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)

Alpha-1-antitrypsin deficiency is a common autosomal recessive disorder associated with premature development of emphysema, liver cirrhosis and hepatocellular carcinoma. This article reviews the existing literature on alpha-1-antitrypsin deficiency, with an emphasis on recent developments. A description of the protein, gene structure and function of alpha-1-antitrypsin as well as clinical aspects are presented. Treatment issues are addressed and a framework for the diagnostic workup and management of patients with alpha-1-antitrypsin deficiency and chronic liver disease is provided.
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PMID:Alpha-1-antitrypsin deficiency and liver disease. 798 61

Genetically determined deficiency of alpha-1-antitrypsin, the primary serum protease inhibitor, can result in pulmonary emphysema or liver cirrhosis, and panniculitis may be an early symptom. A case of recurring panniculitis in a 29 year-old woman is described, which led to the diagnosis of severe alpha-1-antitrypsin deficiency (Pi ZZ). Serum alpha-1-antitrypsin levels should be measured in patients presenting with panniculitis.
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PMID:[Panniculitis associated with severe alpha 1-antitrypsin deficiency]. 801 35

1. The Z deficiency variant of alpha 1-antitrypsin predisposes the homozygote to early-onset panlobular emphysema and results in the accumulation of antitrypsin within the hepatocyte, which leads to hepatocellular damage and cirrhosis. The mechanism of this accumulation has been shown to be due to the Z mutation (Glu-342-->Lys) perturbing the structure of the protein, allowing a unique interaction between the reactive-centre loop of one molecule and the A sheet of a second. This loop-sheet polymerization occurs spontaneously at 37 degrees C in purified plasma Z but not M antitrypsin. The rate of polymerization is greatly accelerated at 41 degrees C and is blocked by the insertion of a specific peptide into the A sheet of the antitrypsin molecule. Electron microscopy and circular dichroic spectral analysis confirm that the Z antitrypsin polymers formed in vitro have structural identity with those isolated from the liver of a Z homozygote. 2. That loop-sheet polymerization is a more general phenomenon was shown by the examination of a second deficiency variant, antitrypsin Siiyama (Ser-53-->Phe), which is also associated with liver inclusions. Electron microscopy confirmed that isolated antitrypsin Siiyama from the plasma of a homozygote was present as long chains of polymers identical with those of Z antitrypsin.
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PMID:Loop-sheet polymerization: the structural basis of Z alpha 1-antitrypsin accumulation in the liver. 803 2

A 53-year-old man with alpha-1-antitrypsin deficiency had an 8-year history of progressive dyspnoea and two episodes of bleeding oesophageal varices with liver decompensation. After the diagnosis of terminal pulmonary emphysema (Fig. 1) and liver cirrhosis with progressive liver failure was made, he was accepted for combined lung and liver transplantation. METHODS. Anaesthesia was induced with thiopentone and fentanyl and maintained with fentanyl, midazolam, and isoflurane. After relaxation with succinylcholine, the patient's trachea was intubated with a left endobronchial double-lumen tube. Haemodynamic monitoring included arterial, central-venous, pulmonary-artery, and capillary-wedge pressures and cardiac output measurement. Ventilatory monitoring consisted of pulse oximetry, side-stream spirometry, and continuous measurement of arterial and mixed-venous blood oxygen saturation with fibreoptic catheters. A left single-lung transplantation was performed under one-lung ventilation without cardiopulmonary bypass. Prostacyclin was infused to reduce pulmonary vascular resistance. The transplant was ventilated separately with 50% oxygen and positive end-expiratory pressure of 8-10 cm H2O, and then liver transplantation was carried out. The institution of veno-venous bypass during the anhepatic phase failed because of portal-vein and axillary-vein thrombi. RESULTS. Total operation time was 6 h 30 min. Clamping of the left pulmonary artery lasted 45 min and the duration of the anhepatic phase was 92 min. Ventilation and oxygenation during lung transplantation caused no problems (Table 1). Clamping of the left pulmonary artery caused a slight increase in pulmonary vascular resistance (104 to 124 dyn.s.cm-5) and mean pulmonary artery pressure (25 to 27 mm Hg) without a decrease in cardiac index (Table 2). During the anhepatic phase with exclusion of the portal vein and inferior vena cava, a marked decrease in cardiac index (-27.2%) was seen (Table 4). The operation required substitution with 10 units packed red blood cells, 12 units fresh frozen plasma, and 5 platelet concentrates. The post-operative course showed normal liver graft function (Table 5). Acute pulmonary rejection on the 7th day was treated successfully with methylprednisolone. The patient's trachea has extubated 10 days after transplantation and he was discharged from the intensive care unit 2 weeks later. CONCLUSION. The management of this combined lung and liver transplantation was performed according to the experience with isolated lung and liver transplants in our hospital. Aggressive haemodynamic and ventilatory monitoring, including systemic and pulmonary arterial fibreoptic catheters, seems of particular importance in such high-risk procedures.
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PMID:[Combined lung and liver transplantation. Anesthesiologic management]. 804 61

There are genetic and exogenous factors responsible for alpha 1-antitrypsin (alpha 1-AT) deficiency which may lead to cirrhosis of the liver and emphysema. The present study was initiated on a biochemical level in order to determine whether acetaldehyde, the major product of ethanol metabolism, is capable of influencing the physiological effect of alpha 1-AT upon elastase, an enzyme which is capable of inducing emphysema. The effects of acetaldehyde and ethanol upon elastase and alpha 1-AT were tested. Acetaldehyde at 0.3-M and 1.2-M concentrations inhibited the anti-elastase activity of alpha 1-AT. Acetaldehyde at 0.03-M and 0.07-M concentrations did not affect elastase activity and had a slight effect at 0.12-M levels. Equivalent amounts of ethanol were without influence upon elastase activity or alpha 1-AT function. These data provide biochemical support for the possibility that heterozygous males with lower than normal alpha 1-AT levels may be at much higher risk to develop liver disease, emphysema, and alpha 1-AT deficiency as a consequence of chronic exposure to ethanol and concomitant circulating acetaldehyde levels.
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PMID:Acetaldehyde inhibits the anti-elastase activity of alpha 1-antitrypsin. 806 May 17

An association of alpha 1-antitrypsin deficiency with glomerulonephritis is rare and has so far been observed only in children or young adults. We report a 63-year-old man with severe alpha 1-antitrypsin deficiency associated with pulmonary emphysema, cirrhosis of the liver, and mesangioproliferative glomerulonephritis with nephrotic syndrome. Following initial presentation with nephropathy, further work-up revealed alpha 1-antitrypsin deficiency of proteinase inhibitor Z. In the absence of glomerular alpha 1-antitrypsin deposits the relationship between renal disease and alpha 1-antitrypsin deficiency remains unclear. alpha 1-Antitrypsin deficiency should be considered in adults with abnormal renal function and chronic liver disease.
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PMID:Glomerulonephritis as late manifestation of severe alpha 1-antitrypsin deficiency. 808 78

alpha 1-antitrypsin (alpha 1-AT) is a glycoprotein called an acute phase reactant, which increases in blood in a variety of inflammations. alpha 1-AT deficiency with an inherited remarkable reduction of alpha 1-AT in blood has two major disorders, pulmonary emphysema and liver diseases, particularly an infantile cirrhosis. It is of great interest that each disorder has peculiar mechanisms based on an imbalance between proteases and protease inhibitors. alpha 1-AT constitutes genetic polymorphism of which alpha 1-AT deficiency presents rare PiZ or PiZ-like variants. alpha 1-AT deficiency is an inherited metabolic disorder associated with not only a severe reduction of alpha 1-AT in blood, but also amino acid substitutions of alpha 1-AT due to gene variations.
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PMID:[Liver cirrhosis associated with alpha 1-antitrypsin deficiency]. 811 96

Alpha-1-antitrypsin (alpha-1-AT) deficiency can lead to juvenile liver cirrhosis and lung emphysema in adulthood. The deficiency Z allele is caused by a base transition. Temperature gradient gel electrophoresis (TGGE) and hybrid isoelectric focusing (HIEF) were used to detect carriers of the Z mutation of the alpha-1-AT gene. The resulting data were compared. To verify carriers at the sequence level, a manual nonradioactive sequencing strategy was established. Among our sample of carriers of the Z mutation, two were not detected by HIEF that could be identified by TGGE. DNA of all TGGE identified individuals harboring the Z mutation of the alpha-1-AT gene were sequenced nonradioactively. All carriers harbored a G to A transition at position 11.940. This mutation is described to cause the altered protein.
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PMID:TGGE and HIEF: a comparison of two methods in the detection of carriers of the Z mutation in the alpha-1-antitrypsin gene. 816 37

Alpha-1-antitrypsin deficiency is an inborn metabolism error which can cause emphysema and liver disease. As regards the pathophysiology of liver disease, this deficiency is poorly understood, and it is also not known why only a small proportion of Pi ZZ individuals progress towards cirrhosis and liver failure. Since there is no specific therapy for end-stage liver disease associated with alpha-1-antitrypsin deficiency, patients are considered candidates for liver transplantation. In this paper, the natural history of 16 children who underwent liver transplantation is reviewed. Fourteen patients had neonatal cholestasis as a first symptom of the disease and hepatosplenomegaly was present in all children by the age of 12 months. In 11 children, jaundice recurred, always with liver function deterioration. Two patients had a histological paucity of interlobular bile ducts and required early transplantation due to rapid progression of liver failure. At the time of pretransplant assessment, all the patients in this study had portal hypertension and seven of them had experienced at least one episode of gastrointestinal bleeding. One child had moderate intrapulmonary shunts with hypoxemia, but the others had normal spirometry and blood gases. There was no other extrahepatic complication of alpha-1-antitrypsin deficiency. Eighteen orthotopic liver transplantations were performed in 16 patients. One patient died 8 days after retransplantation due to graft necrosis. Fifteen patients (94%) were alive after a median follow-up of 22 months with an excellent quality of life, normal serum alpha-1-antitrypsin levels and without evidence of liver disease recurrence or pulmonary complications.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver transplantation for end-stage liver disease associated with alpha-1-antitrypsin deficiency in children: pretransplant natural history, timing and results of transplantation. 820 Dec 25

The weights of the individual carotid bodies and cardiac ventricles were obtained at necropsy in five series of subjects. The first comprised 10 cases free of cardiopulmonary disease to act as controls. The second consisted of 10 cases of pulmonary emphysema. The third was composed of 8 cases characterized by sustained alveolar hypoxia due to causes other than pulmonary emphysema. The fourth comprised 10 cases of systemic hypertension or severe left ventricular failure. The fifth was made up of 10 cases of diseases of the liver or alimentary canal. The study confirmed that enlargement of the carotid bodies is common in cases of pulmonary emphysema or sustained alveolar hypoxia with right ventricular hypertrophy. It is also common in cases of systemic hypertension with left ventricular hypertrophy. It was also revealed that enlargement of the carotid bodies may occur in cirrhosis of the liver. We believe this to be the first report of that association.
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PMID:The carotid bodies enlarge in some cases of cirrhosis of the liver. 820 96


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