This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Alcohol-induced pancreatitis is a chronic and disabling condition characterized by recurrent flares of acute pancreatitis. The pathophysiologic mechanism(s) underlying these recurrent flares are not fully known. In preliminary studies, 55% of subjects with alcohol-induced pancreatitis admitted with a flare of abdominal pain were found to have biliary microlithiasis. Biliary microlithiasis is known to be highly prevalent in those with idiopathic recurrent pancreatitis (1;2). Dissolution of biliary microlithiasis reduces the frequency of acute attacks of pancreatitis in this population. Based on these, the following novel hypothesis is proposed:Biliary microlithiasis is present in a subset of subjects with alcohol-induced pancreatitis and contributes to recurrent flares of acute pancreatitis in such patients. Therefore, its dissolution with urso-deoxycholic acid (UDCA) will reduce the frequency of acute flares of pancreatitis in this population.There are two main objectives of this R21 proposal which are the first steps to testing this hypothesis. These are:1. TO DEFINE THE PREVALENCE AND TYPES OF BILIARY MICROLITHIASIS IN SUBJECTS WITH ALCOHOL-INDUCED PANCREATITISSpecific Aim 1: To define the point prevalence of various types of biliary microlithiasis in subjects with alcohol-induced pancreatitis.2. TO PROVIDE 'PROOF OF CONCEPT' THAT UDCA CAN CLEAR THE BILE OF MICRO-LITHIASIS IN SUBJECTS WITH ALCOHOL-INDUCED PANCREATITIS AND IDENTIFY THE FACTORS ASSOCIATED WITH SUCCESSFUL CLEARANCE OF MICROLITHIASISSpecific Aim 2: To perform a PHASE II PILOT study of UDCA (10 mg/kg/day) to define its biologic effectiveness for clearance of biliary microlithiasis in subjects with alcohol-induced pancreatitis and biliary microlithiasis.
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