw4, Cw5, DR4, DR5 and DR7 have been observed in patients with liver cirrhosis and previous HBV infection, while a lower frequency of HLA-A2 and higher frequencies of HLA-A3, B35, Cw4, DR3 have been observed in patients without previous HBV infection when compared with controls.
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PMID:HLA-A, B, C and DR in hepatitis B virus (HBV)-related liver cirrhosis: a study of 851 elderly subjects. 818 18


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