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)

The authors describe a method for combined measurements of the plasma trypsin-like proteinases, alpha 1-antitrypsin and alpha 2-macroglobulin. The values of these parameters' activities in the plasma of normal subjects and patients with peritonitis and liver cirrhosis are presented. The suggested method may be used for identification of the type of disorders in the system of trypsin-like proteinases and endogenous inhibitors in other diseases.
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PMID:[Use of a method of combined determination of the activity of the trypsin-like proteinases, alpha 1-antitrypsin and alpha 2-macroglobulin, in a gastroenterology clinic]. 169 55

Changes in the activities of blood protease inhibitors and acute-phase reactive substances during surgical resection of liver cirrhosis were investigated by measuring the pre- and postoperative blood concentrations of alpha 1-antitrypsin (alpha 1AT), alpha 2-macroglobulin (alpha 2MG), pancreatic secretory trypsin inhibitor (PSTI), urinary trypsin inhibitor (UTI) and C-reactive protein (CRP), in patients with liver cirrhosis who underwent hepatectomy (Group A, n = 19), those without liver cirrhosis who underwent hepatectomy (Group B, n = 6) and those without liver cirrhosis who underwent surgeries other than hepatectomy (Group C, n = 5). On examining the preoperative blood levels of protease inhibitors, Group A had an increased level of alpha 2MG and a decreased level of UTI compared to Groups B and C. alpha 1AT and CRP began to increase on the first day following hepatectomy and formed peaks on the third postoperative day. The increases were significantly higher in Group B than Group A (p less than 0.01). To investigate factors causative of these differences, alpha 1AT and CRP on the third postoperative day were compared in relation to the time of operation, amount of intraoperative bleeding, weight of the resected liver and preoperative ICGR15. alpha 1AT and CRP were significantly correlated to only preoperative ICGR15. PSTI was increased postoperatively but showed no difference between Groups A and B.
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PMID:[Postoperative change of serum protease inhibitor and C-reactive protein level--with special reference to surgical resection of liver cirrhosis]. 171 15

The alpha 1-antitrypsin deficient subject (protease inhibitor (PI) phenotype ZZ) has an increased susceptibility to liver disease. The condition is most commonly identified in early infancy as a conjugated hyperbilirubinaemia with hepatitis (11%) or a bleeding state due to vitamin K malabsorption (2%). 50% of cases have cirrhosis and 25% die in the first decade of life. A further 2% present with cirrhosis in later childhood. Adult males are at risk of hepatoma development with or without cirrhosis. Diagnosis is by isoelectric focussing or allele-specific oligonucleotide hybridization. The treatment is that of cholestasis and cirrhosis including transplantation. The pathobiology of the deficiency state, the mechanism of liver damage and the vulnerability of the newborn liver are discussed in this review. A plea is made for a trial of infusions of alpha 1-antitrypsin in early infancy, as is used safely but without proven efficacy in the emphysematous PIZZ subject. Prospects of therapy by gene modification are also reviewed.
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PMID:Alpha 1-antitrypsin deficiency and liver disease: clinical presentation, diagnosis and treatment. 174 15

In 31 children with congenital alpha 1-antitrypsin deficiency the concentration of procollagen type III peptide was determined in a trial establishing liver fibrosis degree and monitoring of fibrosis progression. No correlation was found between the degree liver fibrosis determined by histological examination and the serum concentration of procollagen type III peptide. The concentration of procollagen type III peptide was higher with coexistent cholestasis and in case of inflammatory processes outside the liver (pneumonia). In progressing cirrhosis with inflammatory reaction the concentration was higher than in advanced cirrhosis and non-inflammatory liver fibrosis.
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PMID:Procollagen type III peptide in the assessment of liver fibrosis in children with congenital alpha-1-antitrypsin deficiency. 184 33

alpha 1-Antichymotrypsin (ACT) and alpha 1-antitrypsin (AAT) are two closely related antineutrophil proteinase inhibitors. Whereas AAT deficiency is clearly linked to liver disease, an association between liver disease and partial ACT deficiency has not been established. In a previous study we noted an increased prevalence of liver abnormalities among subjects with heterozygous ACT deficiency. To study a possible association between partial ACT deficiency and liver disease, we screened 316 consecutive patients with biopsy-verified liver disease for partial ACT deficiency and compared the prevalence with that of an unselected adult population in a case-control study. In all, 9 of 316 patients had partial ACT deficiency, which is more than expected (prevalence ratio (PR), 2.46 (1.15-5.27), P less than 0.05). The prevalence of partial ACT deficiency was highest in the chronic active hepatitis (5 of 40; PR, 12.0 (5.33-27.0] and the cryptogenic cirrhosis (3 of 24; PR, 12.0 (4.38-32.9] subgroups. In the chronic active hepatitis subgroup two patients (PR, 8.16 (2.25-29.5] were ACT deficiency heterozygotes, thus partly explaining the high prevalence of partial ACT deficiency among patients with chronic liver disease. The majority (6 of 9) of the patients with partial ACT deficiency lacked autoimmune and viral markers and were thus cryptogenic. The present findings show that partial ACT deficiency and chronic cryptogenic liver disease are associated. To some extent (the true magnitude of which is at present unknown) partial ACT deficiency is caused by a rare trait, heterozygous ACT deficiency, which in parallel with heterozygous alpha 1-antitrypsin deficiency (PiMZ) also seems to be associated with chronic cryptogenic liver disease.
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PMID:Partial deficiency of alpha 1-antichymotrypsin is associated with chronic cryptogenic liver disease. 187 43

Ascitic fluid alpha 1-antitrypsin (AF-AAT) was compared with ascitic fluid total protein (AF-TP) and the serum-ascites albumin gradient (SAAG) in the differential diagnosis of ascites. The study included 82 consecutive patients of which 42 had cirrhosis, 8 hepatoma (with cirrhosis), and 27 malignant ascites (peritoneal 18, liver 9). The concentration of AF-AAT (milligrams per deciliter) was significantly elevated (P less than 0.001) in hepatoma (174 +/- 123), malignant liver disease (232 +/- 119) and peritoneal neoplasms (376 +/- 106) in comparison with cirrhotics (66 +/- 33). In separating ascites caused by cirrhosis or malignancy, AF-AAT (discriminating limit of 120 mg/dl) had a 96% sensitivity, 95% specificity, and 96% diagnostic efficacy, which was superior to the 87% observed for AF-TP and 86% for the SAAG. Similar results were obtained for the A/S AAT ratio but this test was not available in all patients. AF-AAT was particularly useful in patients with malignancy causing portal hypertension as assessed by SAAG (hepatoma, malignant liver disease). We conclude that AF-AAT may be a valuable parameter in the differential diagnosis of ascites.
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PMID:Ascitic fluid alpha 1-antitrypsin. 216 27

In the United States, a large percentage of patients with hepatocellular carcinoma are serologically negative for hepatitis B. We conducted a retrospective study to determine the prevalence of hepatitis C antibody in the sera of 59 patients with hepatocellular carcinoma who were HBsAg-negative and had no evidence of alcoholic liver disease, primary biliary cirrhosis, autoimmune hepatitis, hemochromatosis or alpha 1-antitrypsin deficiency. Twenty patients (34%) were hepatitis C antibody-positive and hepatitis B core antibody-negative. All twenty patients had underlying cirrhosis, and seven (35%) had histories of transfusions. Eleven (19%) additional patients were also hepatitis C antibody-positive but were hepatitis B core antibody-positive as well. Twenty-one (36%) patients were both hepatitis C antibody- and hepatitis B core antibody-negative and seven (12%) were hepatitis C antibody-negative but hepatitis B core antibody-positive. The prevalence of hepatitis C antibody was also determined among three other population groups serving as controls and found to be 14% in 28 HbsAg-positive patients with hepatocellular carcinoma, 44% in 76 patients with cryptogenic cirrhosis and 0.5% in 200 consecutive volunteer blood donors. We conclude that hepatitis C antibody is prevalent among patients with hepatocellular carcinoma and may therefore be a common causative agent of this disease. A significant number of patients with and without cirrhosis, negative for hepatitis C antibody and hepatitis B core antibody, remain without a discernible cause for this malignancy. Perhaps a second- or third-generation test will detect hepatitis C antibody in some of these patients.
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PMID:Hepatitis C-associated hepatocellular carcinoma. 165 57

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)
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PMID:Genetics of alpha 1-antitrypsin deficiency in relation to neonatal liver disease. 218 61

We have studied the clinical histories and liver biopsy findings in 1951 consecutive adult patients with suspected chronic liver disease, and in four known PiZ-homozygous alpha 1-antitrypsin-deficient patients with emphysema (candidates for lung transplant) and no known liver disease, in order to assess the importance of periportal alpha 1-antitrypsin granules in the liver and their possible causal role in liver disease, and to assess the value of possible screening tests. Periportal granules were found in 30 (1.5 per cent) of the 1951 liver biopsies and in all four known PiZ-homozygous subjects. They were the sole putative aetiological agent in eight of 85 patients (9.4 per cent) with otherwise cryptogenic cirrhosis and present in 2.5 per cent of patients with cirrhosis of known aetiology (alcohol, autoimmune etc.). All but one were Z phenotype (seven homozygotes, 22 heterozygotes). alpha 1-Antitrypsin granules were seen in 12 patients (including three of four lung transplant candidates) with no histological chronic liver disease. Determination of serum alpha 1-antitrypsin levels was quite unhelpful in identifying these patients. This study does not support the concept that periportal alpha 1-antitrypsin granules are necessarily pathogenic, but in some cases they may be causally related to otherwise cryptogenic liver disease. The presence of granules gave no important diagnostic, therapeutic or prognostic information.
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PMID:Alpha 1-antitrypsin granules in the liver--always important? 221 74

On the basis of cooperation with the Children's Health Centre the role was analysed of certain phenotypes of alpha 1-antitrypsin (alpha 1-AT), mainly Pi Z and Pi MZ phenotypes in the development of infantile cirrhosis. A significant participation was demonstrated of the latter phenotype in patients developing infantile cirrhosis. The preliminary analysis of the incidence of pathological alpha 1-AT phenotypes in the group of patients with cirrhosis manifested at the adult age seems to indicate the higher incidence of the Pi MZ phenotype as compared with the general population. The genetically determined low serum alpha 1-AT activity is probably one out of many factors determining the development of this disease. Further studies will be aimed at explaining whether the combination of action of two factors: alpha 1-AT deficiency and exposure to hepatotoxic agents is not accelerating the appearance of the disease and is not potentiating its clinical intensity.
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PMID:[Alpha 1-antitrypsin phenotypes and their role in the development of early and late cirrhosis of the liver]. 226 Mar 9


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