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

A 44-year-old man was admitted with symptoms compatible with Addison crisis. Abdominal computer tomography revealed extensive bilateral adrenal abscesses. Histoplasma capsulatum was cultured from a needle aspirate. The patient was HIV-seronegative and had no underlying malignancy. He may have acquired the infection during several stays in endemic areas in the United States, South America and Asia. The case was also remarkable for moderate brain atrophy, thrombosis of the portal and splenic veins and liver cirrhosis caused by alpha-1-antitrypsin deficiency (phenotype MZ). The patient recovered fully under substitution of adrenal hormones and antifungal treatment. He received intravenous amphotericin B (75 mg q24h) for 10 days, followed subsequently by oral treatment with itraconazole (400 mg q24h) over several months. Radiologic follow-up 9 and 18 months later showed a pronounced decrease of the inflammatory adrenal lesions.
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PMID:[Addison crisis due to bilateral adrenal gland histoplasmosis]. 799 62

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

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

Large cell liver cell dysplasia (LCD), a suggested preneoplastic change progressing to hepatocellular carcinoma, has been reported associated with alpha-1-antitrypsin deficiency which in some countries has an increased frequency of hepatocellular carcinoma. We examined the nonneoplastic liver from 13 alpha-1-antitrypsin deficiency patients for LCD and, using a labeled streptavidin-biotin technique, for immunohistochemical markers: AAT (1/200), hepatitis B surface (HBsAg, prediluted) and core (HBcAg, 1/400) antigens, and monoclonal (1/20) and polyclonal (1/40) mutant p53, a tumor suppressor gene. There were eight males and five females ranging from 2 mo to 76 yr (mean 40 yr). Nine livers showed cirrhosis, one chronic persistent hepatitis, one portal fibrosis, and two cholestatic hepatitis (in the two infants). The nine cases with LCD included five males and four females of mean age 46 yr (range, 17-71), eight with cirrhosis and one with portal fibrosis. Only one liver with LCD and cirrhosis had HBcAg in cirrhotic and dysplastic cells. No patient had developed hepatocellular carcinoma. All 13 livers were immunonegative for HBsAg and mutant p53, and immunopositive for AAT present in normal, cirrhotic, and dysplastic liver cells. Thus, LCD was identified in 82% of adult alpha-1-antitrypsin deficiency livers (69% including infantile patients), 89% with cirrhosis, and none with malignancy. HB expression was rarely present; serology for HB and/or hepatitis C was positive in 46% adults. Immunoreactive AAT was present in dysplastic cells. p53 gene mutations do not appear to have a role in the pathogenesis of LCD in alpha-1-antitrypsin deficiency.
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PMID:Liver cell dysplasia in alpha-1-antitrypsin deficiency. 815 50

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

Analysis of 5180 liver transplant cases from 37 liver transplant centers in the United States (1982-1991) shows an overall one-year survival rate of 79.4 +/- 0.6% and a five-year survival rate of 69.2 +/- 0.9%. There was marked improvement in the one-year survival rate after liver transplantation from 36.0 +/- 9.6% in 1982 to 85.0 +/- 1.8% in 1991. One-year survival rates after liver transplantation for postnecrotic cirrhosis, primary biliary cirrhosis, alcoholic cirrhosis, primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, and Wilson's disease ranged from 78.4 +/- 1.0% to 84.2 +/- 1.5% and five-year survival rates from 68.6 +/- 3.8% to 79.2 +/- 5.3%. Survival rates after liver transplantation for hemochromatosis were poor--a one-year survival rate of 53.8 +/- 6.8% and a five year survival rate of 43.1 +/- 11%. One- and five-year survival rates for the 0-13 years age group were 74.6 +/- 2.8% and 66.7 +/- 3.4%; for the 14-37 years age group, 83.3 +/- 1.2% and 73.8 +/- 1.8%; for the 38-54 years age group, 79.6 +/- 0.8% and 69.7 +/- 1.3%; for the 55-63 years age group, 76.0 +/- 1.4% and 63.0 +/- 3.1%; and for the 64-77 years age group, 76.5 +/- 3.0% and 65.4 +/- 4.6%.
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PMID:An analysis of liver transplant experience from 37 transplant centers as reported to Medicare. 821 49

Alpha-1-antitrypsin is a glycoprotein which inactivates proteolytic enzymes, especially neutrophil elastase. Infants deficient in this enzyme commonly develop neonatal hepatitis. In adults, the deficiency typically results in emphysema. Only rarely will an adult manifest liver disease. We present a case of adult liver cirrhosis due to Alpha-1-antitrypsin deficiency in a 63-year-old man. Manifestations of alpha-1-antitrypsin deficiency and liver disease are discussed.
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PMID:Alpha-1-antitrypsin deficiency: rare cause of adult cirrhosis--a case report. 842 51

Proliferation of preexisting bile ducts, ductular metaplasia of hepatocytes and proliferation and differentiation of liver stem cells are discussed in the pathogenesis of neoductular structures in the liver. Under the condition of experimental bile duct obstruction and in extrahepatic bile duct stenosis neoductular structures are first the result of proliferation and sprouting of preexisting ducts and cholangioles. Especially in later stages of cholestasis but also in other chronic progredient liver diseases such as chronic alcoholic liver disease and chronic active hepatitis periportal hepatocytes may show a phenotypic shift towards ductular epithelia. In postnatal liver diseases hepatocytes first express keratin 7 and later keratin 19 during ductular transdifferentiation. This is in contrast to embryonal cholangiogenesis. In alpha-1-antitrypsin-deficiency, hemochromatosis, Wilson's disease, and chronic active hepatitis B cellular deposites typically located in hepatocytes such as alpha-1-AT, siderin, copper, HBs-Ag, and HBc-Ag can also be found in neoductular cells close to hepatocytes. These deposites seem to be retained during the ductular transdifferentiation of hepatocytes. Expression of bile duct-type integrin subtypes and TGF beta 1 in neoductular cells are involved in the changing parenchymal/mesenchymal interplay during neoductogenesis, resulting in periductular basal membrane and periductular fibrosis. In FNH the ductular transdifferentiation of hepatocytes is integrated in the histogenesis of micronodules and portal tract equivalents of these tumor-like lesions. Ductular structures in hepatoblastomas and especially in combined hepatocellular and cholangiocarcinomas (CHCC) may reflect the common embryologic derivation of hepatocytes and biliary epithelia. Non-neoplastic liver tissue in resection specimens of our CHCC showed a lower rate of cirrhosis, and a significantly higher Ki 67-LI of neoductular cells compared to liver tissue in resection specimens of HCC and liver metastases. 3 of 10 CHCC had developed in alpha-1-AT-deficiency, in which this protease-inhibitor was predominantly retained in periportal hepatocytes. These findings in non-neoplastic tumor-bearing liver tissue suggest that CHCC include a special histogenic type of primary liver carcinoma which in analogy to some experimental liver tumors might develop from periportal parenchymal cells.
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PMID:[Hepatic neoductules]. 860 Jun 93

Irreversible liver cirrhosis was induced in rats by supplementing their diet with 0.02% azathioprine and intubating them twice a week with carbon tetrachloride in corn oil. Over period of 3 mo, intoxicated rats showed an atypical acute-phase reaction (APR). The relative concentrations of haptoglobin, beta-lipoprotein, alpha-1-antitrypsin, an unknown peak "X, " and transferrin increased exponentially following a mild initial drop, while albumin, C3c + C3, alpha-1-acid glycoprotein, alpha-1-lipoprotein, and macroglobulin declined continually during the experiment. The accumulated peritoneal fluid was found to contain a similar spectrum of APR proteins. On the other hand, histological examination revealed gradual liver damage manifested as a gradual increase in the areas of collagen separating liver cells, and at the end of the experiment, severe liver damage was evident with isolated hepatocytes in a matrix of collagen. The available data point to the disparity that exists between the physical status of hepatocytes and their biochemical function, which suggests that the remaining metabolically fatigued hepatocytes of the cirrhotic liver continue to biosynthesize and release elevated concentrations of some secretable APR proteins and less of others. Changes in the spectrum of APR plasma components during the progression of inflammatory or physical lesion remain a valid biochemical measure of the pathological function of the acutely intoxicated liver. Partial hepatectomy (PH) of cirrhotic liver displayed a mute APR and no regenerative activity of the remnant hepatic tissue, most likely due to the substantial depletion of hepatic DNA and possible chemical damage to DNA of the remaining viable hepatocytes. A possible cause for the depressed APR to the surgical insult of PH is that the initial azathioprine-CCl4 intoxication had maximally affected APR gene expression and a second injury would then elicit minimal further changes in mRNA levels. Thus, in a compounded pathological condition, the initial inflammatory stimulus on various pre-rRNAs, rRNAs, and mRNAs is rate-limiting to the hepatic biosynthesis and secretion of APR proteins and may not respond linearly, if at all, to a second stimulus.
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PMID:Acute-phase response in rat to carbon tetrachloride-azathioprine induced cirrhosis and partial hepatectomy of cirrhotic liver. 861 26


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