The pathogenesis of pancreatic
fibrosis, a characteristic feature of alcohol-induced
chronic pancreatitis, has received increasing attention over the past few years, largely due to the identification and characterization of stellate cells in the pancreas. These cells are morphologically similar to hepatic stellate cells, the principal effector cells in
liver fibrosis. The role of pancreatic stellate cells (PSCs) in alcoholic pancreatic
fibrosis has been studied using 2 approaches: (i) in vivo studies using pancreatic tissue from patients with alcohol-induced
chronic pancreatitis and from animal models of experimental
pancreatitis and (ii) in vitro studies using cultured PSCs. These studies indicate that PSCs are activated early in the course of pancreatic injury and are the predominant source of
collagen in the fibrotic pancreas. Several factors that may be responsible for mediating PSC activation during chronic alcohol exposure have also been identified. From the findings to date, it may be speculated that the pathogenesis of alcoholic pancreatic
fibrosis may involve 2 pathways: (i) a necroinflammatory pathway involving
cytokine release and PSC activation and (ii) a nonnecroinflammatory pathway involving direct activation of PSCs by
ethanol via its metabolism to
acetaldehyde and the generation of
oxidant stress.