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)

What then are the lessons to be learned about prevention and treatment of hemochromatosis? Early diagnosis is essential. The best indicator would be testing of serum iron and total saturation followed by a serum ferritin if elevated. Once these indices are abnormally high, MRI and or a liver biopsy should confirm the stage of the iron over-loaded state. If indeed the patient is not iron-overloaded (normal liver biopsy in the face of high saturation and ferritin level) phlebotomies should be performed until these indices are normal and then maintained at a normal level. This should entail four to six phlebotomies a year. Family members should also be screened and managed in a like manner. HLA typing may be a partially helpful screening device. The abnormal gene is closely linked on chromosome 6 with HLA histocompatibility loci. Now, by means of HLA typing, we can identify heterozygote carriers and homozygous (abnormal) among first degree relatives of patients with hemochromatosis. Unfortunately, HLA typing can only be used within a given family and cannot be used to screen the general population. It is estimated that 70% of hemochromatoics have the antigen HLA-A3; however, so does 28% of the (well) general population. Patients with unexplained cirrhosis, arthritis, liver disease, diabetes, impotency, cardiomyopathy and neurological symptoms should be screened in a like manner. Routine health practice profile chemistries must include a serum iron and iron saturation, and if high followed by a serum ferritin. Once diagnosed, therapy must be maintained with phlebotomy for the life time of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemochromatosis: diagnosis and treatment. 179 61

The case survey of drug-induced hematologic disorders in Shikoku District (Ehime Prefecture) disclosed 21 patients. Cases were 12 rheumatoid arthritis patients, 2 brain tumor, one epilepsy, 2 liver cirrhosis, one neuralgia, one arthralgia, one hyperthyroidism, and one IBL-like T-lymphoma. Causative drugs for aplastic anemia were Metalcaptase, Shiosol, Voltaren and Emeside. Drug-induced aplastic anemia was so severe that 4 out of 5 patients had died of bone marrow dysfunction. Neutropenia was caused by drugs as Rimatil, Cefobit, Sepatren, Mercazole, Sulpyrin, Aleviatin, Cefamedin and Metalcaptase. The real causes of these drug-induced hematologic disorders have not been clear. Remarkably high incidence among rheumatoid arthritis patients is suggestive several reasons as unique reactivity associated with HLA, suppression on hematologic stem cells by abnormal metabolites, and immunologic dysfunction commonly seen in collagen diseases. Further studies of more accurate incidence of drug-induced hematologic disorders are needed in investigating real causes of unhappy side-effects.
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PMID:[Drug-induced hematologic disorders in Shikoku district]. 192 Aug 31

A 50 year-old patient with sickle cell anemia was seen who had received only two units of blood during his lifetime. He had marked iron overloading, cirrhosis of the liver, arthralgia, and mild glucose intolerance. We believe the iron overloading was associated with hereditary hemochromatosis rather than sickle cell anemia because he had HLA-A3 and B7 antigens, and hepatic iron deposits were primarily in parenchymal cells rather than Kupfer cells. The coexistence of either homozygous or heterozygous hemochromatosis should be suspected in sickle cell patients with organ damage from iron overloading.
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PMID:Sickle cell disease and hemochromatosis. 195 9

Twenty-one patients with primary sclerosing cholangitis were seen during 1979-87. The mean age at onset of disease was 51.7 years (range: 13-78 years) with a male: female ratio of 2.5:1. Six (29%) were asymptomatic at the time of diagnosis. Eleven patients (52%) had ulcerative colitis. Cholangiography demonstrated abnormalities limited to the intrahepatic ducts in 10 cases, with both intrahepatic and extrahepatic involvement in 11. Histological features on liver biopsy included: portal tract inflammation and cholestasis in all; paucity of bile ducts in 56%; piecemeal necrosis in 19% and cirrhosis in 6%. Circulating autoantibodies and elevated serum immunoglobulins were found in half of the patients and HLA-B8 was detected in 53%. A deficiency of circulating CD3 and CD8 cells was not found in the 12 patients tested. The mean follow-up was 51 months (range: 3-180 months). Three patients died from non-hepatic causes and another has received liver transplantation. A Kaplan-Meier curve predicted 70% survival at 72 months.
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PMID:Primary sclerosing cholangitis: clinical and immunopathological review of 21 cases. 210 94

In patients with chronic active hepatitis (CAH), the absence of the conventional serum auto-antibodies (antinuclear, smooth muscle and liver-kidney microsomal) is often taken as evidence against an auto-immune aetiology and as indicative that the disease is unlikely to respond to immunosuppressive therapy. We report 12 British patients (11 female) who presented with histologically florid CAH (11 with cirrhosis or fibrosis and seven with ascites) but without significant titres of these antibodies or any other demonstrable aetiological feature (cryptogenic CAH), who have been followed up for a median of 5.25 years (range: 0.75-16 years). Ten had hypergammaglobulinaemia and/or specific elevations of serum IgG concentrations at presentation and five of 10 patients tested were found to have the HLA allotypes B8 and DR3. Remission was initially induced with prednisolone with or without azathioprine in all patients. Six patients subsequently relapsed on one or more occasions, either spontaneously while on maintenance therapy or during attempts to withdraw corticosteroids, and required increases or reintroduction of immunosuppressive therapy to regain disease control. Retrospective analysis of pretreatment samples from 11 of the patients revealed that all had been seropositive at presentation for auto-antibodies against the liver membrane lipoprotein preparation known as liver-specific membrane lipoprotein (LSP) and/or against the hepatic asialoglycoprotein receptor (ASGP-R), titres of which subsequently fluctuated in direct relation to response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Auto-immune features in patients with idiopathic chronic active hepatitis who are seronegative for conventional auto-antibodies. 210 5

Twelve patients (5 women and 7 men, aged from 19 to 54 years) presenting with congenital, non-spherocytic haemolytic anaemia due to erythrocyte pyruvate kinase (PK) deficiency were investigated for systemic iron overload 18 to 27 years after the diagnosis was made. One patient had, beside PK deficiency, idiopathic haemochromatosis demonstrated by the HLA A3 and B14 markers. Another, 21-year old male patient had received more than 100 blood transfusions. In both patients, blood ferritin levels were as high as 5,584 and 9,665 g/litre respectively. Among the remaining 10 patients, 9 had biochemical signs of iron overload, such as high serum iron levels, reduced total siderophilin saturation capacity and blood ferritin levels of about 1,500 g/litre. Hepatic histology could be obtained from 5 patients and showed significant iron overload with cirrhosis in one case and clear-cut portal fibrosis in 3 cases. In all but the patient with multiple transfusions the iron overload was unrelated to transfusions, being present in their absence, usually during the 3rd and 4th decades of their life. The finding of iron overload requires preventive measures such as limitation of transfusions and elimination of iron by deferoxamine therapy.
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PMID:[Iron overload in congenital hemolytic anemia caused by pyruvate kinase deficiency. A major late complication]. 214 11

The etiology of many forms of liver disease is largely unknown. Recent research has identified certain immunogenetic factors which may play a role in the progression of alcoholic cirrhosis as well as autoimmune forms of cirrhosis. In this study we examined the role of familial alcoholism and HLA status in determining age of liver disease onset. Patients with biopsy-proven nonalcoholic autoimmune cirrhosis and having a history of familial alcoholism experience an earlier age of onset of liver disease than patients without a family history of alcoholism. The same result was true for patients with alcoholic liver disease. This effect may be more prominent in females. Subjects with HLA B-8 also had a younger age of onset of nonalcoholic autoimmune liver disease. The presence of a family history of alcoholism in conjunction with the presence of HLA B-8 and DR-3 also was related to an earlier age of disease onset. These findings suggest that the susceptibility to develop alcoholism and nonalcoholic autoimmune liver disease may be transmitted conjointly and point to potential fruitful areas of research for identifying individuals at risk for developing cirrhosis as well as detecting genetic markers for alcoholism.
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PMID:Early onset of nonalcoholic cirrhosis in patients with familial alcoholism. 217 63

Interferon-alpha (IFN-alpha) has been reported to be beneficial in the treatment of chronic active hepatitis occurring as a result of hepatitis B virus (HBV) infection. Treatment with IFN-alpha has been proposed as a means of reducing the high rate of allograft infection in clinical liver transplantation in patients transplanted for HBV-related chronic active hepatitis and cirrhosis who are positive for hepatitis B surface antigen (HBsAg). We obtained resected whole livers from two groups of patients who received liver transplants. Group A consisted of 11 patients who were HBsAg+ but were not treated with IFN-alpha, and group B consisted of 10 patients who were also HBsAg+ but received IFN-alpha therapy for 29.4 +/- 5.6 days prior to orthotopic liver transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. The liver tissue was stained with monoclonal antibodies to cell surface antigens unique to different mononuclear cell populations by the avidin-biotin-immunoperoxidase technique to determine the effect of IFN-alpha on the lymphocyte subsets as well as HLA antigen expression on liver-infiltrating mononuclear cells. The number of HLA-DR+ lymphocytes in the liver was significantly increased (P less than 0.005) within the portal areas in group B compared with that found in group A (84 +/- 14 versus 33 +/- 5 per one high-power field). Moreover, the intensity of the HLA-DR antigen expression on lymphocytes in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in group B than in group A. The number of natural killer (NK) cells was increased in the portal areas (P less than 0.05) of group B compared with group A. These alterations in the lymphocyte and NK cell populations present in the liver in response to IFN-alpha therapy presumably reflect an IFN-alpha-induced enhancement of the immune response to virus-infected cells.
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PMID:The effect of recombinant interferon-alpha on lymphocyte subpopulations and HLA-DR expression on liver tissue of HBV-positive individuals. 224 14

A 9-yr-old white girl with acute monoblastic leukemia received an HLA-identical, mixed lymphocyte culture-nonreactive bone marrow transplant from her sister. Twelve days after the transplant, a diffuse, pruritic, maculopapular rash involving the entire body surface (including the palms and soles) developed. Subsequent skin biopsy was consistent with cutaneous graft-versus-host disease, and biopsy-proven hepatic involvement manifested by severe, unremitting cholestatic jaundice soon followed. The patient's biliary status as monitored by serial liver biopsies demonstrated progression from chronic graft-versus-host disease to cirrhosis, culminating in death secondary to liver failure 25 mo after transplant.
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PMID:Secondary biliary cirrhosis as a consequence of graft-versus-host disease. 229 82

To assess the clinical and prognostic implications of human leukocyte antigen B8 in corticosteroid-treated severe autoimmune chronic active hepatitis, 81 consecutive patients were tested for histocompatibility antigens on the A and B loci, treated with corticosteroids, and followed prospectively for 111 +/- 8 mo. The 47 patients with HLA-B8 were younger (38 +/- 2 yr vs. 48 +/- 2 yr; p less than 0.01), had higher serum levels of aspartate aminotransferase (658 +/- 60 U/L vs. 465 +/- 49 U/L; p = 0.02) and bilirubin (7 +/- 1 mg/dl vs. 2.8 +/- 0.4 mg/dl; p = 0.003), and more commonly had histologic features of bridging necrosis, multilobular necrosis, and cirrhosis (85% vs. 56%; p less than 0.01) at presentation than the 34 patients without HLA-B8. Remission (79% vs. 71%), relapse after drug withdrawal (76% vs. 71%), treatment failure (13% vs. 6%), progression to cirrhosis (46% vs. 32%), and death from liver failure (6% vs. 3%) occurred as frequently in patients with and without HLA-B8. Importantly, HLA-B8-negative patients with HLA-A1 relapsed less frequently than HLA-B8-positive patients with and without HLA-A1- and HLA-B8-negative counterparts without HLA-A1. It is concluded that HLA-B8-positive patients are younger and have more severe disease at presentation than HLA-B8-negative patients. The HLA-B8 phenotype does not influence the response to corticosteroid therapy. HLA-B8-negative patients with HLA-A1 relapse less frequently than other phenotypes.
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PMID:Clinical and prognostic implications of HLA B8 in corticosteroid-treated severe autoimmune chronic active hepatitis. 233 97


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