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)

Cirrhosis is characterized by fibrogenesis, hepatocyte necrosis and the formation of regenerative nodules. Modulation of the epidermal growth factor receptor is an early event during regeneration. We have recently demonstrated alterations in the epidermal growth factor receptor during the development of biliary cirrhosis. The aim of the present study was to compare epidermal growth factor receptor distribution, expression and binding in biliary cirrhosis to that occurring in micronodular cirrhosis induced by phenobarbital/CCl4 exposition. Biliary cirrhosis and micronodular cirrhosis had similar functional impairment as assessed by the aminopyrine breath test. Epidermal growth factor receptor binding capacity was reduced in both models (control vs micronodular cirrhosis vs biliary cirrhosis: (mean +/- 1 SD) 60 +/- 22 vs 16 +/- 12 vs 27 +/- 9 fmol/mg protein, p < 0.05), while the binding constant was increased in biliary cirrhosis only. The receptor mass in plasma membrane, determined by Western blotting, was not changed. Distribution of epidermal growth factor receptor was assessed immunohistochemically on tissue sections. In both models, cytoplasmic staining was decreased and basolateral plasma membrane labeling was maintained. Nuclear localization was found in biliary cirrhosis only. In conclusion, in both models, cirrhosis induces an alteration in the binding properties, but not in the number of epidermal growth factor receptors in the plasma membrane. The loss of cytoplasmic epidermal growth factor receptor could reflect alterations in expression and/or in intracellular trafficking. This is supported by the reduced mRNA steady state levels for epidermal growth factor receptor which were found in both models, presumably representing down-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effect of micronodular and biliary cirrhosis on epidermal growth factor receptor expression in the rat. 769 65

The growth in liver transplantations recorded by the Pitt-UNOS Liver Transplant Registry since October 1987 continues as does the net growth of new centers. Characteristics of pediatric recipients in 1994 were compared to those of previous years and no significant differences were found for gender, race or age. The majority of pediatric recipients in 1994 awaited transplantation at home. The most common indication for liver transplantation in children was bilary atresia, though the proportion of recipients with this primary liver disease decreased significantly. Significant increases were noted in the proportions of pediatric recipients with autoimmune disease (though this remains a relatively uncommon indication) and fulminant liver failure. There was a significant decrease in the proportion of children who received ABO-incompatible livers. Many of the characteristics examined for adult recipients changed over time. The proportion of male recipients continued to increase. The mean age of adult recipients continued to increase, likely contributing to the increased prevalence of positive CMV-serology. The proportion of adult recipients awaiting transplantation outside the hospital increased over time. The increase in the proportion of multiorgan transplantations was in large part due to the increased reporting of bone marrow/liver transplants in 1994. Hepatitis non-A, non-B, or C and alcoholic liver disease were the most common reasons for LTX. The proportions of recipients with hepatitis B, fulminant liver failure and malignancies, indications with the poorest survival, all declined significantly. The cumulative probability of surviving (without retransplantation) for 7 years after initial transplantation was 0.70 (0.57) for pediatric recipients. Despite changes in recipient characteristics, the one-year survival for pediatric recipients did not change significantly over time. Significant differences in survival, unadjusted for other factors, were found by age (the youngest recipients had the worst survival), location awaiting transplantation (greater medical intervention just prior to transplantation led to poorer survival), multiorgan transplantation, primary liver disease (survival was worst for recipients transplanted due to malignancies, and best for patients with metabolic diseases), and donor/recipient ABO matching (survival was best for recipients of livers from donors with the same blood type). These results are similar to those previously reported for 4- and 5-year survivals. The cumulative probability of adults surviving (without retransplantation) for 7 years following LTX was 0.59 (0.52). Significant differences in survival, unadjusted for other factors, were found for year of transplantation (recipients in 1994 had better one-year survival than those transplanted in previous years), sex (males had worse survival than females), race (Blacks and Asians had the poorest survivals), age (recipients 50 years of age and older had the poorest survival), location awaiting transplantation (greater medical intervention just prior to transplantation led to poorer survival), multiorgan transplantation (recipients of organs in addition to the liver had worse patient survival than recipients of liver only), and primary liver disease (the best survival was for cirrhosis due to cryptogenic or cholestatic cirrhosis, the poorest survival was for malignancies and hepatitis B). Similar results were also reported previously for 4- and 5-year survivals.
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PMID:An update on liver transplantation in the United States: recipient characteristics and outcome. 879 52

Five weeks after common bile duct ligation (CBL), Wistar rats had histologically verified liver cirrhosis with sodium retention but without ascites. Plasma concentrations of vasopressin and aldosterone were normal. Glomerular filtration rate was unchanged, although renal plasma flow was increased. A test dose of furosemide (7.5 mg/kg body wt iv) produced significantly greater diuretic (+59%) and natriuretic (+66%) responses in Wistar CBL rats than in sham-operated controls. Stereological examination of kidneys demonstrated a 47% increase in the volume of the inner stripe of the outer medulla, with a 55% increase in the volume of thick ascending limb of Henle's loop (TALH) epithelium in cirrhotic Wistar rats relative to controls. CBL produced a similar degree of liver cirrhosis in vasopressin-deficient Brattleboro rats. However, both functional and structural renal changes observed in cirrhotic Wistar rats were absent in vasopressin-deficient cirrhotic Brattleboro rats. These results suggest a permissive action of vasopressin for the adaptive changes in TALH in rats with experimental liver cirrhosis. Our results are consistent with the hypothesis that increased sodium chloride reabsorption in the TALH may contribute to the early sodium retention that precedes ascites formation in rats with secondary biliary liver cirrhosis.
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PMID:Functional and structural changes in the thick ascending limb of Henle's loop in rats with liver cirrhosis. 927 40

Four Puerto Rican sisters had recurrent prolonged cholestasis of pregnancy without preexisting or intercurrent hepatic disorders. Available information was reviewed on the course, mechanism, and sequelae of prolonged recurrent cholestasis after 14 pregnancies in the 4 sisters. Etiologic, clinical, laboratory, radiological, and morphological studies of the liver and biliary tract were assessed. Each sister had contraceptive pill-induced pruritus. Prolonged recurrent cholestasis in the eldest sister was followed by cirrhosis and death. The second and third sisters had biopsy evidence of portal triaditis and fibrosis after five and three pregnancies, respectively. Intrahepatic cholestatic cirrhosis was present after three pregnancies in the youngest sister, necessitating an orthotopic liver transplantation; a posttransplantation pregnancy was also associated with prolonged cholestasis. Recurrent prolonged intrahepatic cholestasis of pregnancy was followed by periportal fibrosis or cirrhosis in 4 sisters. This finding suggests that patients with prolonged cholestasis after pregnancy should be followed up for evidence of ongoing liver disease, should be counseled on the potential of recurrence and disease progression in future pregnancies, and should alert family members at risk of possible occurrence of the syndrome.
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PMID:Recurrent familial prolonged intrahepatic cholestasis of pregnancy associated with chronic liver disease. 961 63

Biliary cirrhosis in the rat triggers intrapulmonary vasodilatation and gas exchange abnormalities that characterize the hepatopulmonary syndrome. This vasodilatation correlates with increased levels of pulmonary microcirculatory endothelial nitric oxide synthase (eNOS) and hepatic and plasma endothelin-1 (ET-1). Prehepatic portal hypertension induced by portal vein ligation (PVL) does not cause similar changes, suggesting that ET-1 in cirrhosis may modulate pulmonary eNOS and vascular tone. We assessed whether ET-1 altered eNOS expression and nitric oxide production in bovine pulmonary artery endothelial cells (BPAECs) and if a 2-wk low-level intravenous ET-1 infusion in PVL animals modulated pulmonary eNOS levels, microcirculatory tone, and gas exchange. ET-1 caused a 2.5-fold increase in eNOS protein in BPAECs, inhibitable with an endothelin B receptor antagonist, and an increase in eNOS mRNA and nitrite production. ET-1 infusion in PVL animals caused increased pulmonary eNOS levels, intrapulmonary vasodilatation, and gas exchange abnormalities without increasing pulmonary arterial pressure. ET-1 produced during hepatic injury may contribute to the hepatopulmonary syndrome by modulating eNOS and inducing pulmonary microcicrulatory vasodilatation.
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PMID:Endothelin-1 stimulation of endothelial nitric oxide synthase in the pathogenesis of hepatopulmonary syndrome. 1056 99

Liver transplantation (LT) for malignant tumors should be accepted if, with adequate case selection, long-term results are similar to those in patients transplanted for benign diseases. The aim of the present study was to reexamine selection criteria for LT in malignant diseases with particular emphasis on hepatocellular carcinoma (HCC) in cirrhosis. One hundred-three of 369 patients transplanted in our unit had HCC in cirrhosis (28%), 15 of which were incidental tumors, and 234 patients underwent LT for non-cholestatic cirrhosis. Pretransplant arterial chemoembolization(TACE) was performed in 36 cases (41%) of known HCC. Only early,well-delimited tumors in advanced cirrhosis with no extrahepatic disease were accepted for LT. Hepatocellular carcinoma characteristics included mean tumor size (3.1 cm), multiple (59%), bilobular involvement (31%), and vascular invasion (9.2%). Postoperative mortality was 4%. Median follow-up was 67.5 months. Tumor recurrence rate was 14.5%, 33% (5/15) in incidental tumors and 11.4% (10/88) in known HCC and by tumor stage (pTNM): 7.7% (1/13) in stage I, 16.7%(5/30) in stage II, 15% (3/20) in stage III, and 17% (6/35) in stage IV. Mean time for recurrence was 20.6 months. Tumoral vascular invasion, tumor differentiation, and satellite tumors were significant factors for tumor recurrence in univariate analysis, whereas tumor vascular invasion was the only significant factor for tumor recurrence in multivariate analysis. Actuarial survival rates at 1, 3, and 5 years were 81%, 66%, 58%, respectively, in patients with HCC and were similar to those of cirrhotic patients 76%, 67%, 63%, respectively. In conclusion, patients with early HCC in cirrhosis are good candidates for LT; results are similar when compared with those of cirrhotic patients without tumor. Liver transplantation for other malignancies is admitted only in fibrolamellar hepatoma, hepatoblastoma, epithelioid hemangioendothelioma without extrahepatic disease, and in metastases from carcinoid tumors.
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PMID:Liver transplantation for malignant diseases: selection and pattern of recurrence. 1186 57

Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, catalyzing the oxidative cleavage of heme molecules to biliverdin, carbon monoxide, and iron. The present study was designed to investigate the role of HO-1 in the pathogenesis of renal dysfunction during cirrhosis. Biliary cirrhosis was induced in rats by common bile duct ligation (CBDL). Animals were studied 2 and 5 wk after surgery. In kidney from CBDL rats, HO-1 protein expression increased slightly at 2 wk but was abolished at 5 wk. In addition, we confirmed histologically that HO-1 expression was suppressed in renal tubules and interlobular arterioles in 5-wk-old CBDL rats. Conversely, HO-1 expression in liver was strongly increased. Consistent with the development of cirrhosis and renal dysfunction mean arterial pressure (MAP), glomerular filtration rate (GFR), and renal blood flow (RBF) were decreased in CBDL rats compared with sham-operated controls. In sham rats, treatment with the selective HO inhibitor zinc protoporphyrin markedly decreased GFR and RBF to values similar to those measured in CBDL rats without decreasing MAP. In conclusion, decreased renal HO-1 expression contributes to deteriorated renal function and hemodynamics during cirrhosis. This finding provides a novel mechanism for the pathophysiology of renal dysfunction during cirrhosis.
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PMID:Decreased renal heme oxygenase-1 expression contributes to decreased renal function during cirrhosis. 1237 89

This study aims at establishing the pattern of liver cirrhosis. Histology slides and duplicate copies of reports were retrieved and re-examined while fresh sections were processed from original paraffin blocks when necessary. Cirrhosis was the second commonest cause of chronic liver disease after hepatocellular carcinoma. The commonest morphological type was macronodular cirrhosis. Micronodular cirrhosis is not as common in black Africans as among the Caucasians. This is not unexpected since alcoholic liver disease that is of aetiopathogenetic importance is also not as common as what is often found in Causasians. Biliary cirrhosis was reported in an 8 months old girl consequent upon congenital absence of gallbladder and biliary tree. There was male preponderance in the occurrence of cirrhosis with a male, female ratio of 2.5:1. The incidence gradually increased from early adult life but was highest in the middle age especially between the age group of 51-60 years and subsequently dropped sharply. Adequate diagnostic facilities should be provided to determine the incidence of hepatotropic viruses and their contribution to the incidence of chronic liver diseases. Case-controlled studies should be carried out to determine the role of local cultural practices on hepatocellular injury and the development of chronic liver disease.
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PMID:Histopathological assessment of the pattern of liver cirrhosis in a tropical population. 1502 82

Biliary cirrhosis in the rat triggers intrapulmonary vasodilatation and gas-exchange abnormalities that characterize the hepatopulmonary syndrome. This vasodilatation correlates with increased levels of pulmonary microcirculatory endothelial NO synthase (eNOS) and hepatic and plasma endothelin-1 (ET-1). Importantly, during cirrhosis, the pulmonary vascular responses to acute hypoxia are blunted. The purpose of this work was to examine the pulmonary vascular responses and adaptations to the combination of liver cirrhosis and chronic hypoxia (CH). In addition to hemodynamic measurements, we investigated whether pulmonary expression changes of eNOS, ET-1 and its receptors (endothelin A and B), or heme oxygenase 1 in experimental cirrhosis affect the development of hypoxic pulmonary hypertension. We induced cirrhosis in male Sprague-Dawley rats using common bile duct ligation (CBDL) and exposed them to CH (inspired PO2 approximately 76 Torr) or maintained them in Denver (Den, inspired PO2 approximately 122 Torr) for 3 wk. Our data show 1) CBDL-CH rats had a persistent blunted hypoxic pulmonary vasoconstriction similar to CBDL-Den; 2) the development of hypoxic pulmonary hypertension was completely prevented in the CBDL-CH rats, as indicated by normal pulmonary arterial pressure and lack of right ventricular hypertrophy and pulmonary arteriole remodeling; and 3) selective increases in expression of ET-1, pulmonary endothelin B receptor, eNOS, and heme oxygenase 1 are potential mechanisms of protection against hypoxic pulmonary hypertension in the CBDL-CH rats. These data demonstrate that unique and undefined hepatic-pulmonary interactions occur during liver cirrhosis and chronic hypoxia. Understanding these interactions may provide important information for the prevention and treatment of pulmonary hypertension.
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PMID:Hypoxic pulmonary hypertension is prevented in rats with common bile duct ligation. 1551 65

The frequency and the outcome of patients with portal vein (PV) complications in the long-term course after pediatric living donor liver transplantation (LDLT) have rarely been reported. Between June 1990 and September 2003, 527 pediatric patients underwent primary LDLT with left lobe grafts, among which 479 patients with functioning grafts at 3 months after LDLT were included in this analysis. The ages ranged from 29 days to 17 years, 3 months (median: 1 year, 9 months) and body weight from 3.1 kg to 62.4 kg (median: 9.6 kg). Biliary cirrhosis was the most common cause for LDLT (81%). The PV was anastomosed with or without a vein graft. Thirty-nine patients (8%) showed a PV complication (stenosis: 16; obstruction: 17; thrombus: 2; twist: 3). Their ages ranged from 4 months to 17 years, 3 months (median: 1 year) and their body weight from 3.8 kg to 44.8 kg (median: 8.5 kg) at operation. PV complications were detected between 4 and 116 months (median: 14 months) after the transplant. Splenomegaly and decreased platelet counts were observed in more than 90% of the patients with a PV complication. In 27 patients (71%), interventional venoplasty was successful. Eleven patients had obstruction of the PV (2.3%) including three who showed cirrhosis; one with severe pulmonary hypertension; one death after retransplantation; and one alive after retransplantation. Moderate fibrosis was found in two patients at 3 and 2 years after the procedure, one of whom had the complication of a moderate intrapulmonary shunt. Early detection of PV stenosis with these two markers can lead to successful angioplasty and avoid graft loss.
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PMID:Portal vein complications in the long-term course after pediatric living donor liver transplantation. 1584 48


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