Liver function tests can serve as the basis for accurate decision-making regarding the need for liver transplantation in the setting of acute failure or in patients with chronic liver disease. The liver metabolic breath test relies on measuring exhaled 13C tagged methacetin, which is metabolized only by the liver. Measuring this liver-specific substrate by means of molecular correlation spectroscopy is a rapid, non-invasive method
for assessing liver function at the point-of-care. The 13C methacetin breath test (MBT) is a powerful tool to aid clinical hepatologists in bedside decision-making. Our recent findings regarding the ability of point-of-care 13C MBT to assess the hepatic functional reserve in ABT-263 patients with acute and chronic liver disease are reviewed along with suggested treatment algorithms for common liver disorders. “
“Beta-catenin plays important roles in liver physiology and hepatocarcinogenesis. While studying the role of β-catenin in diet-induced steatohepatitis, we recently found that liver-specific β-catenin knockout (KO) mice exhibit intrahepatic cholestasis. This study was undertaken to further characterize the role of β-catenin in biliary physiology. KO mice and wild-type (WT) littermates were fed standard chow or a diet supplemented with 0.5% cholic acid for 2 weeks. Chow-fed KO
mice had higher serum and hepatic total bile acid levels and lower bile flow rate than WT mice. Expression BAY 73-4506 ic50 levels of bile acid biosynthetic genes were lower and levels of major bile acid exporters were similar, which therefore could not explain the KO phenotype. Despite loss of the tight junction protein claudin-2, KO mice had preserved functional integrity of tight junctions. KO mice had bile canalicular morphologic abnormalities as evidenced by staining for F-actin and zona occludens 1. Electron microscopy revealed dilated and tortuous bile canaliculi in KO livers along with decreased canalicular and sinusoidal
microvilli. KO mice on a cholic acid diet had higher hepatic and serum bile acid levels, bile ductular reaction, increased Farnesyltransferase pericellular fibrosis, and dilated, misshapen bile canaliculi. Compensatory changes in expression levels of several bile acid transporters and regulatory genes were found in KO livers. Conclusion: Liver-specific loss of β-catenin leads to defective bile canalicular morphology, bile secretory defect, and intrahepatic cholestasis. Thus, our results establish a critical role for β-catenin in biliary physiology. (HEPATOLOGY 2010) Beta-catenin, the primary effector of the canonical Wnt signaling pathway, plays critical roles in hepatocarcinogenesis and liver development.1-6 However, its role in adult liver physiology is not well understood. Cytoplasmic levels and localization of β-catenin are tightly regulated (reviewed in MacDonald et al.7). In the absence of Wnt signaling, β-catenin is bound in the cytoplasm by a multiprotein complex.