Bile as a key aetiological factor of acute but not chronic pancreatitis: a possible theory revealed

It has been known for more than a century that bile acids and gallstones may represent an aetiological factor in acute pancreatitis (AP). Importantly, while bile is responsible for around 40% of AP, its aetiological role in the chronic form of the disease (CP) is close to zero. Only 4% of patients suffering from CP have gallstones, and it is still not clear whether this is only an association or whether bile or gallstones play any pathophysiological role in the development of the chronic inflammation. In this issue of The Journal of Physiology, Ferdek et al. have offered the first explanation for this phenomenon at the cellular level (Ferdek et al. 2016). They have shown for the first time that bile acids elicit dramatic necrosis in pancreatic stellate cells (PSCs) but not in pancreatic acinar cells (PACs). In the presence of calcium, sodium cholate induces 73% necrosis in PSCs but only around 10% in PACs, suggesting that the PSC, the key player in the extracellular matrix in the pancreas, is the cell type most endangered by bile (Ferdek et al. 2016). Since the effects of bile acids on pancreatic ductal cells (PDCs) have also been characterized, the chronological events in how bile acids affect the exocrine pancreas and induce acute but not chronic pancreatitis can be followed (Fig. 1).