Individual susceptibility to alcoholic pancreatitis
Version of Record online: 12 MAR 2008
© 2007 The Authors
Journal of Gastroenterology and Hepatology
Special Issue: 2nd International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Kobe, Japan
Volume 23, Issue Supplement s1, pages S63–S68, March 2008
How to Cite
Apte, M. V., Pirola, R. C. and Wilson, J. S. (2008), Individual susceptibility to alcoholic pancreatitis. Journal of Gastroenterology and Hepatology, 23: S63–S68. doi: 10.1111/j.1440-1746.2007.05287.x
- Issue online: 12 MAR 2008
- Version of Record online: 12 MAR 2008
- Accepted for publication 17 November 2006.
- alcoholic pancreatitis;
- trigger factor
The observation that only a minority of heavy drinkers develop pancreatitis has prompted an intensive search for a trigger factor/cofactor/susceptibility factor that may precipitate a clinical attack. Putative susceptibility factors examined so far include diet, smoking, amount and type of alcohol consumed, the pattern of drinking and lipid intolerance. In addition, a range of inherited factors have been assessed including blood group antigens, human leukocyte antigen serotypes, alpha-1-antitrypsin phenotypes and several genotypes. The latter group comprises mutations/polymorphisms in genes related to alcohol-metabolizing enzymes, detoxifying enzymes, pancreatic digestive enzymes, pancreatic enzyme inhibitors, cystic fibrosis and cytokines. Disappointingly, despite this concerted research effort, no clear association has been established between the above factors and alcoholic pancreatitis. Experimentally, the secretagogue cholecystokinin (CCK) has been investigated as a candidate ‘trigger’ for alcoholic pancreatitis. However, the clinical relevance of CCK as a trigger factor has to be questioned, as it is difficult to envisage a situation in humans where abnormally high levels of CCK would be released into the circulation to trigger pancreatitis in alcoholics. In contrast, bacterial endotoxemia is a candidate cofactor that does have relevance to the clinical situation. Plasma lipopolysaccharide (LPS, an endotoxin) levels are significantly higher in drinkers (either after chronic alcohol intake or a single binge) compared to non-drinkers. We have recently shown that alcohol-fed animals challenged with otherwise innocuous doses of LPS exhibit significant pancreatic injury. Moreover, repeated LPS exposure in alcohol-fed rats leads to progressive injury to the gland characterized by significant pancreatic fibrosis. These studies support the concept that endotoxin may be an important factor in the initiation and progression of alcoholic pancreatitis. Scope remains for further studies examining proteins related to cellular anti-oxidant defenses, minor cystic fibrosis (CF) mutations and trans-heterozygosity involving a combination of mutations of different genes (such as CFTR alterations combined with SPINK1 or PRSS1 variants), as potential triggers of alcoholic pancreatitis.