Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Feb 15, 2016; 7(1): 48-58
Published online Feb 15, 2016. doi: 10.4291/wjgp.v7.i1.48
Alcoholic pancreatitis: New insights into the pathogenesis and treatment
Dahn L Clemens, Katrina J Schneider, Christopher K Arkfeld, Jaclyn R Grode, Mark A Wells, Shailender Singh
Dahn L Clemens, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-8098, United States
Dahn L Clemens, Nebraska-Western Iowa VA Heath Care System, University of Nebraska Medical Center, Omaha, NE 68198-8098, United States
Dahn L Clemens, Katrina J Schneider, Christopher K Arkfeld, Jaclyn R Grode, Mark A Wells, Shailender Singh, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-8098, United States
Author contributions: Clemens DL wrote the manuscript; all other authors contributed to the conceptual design of the manuscript, as well as the editing and final preparation.
Supported by Funds from the University of Nebraska Department of Internal Medicine, the Fred and Pamela Buffett Cancer Center, and the Nebraska Research Initiative (to Clemens DL); and by NIH, NIAAA grant AA020818 (to Arkfeld CK).
Conflict-of-interest statement: The authors declare no conflict of interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dahn L Clemens, PhD, Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198-8098, United States. dclemens@unmc.edu
Telephone: +1-402-9953738 Fax: +1-402-9950604
Received: June 29, 2015
Peer-review started: July 2, 2015
First decision: August 4, 2015
Revised: October 15, 2015
Accepted: November 10, 2015
Article in press: November 11, 2015
Published online: February 15, 2016
Abstract

Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis.

Keywords: Alcohol, Pancreatitis, Alcoholic pancreatitis, Ethanol metabolism, Acute pancreatitis, Fatty acid ethyl esters

Core tip: There is currently no specific pharmacotherapy for pancreatitis. Although ethanol abuse is commonly associated with both acute and chronic pancreatitis, ethanol does not itself cause pancreatitis. Instead it appears that ethanol and its metabolic by-products sensitize the pancreas to damage from other factors. Detailed understanding of the mechanisms by which ethanol sensitizes the pancreas to damage has identified a number of promising targets for therapy. It is hoped that further preclinical and clinical studies will lead to the development of successful treatment of both acute and chronic pancreatitis.