Journal of clinical gastroenterology
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J. Clin. Gastroenterol. · Apr 2005
ReviewMild hypothermia for acute liver failure: a review of mechanisms of action.
Brain edema with intracranial hypertension is a major complication in patients with acute liver failure. Current therapies for this complication include a variety of pharmacologic and interventional measures, some of which are frequently associated with adverse effects or contraindications. Even though these measures usually allow the control of intracranial hypertension for a certain period of time, recurrence is common. ⋯ Several mechanisms by which mild hypothermia may prevent brain edema and intracranial hypertension in this condition have been disclosed and may include beneficial effects on ammonia metabolism, as well as on the disturbances of brain osmolarity, cerebrovascular hemodynamics, brain glucose metabolism, inflammation, and others. Improvement of systemic hemodynamics and amelioration of liver injury may be other benefits of the systemic induction of mild hypothermia, but the impact of potential adverse events, such as infection, should also be taken into account. At a time when mild hypothermia is increasingly used in several specialized centers, performance of a randomized controlled trial seems critical to confirm the benefits of mild hypothermia in acute liver failure and to provide adequate guidelines for its use.
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J. Clin. Gastroenterol. · Apr 2005
ReviewMolecular regulation of hepatobiliary transport systems: clinical implications for understanding and treating cholestasis.
Hepatobiliary transport systems are responsible for hepatic uptake and excretion of bile salts and other biliary constituents (eg, bilirubin) into bile. Hereditary transport defects can result in progressive familial and benign recurrent intrahepatic cholestasis. Exposure to acquired cholestatic injury (eg, drugs, hormones, proinflammatory cytokines, biliary obstruction or destruction) also results in altered expression and function of hepatic uptake and excretory systems, changes that may maintain and contribute to cholestasis and jaundice. ⋯ Alterations of hepatobiliary transporters and enzymes are not only relevant for a better understanding of the pathophysiology of cholestatic liver diseases, but may also represent important targets for pharmacotherapy. Drugs (eg, ursodeoxycholic acid, rifampicin) used to treat cholestatic liver diseases and pruritus may counteract cholestasis via stimulation of defective transporter expression and function. In addition, therapeutic strategies may be aimed at supporting and stimulating alternative detoxification pathways and elimination routes for bile salts in cholestasis.