1/44. panniculitis revealing qualitative alpha 1 antitrypsine deficiency (MS variant).A 16-year-old girl presented painful, red, nodular lesions on the abdomen. A cutaneous biopsy showed inflammatory cell infiltrate and fibrosis in the dermis and in the septa with isolated adipocyte lobules. alpha1-antitrypsin level was found to be normal but M1S phenotype of alpha1-antitrypsin was determined by isoelectric focusing in polyacrylamide gel. alpha1-antitrypsin level was normal for her family but M2S phenotype was found in her father. Alpha 1-antitrypsin (alpha1 AT) deficiency is a common hereditary disorder of Caucasians. The locus is pleiomorphic and 75 alleles have been identified. Numerous pathological mutations can be classified by the mechanisms which cause the deficiency. The major clinical importance of this deficiency is emphysema and liver disease. panniculitis is rarely reported and seems to occur principally for the ZZ or MZ phenotype and for low levels of alpha1 AT. MS phenotype has been more rarely reported and triggering agents such as trauma and infections must be present. However, normal levels of alpha1 AT in the serum have previously been reported as in our case, and we suggest the study of alpha1 AT phenotype even if the plasma level is normal.- - - - - - - - - - ranking = 1keywords = liver disease (Clic here for more details about this article) |
2/44. liver transplantation in alpha(1)-antitrypsin deficiency.Only a minority of infants born with alpha(1)-antitrypsin deficiency will develop serious liver disease during childhood, mostly but not always after neonatal cholestasis. Early prognosis is difficult and all children have to be followed up carefully. The liver disease progresses with varying speed and it lacks specific features. At the time of liver transplantation the young patients have no pulmonary disease induced by the deficiency and in those with renal involvement, the kidney problems can mostly be dealt with by conservative therapy. The peri- and postoperative care of the patients who undergo liver transplantation does not differ from the usual routines.- - - - - - - - - - ranking = 2keywords = liver disease (Clic here for more details about this article) |
3/44. Objective ranking of fibrosis in standard histologic sections of human neonatal liver: applicability to alpha1-antitrypsin deficiency.BACKGROUND: The etiologic heterogeneity of fibrotic liver disease has resulted in the formulation of diverse, often disease-specific, classification systems for biopsy assessment, based on tissue morphology and staining. Their qualitative nature and observer dependency remain a concern, and no classification exists for several significant conditions--for example, alpha1-antitrypsin deficiency (alpha1-ATD). The authors propose a disease- and morphology-independent numeric ranking system to objectively quantify fibrosis in a standard histologic section, based on its content of protein amino acids. This PNC system is applied to two cases of alpha1-ATD liver fibrosis. methods: High-performance liquid chromatography separation of the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC)-labeled acid hydrolysate of an individual needle biopsy section, followed by the calculation of specific amino acid ratios to eliminate confounding variables. RESULTS: As required by the PNC system, three numeric values were identified per tissue section, one increasing (P quotient), one decreasing (N quotient), one constant (C quotient) as fibrosis progresses, assessed by calibration against Knodell-staged samples. Generated for the alpha1-ATD sections, these three coordinates numerically referenced the degree of fibrosis in a manner that in each case was consistent with the histologic evaluation, the laboratory values, and the clinical course. CONCLUSIONS: Numeric, objective referencing of the degree of fibrosis in routine liver biopsy sections, based on the PNC system, is technically possible.- - - - - - - - - - ranking = 1keywords = liver disease (Clic here for more details about this article) |
4/44. alpha1-Antitrypsin deficiency and liver disease in children.This report describes the clinical, biochemical, and hepatic morphologic findings in ten children with severe serum alpha1-antitrypsin deficiency. Genetic protease inhibitor (Pi) phenotyping, using acid-starch gel and crossed antigen-antibody electrophoresis, demonstrated Pi phenotype ZZ in all our cases. In eight patients, manifestations of liver disease appeared during the first year of life. The case reports show that alpha1-antitrypsin deficiency should be suspected in any child with neonatal hepatitis, unexplained hepatomegaly or splenomegaly, or cirrhosis. In our report, one infant is normal at age 6 months, and one infant had progressive hepatic damage that culminated in liver failure and death at age 6 months. The variable clinical course and prognosis for infants with severe alpha1-antitrypsin deficiency is well illustrated by these two infants.- - - - - - - - - - ranking = 5keywords = liver disease (Clic here for more details about this article) |
5/44. Alpha-1-antitrypsin deficiency and liver in adults.Thirteen adult patients (aged 16 to 73 years) form 12 families are described with liver disease and alpha- 1- antitrypsin deficiency. Long-term observation of several of these patients suggests that the liver disease may be only slowly progressive, but review of possible factors aggravating this has failed to reveal any obvious clues. Progression to death from hepatic failure was the commonest outcome, but one patient developed a malignant hepatoma and two others died because of intraperitoneal haemorrhage due to ruptured cirrhotic nodules--a complication not hitherto described in association with this condtion. diagnosis of alpha-1-antitrypsin deficiency was based on serological, histological, immunopathological and genetic studies. The most useful screening test in liver disease was found to be the demonstration of PAS positive globules in liver biopsy material which is diagn by immunofluoresence or immunoperoxidase, the latter being a superior technique. serum estimation of alpha-1 -antitrypsin deficiency was performed by immunoelectropharetic and immunodiffusion techniques, the former being preferred because it gave more consistent results. Both methods, however, were of limited value since wide variations in the serum values are commonly found in normal and abnormal states. Genotyping was carried out using starch gel electrophoresis and although of value in family studies, its value as a diagnositc aid is limited because of technical difficulties and also because alpha-1-antitrypsin accumulation in the liver may be found in both homozygous and heterozygous states. It is suggested that adult liver disease associated with abnormalities in alpha-1-antitrypsin may be more common than has hitherto been reported. This condition should be systematically sought in all cases of liver disease of uncertain aetiology.- - - - - - - - - - ranking = 5keywords = liver disease (Clic here for more details about this article) |
6/44. alpha 1-antitrypsin deficiency and infantile liver disease.Infantile liver disease with deficiency of serum alpha1-antitrypsin is illustrated by a description of the clinical, biochemical, and pathological findings in two affected families. The simplicity of the diagnostic tests is emphasized. review of 61 biopsies of liver from children and adolescents provided a further 3 cases. It is prudent to exclude this metabolic defect in children with a history of "neonatal hepatitis".- - - - - - - - - - ranking = 5keywords = liver disease (Clic here for more details about this article) |
7/44. Immunological changes and liver disease associated with alpha1-antitrypsin deficiency.A female aged 60 years with heterozygous alpha-1-antitrypsin deficiency developed a progressive and ultimately fatal liver disease with the clinical, biochemical, immunological and histological characteristics of active chronic hepatitis. It is suggested that the hepatic disease of A-AT deficiency be included among the types of liver disease which may initiate a progressive immunopathic response.- - - - - - - - - - ranking = 6keywords = liver disease (Clic here for more details about this article) |
8/44. Combined liver-kidney transplantation in a 15-year-old boy with alpha1-antitrypsin deficiency.Alpha1-antitrypsin (1-AT) deficiency is the most common genetic cause of liver disease in infants and children. The major clinical manifestations include liver disease (primarily in children) and emphysema in adults. For patients who progress to cirrhosis and liver failure, liver transplantation provides a metabolic cure for the deficiency and presumably prevents the associated complications. Several case reports in the pediatric literature describe glomerulonephritis in the setting of severe 1-AT deficiency, but this association is less well documented in adults. End-stage chronic kidney disease is a rare finding in the literature and kidney transplantation is the treatment of choice. We report on a 15-year-old boy with 1-AT deficiency and consequent end-stage liver disease and membranoproliferative glomerulonephritis rapidly progressing to renal failure, who successfully underwent combined liver-kidney transplantation.- - - - - - - - - - ranking = 2keywords = liver disease (Clic here for more details about this article) |
9/44. role of alpha-1-antichymotrypsin deficiency in promoting cirrhosis in two siblings with heterozygous alpha-1-antitrypsin deficiency phenotype SZ.BACKGROUND: Alpha-1-antitrypsin (A1AT) deficiency is the most common inherited metabolic disorder with the potential to cause injury in the lung and liver. Recent reports suggested that alpha-1-antichymotrypsin (A1AC) deficiency may also be a possible cause of chronic liver disease. However, it has received little attention and is rarely investigated in the clinical setting. AIMS: To assess the role of A1AC deficiency in the pathogenesis of chronic liver disease in two siblings with heterozygous A1AT phenotype Pi SZ. patients: Two adult siblings with an A1AT Pi SZ phenotype and reduced levels of A1AC consistent with heterozygosity who developed cirrhosis and underwent liver transplantation. methods AND RESULTS: A1AT and A1AC levels in plasma measured by electroimmunoassay were 74 mg/dl and 90 mg/dl (140-470) and 0.12 mg/ml and 0.14 mg/ml (0.173-0.46), respectively. immunohistochemistry revealed an apparent accumulation of both A1AT and A1AC in hepatocytes. A previously reported point mutation in exon III (Pro(229) to Ala substitution) of the A1AC gene was not detected by polymerase chain reaction amplification and a single strand conformation polymorphism analysis. CONCLUSIONS: Our report represents the first case of two siblings with A1CA phenotype Pi SZ who developed cirrhosis and underwent liver transplantation. Both siblings were heterozygous for A1AT and A1AC deficiency suggesting that combined deficiency of these two major serine protease inhibitors may enhance the risk of developing liver disease.- - - - - - - - - - ranking = 3keywords = liver disease (Clic here for more details about this article) |
10/44. A patient with autoimmune hepatitis type I, Addison's disease, atrophic thyroiditis, atrophic gastritis, exocrine pancreatic insufficiency, and heterozygous alpha1-antitrypsin deficiency.This report describes a 60-yr-old white male presenting with decompensated liver cirrhosis. He had a history of Addison's disease for 36 yr, primary hypothyroidism for 5 yr, and moderate alcohol consumption. His laboratory studies and a liver biopsy supported the diagnosis of autoimmune hepatitis. Furthermore, he was found to be heterozygous for the piZ allele of the alpha1-antitrypsin gene with normal serum alpha1-antitrypsin levels and absence of pulmonary affection. Mucosal biopsies revealed moderately severe atrophic gastritis; however, signs of pernicious anemia were missing. An association of autoimmune hepatitis with endocrine disorders and atrophic gastritis has been described. Long term hydrocortisone therapy for his adrenal insufficiency may have prevented a faster course of the liver disease, whereas the heterozygous alpha1-antitrypsin deficiency and moderate alcohol consumption constituted additional risk factors ultimately leading to the development of cirrhosis.- - - - - - - - - - ranking = 1keywords = liver disease (Clic here for more details about this article) |
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