DD duration has not changed over the last 60 years in Italy, but the number of IBD patients with a longer DD significantly decreased. Older age at diagnosis and a complicated disease at CD diagnosis are risk factors for longer DD.

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We studied the effects of alkaline phosphatase (AP) on the secretory processes of the rat intrahepatic biliary epithelium as well as the role of the intrahepatic biliary epithelium in the uptake and biliary secretion of exogenous AP. The effects of acute and chronic administration of AP on bile secretory parameters were investigated in vivo in normal and bile duct ligated (BDL) rats and in vitro in isolated rat bile duct units (IBDU). In vivo, acute AP administration decreased bile flow and biliary bicarbonate excretion and abolished secretin choleresis in BDL rats but not in normal rats. On the contrary, the AP inhibitor, levamisole, increased in BDL rat bile flow and biliary bicarbonate excretion. The intrahepatic biliary epithelium plays a key role in determining the final composition of bile reaching the duodenum through the secretion and/or reabsorption of bile constituents. 1,2 Bicarbonate secretion in bile, a major function of the biliary epithelium, is driven by the apically located Cl Ϫ /HCO 3 Ϫ exchanger, which is functionally coupled with the cystic fibrosis transmembrane regulator (CFTR). 1-5 Secretin induces ductal choleresis by activating, via the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway, the CFTR and subsequently stimulating the Cl Ϫ /HCO 3 Ϫ exchanger. [3][4][5] We have recently shown that protein kinase A (PKA) is essential in the mechanism of secretin choleresis by showing that Rp-cAMPs, a specific PKA inhibitor, blocks both secretin-induced bicarbonate-rich choleresis and stimulation of the Cl Ϫ /HCO 3 Ϫ exchanger. 5 Once secretin is removed, the run-down of secretory stimulus is driven by the protein phosphatases 1 and/or 2A, because their inhibitor, okadaic acid, induces persistence of secretion even after removal of the hormone. 5 These experiments indicate that the process of secretin choleresis is modulated by a balance between the activities of kinases and phosphatases, with the object of this balance being the reversible phosphorylation of CFTR. In other cell types expressing CFTR, the basal activity of protein phosphatases is important in maintaining CFTR in the quiescent status. 6-8 Indeed, when protein phosphatases are pharmacologically blocked, CFTR undergoes activation with opening of Cl Ϫ conductance. 6 The secretory processes of the intrahepatic biliary epithelium are also regulated by adenosine triphosphate (ATP), which modulates the activities of CFTR and other Cl Ϫ channels. 9,10 Alkaline phosphatase (AP) is a nonspecific protein phosphatase whose function is scarcely known. AP is markedly expressed in the apical pole of hepatocytes and cholangiocytes and is secreted in bile in large amounts. 11-14 Hepatic AP displays the function of ATPase, 11 and a role in endotoxin detoxification has recently been shown. 15 Although AP could theoretically influence the secretory processes of the biliary epithelium by acting as ATPase or by nonspecific protein phosphatase, the role of this enzyme in the regulation of processes underlying bile formation has not yet b...

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The cohort we examined is small, but fistulectomy combined with repeated perifistular injections of infliximab appears to be safe and may help in fistula healing. However, in most patients, permanent closure of all fistulas is not achieved.