Antiproteases in the treatment of acute pancreatitis.

The pathogenesis of acute pancreatitis relates to the inappropriate activation of trypsinogen to trypsin and a lack of the prompt elimination of the active trypsin inside the pancreas. Therefore, trypsin is believed to be the key enzyme in the initiation and exacerbation of acute pancreatitis by activating pancreatic zymogens. The activation of digestive enzymes causes pancreatic injury and results in an inflammatory response. The acute inflammatory response in the pancreas induces the systemic production of cytokines causing substantial tissue damage, and may progress beyond the pancreas to a systemic inflammatory response syndrome (SIRS), multi-organ failure (MOF) or death [1]. In several studies, protease inhibitors have not been shown to be of significant value in the treatment of acute pancreatitis and are not available in the United States [2]. Several guidelines [3, 4, 5, 6, 7, 8, 9, 10, 11, 12] on the treatment of acute pancreatitis do not recommend them and the debate about the use of protease inhibitors is mentioned. On the other hand, several studies on prophylaxis with protease inhibitors for pancreatitis induced by endoscopic retrograde cholangiopancreatography (ERCP) have recently revealed their favorable effects in preventing serum pancreatic enzyme elevation, abdominal pain or the onset of pancreatitis [13, 14, 15, 16, 17, 18, 19, 20, 21]. Also, several meta-analyses have shown that gabexate mesilate significantly reduced the complications of acute pancreatitis, such as sepsis and bleeding [22, 23]. In the present review, we discuss the current consensus on the treatment of acute pancreatitis with protease inhibitors and also whether treatment with protease inhibitors decreases the morbidity and mortality rates resulting from acute pancreatitis.