Hepatology : official journal of the American Association for the Study of Liver Diseases
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Randomized Controlled Trial
Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid.
Intrahepatic cholestasis of pregnancy (ICP) is characterized by troublesome maternal pruritus, elevated serum bile acids (> or =10 micromol/L) and increased fetal risk. Recently we determined a cutoff level of serum bile acids, > or =40 micromol/L, to be associated with impaired fetal outcome. We have now studied the effects of ursodeoxycholic acid (UDCA) and dexamethasone on pruritus, biochemical markers of cholestasis, and fetal complication rates in a double-blind, placebo-controlled trial. ⋯ In a subgroup analysis of ICP women with serum bile acids > or =40 micromol/L at inclusion (n = 34), UDCA had significant effects on pruritus (-75%), bile acids (-79%), ALT (-80%), and bilirubin (-50%) as well, but not on fetal complication rates. Dexamethasone yielded no alleviation of pruritus or reduction of ALT and was less effective than UDCA at reducing bile acids and bilirubin. In conclusion, 3 weeks of UDCA treatment improved some biochemical markers of ICP irrespective of disease severity, whereas significant relief from pruritus and marked reduction of serum bile acids were only found in patients with severe ICP.
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Randomized Controlled Trial Comparative Study Clinical Trial
A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis.
The administration of albumin improves circulatory function, prevents hepatorenal syndrome, and reduces hospital mortality in patients with cirrhosis and spontaneous bacterial peritonitis. This randomized unblinded pilot study compared the effect of albumin (10 patients) and the synthetic plasma expander hydroxyethyl starch 200/0.5 (10 patients) on the systemic hemodynamics of patients with spontaneous bacterial peritonitis. Baseline measurements were performed within 12 hours after diagnosis of infection. ⋯ These data suggest an effect of albumin on endothelial function. In conclusion, albumin but not hydroxyethyl starch improves systemic hemodynamics in patients with spontaneous bacterial peritonitis. This effect is due not only to volume expansion but also to an action on the peripheral arterial circulation.
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Induction of hepatic phase I/II detoxification enzymes and alternative excretory pumps may limit hepatocellular accumulation of toxic biliary compounds in cholestasis. Because the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate involved enzymes and transporters, we aimed to induce adaptive alternative pathways with different CAR and PXR agonists in vivo. Mice were treated with the CAR agonists phenobarbital and 1,4-bis-[2-(3,5-dichlorpyridyloxy)]benzene, as well as the PXR agonists atorvastatin and pregnenolone-16alpha-carbonitrile. ⋯ These changes were accompanied by reduced serum levels of bilirubin and bile acids in healthy and CBDL mice and by increased levels of polyhydroxylated bile acids in serum and urine of cholestatic mice. Atorvastatin significantly increased Oatp2, Mdr2, and Asbt, while other transporters and enzymes were moderately affected. In conclusion, administration of specific CAR or PXR ligands results in coordinated stimulation of major hepatic bile acid/bilirubin metabolizing and detoxifying enzymes and hepatic key alternative efflux systems, effects that are predicted to counteract cholestasis.
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Patients with obstructive sleep apnea (OSA) are at risk for the development of fatty liver as a result of being overweight. Several data suggest that OSA per se could be a risk factor of liver injury; ischemic hepatitis during OSA has been reported, and OSA is an independent risk factor for insulin resistance. Therefore, we investigated liver damage and potential mechanisms in 163 consecutive nondrinking patients with nocturnal polysomnographic recording for clinical suspicion of OSA. ⋯ In conclusion, severe OSA is a risk factor for elevated liver enzymes and steatohepatitis independent of body weight. Promotion of insulin resistance is probably involved. Further studies are needed to determine whether hypoxia contributes directly to liver injury.
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Few data exist concerning survival after the diagnosis of hepatopulmonary syndrome (HPS). Although orthotopic liver transplantation (OLT) frequently results in complete resolution of HPS, the relationship between transplantation and survival has not been described. The study rationale was to describe long-term survival in patients with HPS. ⋯ Baseline PaO(2)