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

Two unreleated adult males were found to be suffering from an association of pan-lobular severe emphysema and hepatomegally of unknown origin which led to the discovery of a marked deficit in alpha-1 antitrypsin (A1-AT) in relation to a PiZ phenotype. Liver biopsy revealed cirrhosis with portal fibrosis in one case and in both cases fatty infiltration with the accumulation of a glycoprotein antigenically identical to A1-AT. Electron microscopy showed this protein to be situated within the dilated lumina of the endoplasmic reticulum of the hepatocytes. A1-AT deficiency is usually associated with pulmonary involvement only in the adult and liver involvement only in the child. The association of the two remains rare--hence the interest of the two cases reported.
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PMID:[Pulmonary emphysema and hepatic involvement by alpha-1 antitrypsin deficiency in two adults with a PiZ phenotype (author's transl)]. 30 25

Hepatic cirrhosis secondary to deficit of alpha-1 antitrypsin is an entity rarely observed among the adult population. We describe the clinical and histological characteristics of a patient with PiZZ phenotype, affected by an hepatic cirrhosis of this etiology, as well as the analytical and phenotypical study of his close relatives, all of which presented a type-Z mutation.
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PMID:[Hepatic cirrhosis and alpha 1-antitrypsin deficit: a family study]. 142 Jul 61

A 34 year old woman admitted to the department of Gastroenterology of Florence hospital was diagnosed as suffering from liver cirrhosis with an alpha-1 antitrypsin deficiency (PiZZ phenotype). Liver biopsy showed the presence of intra-hepatocyte PAS-positive inclusions and the presence of alpha-1 antitrypsin was confirmed using the immunoperoxidase technique. No other organ appeared to be affected and respiratory function tests were within normal limits. The quantitative assay of alpha-1 antitrypsin was higher than values reported in the literature for PiZZ homozygotes. The authors report the case and discuss some aspects of this disease.
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PMID:Cirrhosis associated with homozygous alpha-1 antitrypsin deficiency in the adult: a case report. 175 19

A newly-born male affected by extrahepatic biliary atresia with an alpha-1 antitrypsin pi ZZ deficiency is presented. Parents, Pi MZ, showing no signs of affection either in liver or lungs. His two brothers and one sister died at nine months, 7 years and 22 months respectively. Two brothers showed cirrhosis of the liver, the sister showed extrahepatic biliary atresia, and in all three patients there was an alpha-1 antitrypsin deficiency. Authors want to emphasize the presence of extra-hepatic biliary atresia in both brother and sister who had also an alpha-1 antitrypsin deficiency because this is an infrequent association which requires different treatment.
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PMID:[Alpha 1-antitrypsin deficiency and atresia of the bile ducts]. 349 22

Alpha-1-antitrypsin deficiency has long been known to cause liver cirrhosis in man, but whether it does so in the dog is uncertain. To investigate this point 57 dogs with clinically and histopathologically diagnosed chronic liver disease were examined. Isoelectric focusing of blood serum from these dogs and from 25 clinically healthy dogs revealed three different types of alpha-1 antitrypsin, designated F(fast), I(intermediate) and S(slow). They appeared in both homozygous and heterozygous forms, the F type being seen most frequently. The I type was more common in cocker spaniels than in other breeds. Immunostaining for alpha-1 antitrypsin revealed that 37 diseased dogs had alpha-1 antitrypsin in the cytoplasm of their hepatocytes. Of these, 21 dogs had globular alpha-1 antitrypsin inclusions in the endoplasmic reticulum, indicating aggregated protein. Accumulated alpha-1 antitrypsin was found most frequently in dogs having the I and S types of alpha-1 antitrypsin, either homozygously or heterozygously. With a few exceptions, F-homozygotic dogs had no hepatocellular alpha-1 antitrypsin accumulation. As alpha-1 antitrypsin aggregation is lethal to hepatocytes and as cell death attracts mononuclear blood cells whose cytokines induce continued alpha-1 antitrypsin synthesis with subsequent risk of further alpha-1 antitrypsin accumulation, liver disease may thus be maintained. Whether alpha-1 antitrypsin aggregates actually initiate liver disease in dogs, as in man, remains to be elucidated by further biochemical investigation of the three canine alpha-1 antitrypsin types found.
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PMID:Hepatic accumulation of alpha-1-antitrypsin in chronic liver disease in the dog. 788 57

End-stage liver disease secondary to cryptogenic cirrhosis is the indication for orthotopic liver transplantation (OLT) in 7% to 14% of recipients. However, there are no reports documenting the outcome of OLT for this indication. The aim of this study was to determine (1) survival and (2) the incidence of histological recurrence of cryptogenic cirrhosis after OLT. Between March 1985 and December 1994, 560 OLTs were performed at our institution. Of these, 39 transplants for cryptogenic cirrhosis were in patients who met the following criteria: antinuclear antibody < 1:40; negative anti-smooth muscle antibody, antimitochondrial antibody, polymerase chain reaction for hepatitis C virus, and hepatitis B surface antigen results; normal ceruloplasmin and alpha-1 antitrypsin phenotype; transferrin saturation < 65%; and liver biopsy specimen not suggestive of hemochromatosis or other known disorders. Histological recurrence was assessed with protocol liver biopsies in all patients who survived longer than 6 months. The mean age of cryptogenic recipients at the time of transplantation was significantly lower (40.6 years; range, 3 to 63 years) than that of noncryptogenic recipients (48.5 years; range, 1-70; P < .03). Median modified Child's-Pugh score was slightly higher for cryptogenic recipients at the time of transplantation (10.0 + 0.08 standard error of mean [SEM]), than for the noncryptogenic recipients (9.0 + 0.03 SEM; P < .02). Actuarial survival was 72% (+ 0.07 SEM) at 1 and 58% (+ 0.08 SEM) at 5 years for cryptogenic recipients compared with 89% at 1 and 80% at 5 years for noncryptogenic recipients. The difference in survival was significant (P < .001) at both 1 and 5 years. Among the 27 cryptogenic recipients surviving more than 6 months (mean follow-up, 5.5 years), 6 have persistent hepatitis histologically without apparent infectious, vascular, biliary, or drug origins. Four patients (15%) had chronic active hepatitis, and 2 (7%) had steatohepatitis. No cases of recurrent cryptogenic cirrhosis were seen. OLT for cryptogenic cirrhosis is associated with a poor outcome compared with other indications, hepatitis of uncertain origin occurred in 22% of cryptogenic recipients surviving longer than 6 months, and no evidence of recurrence of cryptogenic cirrhosis was seen thus far in follow-up.
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PMID:Liver transplantation for cryptogenic cirrhosis. 934 64

Alpha-1 antitrypsin deficiency is an inherited disease affecting the lung and liver. The typical pulmonary manifestation is chronic obstructive pulmonary disease and emphysema. Severe chronic obstructive pulmonary disease may occur in young adulthood, and terminal respiratory insufficiency causes premature death in many patients. In the liver, alpha-1 antitrypsin deficiency may manifest as benign neonatal hepatitis syndrome; a small percentage of adults develop liver fibrosis, with progression to cirrhosis and hepatocellular carcinoma. The alpha-1 antitrypsin molecule is a serine protease inhibitor that is predominantly produced in the liver. Its most important physiologic functions are the protection of pulmonary tissue from aggressive proteolytic enzymes and regulation of pulmonary immune processes. Diagnosis of alpha-1 antitrypsin deficiency can be established by measurement of the serum alpha-1 antitrypsin concentration or by genetic analysis. Treatment is similar to the usual treatment for patients with chronic obstructive pulmonary disease. A further option is substitution therapy with human alpha-1 antitrypsin. The targets of treatment are the prevention of the accelerated decline of pulmonary function, reduction of lung infections, and improvements in exercise capacity.
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PMID:Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment. 1850 Dec 15

Protein-losing enteropathy (PLE) is a rare syndrome of gastrointestinal protein loss that may complicate a variety of diseases. The primary causes can be divided into erosive gastrointestinal disorders, nonerosive gastrointestinal disorders, and disorders involving increased central venous pressure or mesenteric lymphatic obstruction. The diagnosis of PLE should be considered in patients with hypoproteinemia after other causes, such as malnutrition, proteinuria, and impaired protein synthesis due to cirrhosis, have been excluded. The diagnosis of PLE is most commonly based on the determination of fecal alpha-1 antitrypsin clearance. Treatment of PLE targets the underlying disease but also includes dietary modification, supportive care, and maintenance of nutritional status. In this article, cases illustrating a variety of clinical presentations and etiologies of PLE are presented, and its diagnostic approach and treatment are reviewed.
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PMID:Protein-losing enteropathy: case illustrations and clinical review. 1978 26

Hereditary hemochromatosis and alpha-1antitrypsin deficiency are genetic diseases characterized by endoplasmic reticulum (ER) stress with subsequent development of liver disease. Our aim was to estimate the frequency of hemochromatosis gene (HFE) mutant alleles (C282Y and H63D) and alpha-1 antitrypsin S/Z variants among Egyptian HCV cirrhotic patients and in hepatocellular carcinoma patients and to evaluate their effects on disease progression. HFE and alpha-1 antitrypsin polymorphisms were characterized in 200 Egyptian patients with HCV infection (100 patients complicated with cirrhosis, 100 patients with HCC) and 100 healthy subjects who had no history of any malignancy. The frequencies of HD genotype of H63D mutation were significantly increased in HCC patients compared to control group and to cirrhosis group. Also, the frequencies of DD genotype were significantly increased In HCC group compared to control group and to cirrhosis group. Our results suggested that Carriers of the D allele of H63D mutation were significantly more likely to develop HCC.
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PMID:Polymorphisms of hemochromatosis, and alpha-1 antitrypsin genes in Egyptian HCV patients with and without hepatocellular carcinoma. 2192 77

Alpha-1 antitrypsin deficiency is a hereditary metabolic disorder predisposing its carrier to lung and liver damage. Organ damage results from decreased secretion of alpha-1 antitrypsin from hepatocytes to circulation, caused by a genetic mutation. Decreased alpha-1 antitrypsin level predisposes to early-onset pulmonary emphysema. Unsecreted alpha-1 antitrypsin accumulating into hepatocytes may in turn lead to an inflammatory reaction, increase in fibrous tissue and finally to liver cirrhosis.
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PMID:[Alpha-1 antitrypsin deficiency]. 2203 28


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