Hepatology : official journal of the American Association for the Study of Liver Diseases
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Enhancing the portal venous blood flow (PVBF) has been shown to reduce portal pressure and intrahepatic vascular resistance and to improve liver function in isolated cirrhotic rodent livers in vitro. The aim of this study was to assess the short-term effect of mechanically pumping the portal inflow on hepatic microcirculation (HM), oxygenation, and function in an animal model of extensive hepatic fibrosis. New Zealand white rabbits underwent laparotomy and exposure of the liver: group 1 (n = 7) were normal controls; group 2 (n = 7) had hepatic fibrosis. ⋯ Flow in the HM improved (143 +/- 16 to 173 +/- 14 flux units, P =.006) and was associated with improved hepatic tissue oxygenation, tissue oxy-hemoglobin (HbO2) and cytochrome oxidase being increased by 24.4 +/- 7.5 and 5.65 +/- 2.30 micromol/L above the baseline value (P <.001), respectively. A 3-hour period of mechanical portal pumping produced a dramatic improvement in liver function, bilirubin (41.1 +/- 25.9 to 10.0 +/- 5.9 micromol/L, P =. 040), aspartate transaminase (AST) (135.5 +/- 52.3 to 56.3 +/- 19.8 U/L, P =.006) and lactate dehydrogenase (LDH) (2,030.1 +/- 796.3 to 1,309.8 +/- 431.6 IU/L, P =.006; prepumping vs. postpumping, all P <. 050). In conclusion, portal pumping in this rabbit model with extensive hepatic fibrosis improved liver parenchymal perfusion, oxygenation, and function.
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Cystic fibrosis transmembrane conductance regulator (CFTR), the cystic fibrosis (CF) gene product, functions as an adenosine 3', 5'-cyclic monophosphate (cAMP)-regulated chloride channel in the apical membrane of biliary epithelial cells, including gallbladder epithelial cells. It has been shown that triangle upF508, the most common CF mutation, impedes CFTR trafficking to the apical surface of epithelial cells. To elucidate the mechanisms of CF biliary disease, we examined structural features, CFTR expression, and chloride transport properties in gallbladder epithelial cells from nine triangle upF508 homozygous liver transplant recipients. ⋯ The CF cells exhibited a residual cAMP-dependent chloride secretion that was inversely correlated with ATP-induced chloride secretion, and almost completely blunted in the cells derived from microgallbladders. Our results suggest that epithelial structural alterations aggravate triangle upF508 CFTR mislocalization in the gallbladder epithelium. The associated decrease in residual cAMP-dependent chloride secretion may contribute to biliary damage despite the up-regulation of alternative chloride transport pathways.
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The health care system in the United States is at a turning point. We are experiencing a shift in focus from structure and process to outcomes, and from specific clinical outcomes to generic outcomes. ⋯ Rather, payers, employers, and patients themselves demand evidence that the health care system produces patients who feel better, can do more, and are confident about their health. These concepts, collectively referred to as Health-Related Quality of Life (HQL), are an important aspect of the natural history of liver diseases and an important means of assessing the results of therapeutic interventions.
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To better understand how gut-derived endotoxins influence alcohol-induced liver injury and the expression of inflammatory cytokines a new animal model was developed. After 2 weeks on a modified ethanol-containing liquid diet, some rats also were infused with endotoxin via osmotic minipumps for 4 additional weeks. Ethanol diet alone increased plasma endotoxin threefold to 9.3 pg/mL. ⋯ The mRNA expression of lipopolysaccharide binding protein (LBP) and CD14 endotoxin receptor was not significantly increased by chronic endotoxin treatment, contrasting with the marked elevation observed after acute endotoxin challenge. These results suggest that the tolerance observed despite sustained hepatic expression of proinflammatory cytokines is counteracted by the anti-inflammatory cytokines and by down-regulation of CD14 and LBP. Furthermore, a similar adaptation may occur in alcoholics with continuous endotoxemia.
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For reasons not yet determined, chronic liver disease (CLD) has been a leading cause of excess morbidity and mortality in central Harlem. We conducted a case series and case-control analysis of demographic, clinical, epidemiological, and alcohol-intake-related information from patients with CLD and age- and sex-matched hospitalized control patients. Patients' sera were tested for markers of viral hepatitis. ⋯ Alcohol and hepatitis viruses appear to be synergistically hepatotoxic; this synergy appears to explain both the high rate of CLD in central Harlem and the recent reductions in this rate. Persons at risk for chronic HBV and HCV infection should be counseled about their increased risk of CLD if they consume excessive alcohol. Morbidity and mortality from liver disease could be decreased further by a reduction in alcohol consumption among persons who have chronic HBV and HCV infection, avoidance of needle sharing, and hepatitis B vaccination.