Can we expect progress in the treatment of fibrosis in the course of chronic pancreatitis?

ABSTRACTChronic pancreatitis (CP) is a necroinflammatory process characterized by loss of both exocrine and endocrine function. To date, the disease has been treated symptomatically. Real advances in CP management can be expected once the pathophysiology of the disease is elucidated and individual stages of its development are properly managed. A key role in the CP pathogenesis is played by activation of pancreatic stellate cells (PSCs) that cooperate with the remaining pancreatic cells. All these cells produce cytokines, growth factors, angiotensin and other substances, which paracrinally or autocrinally induce further, persistent activation of PSCs. The activated PSCs are capable of producing and modifying the extracellular matrix. An optimal therapeutic preparation should exert beneficial effects on all the above-mentioned phenomena observed in CP. The most promising treatment modalities include blocking of the renin-angiotensin system (RAS), activation of peroxisome proliferator-activated receptors gamma (PPAR-γ), influence on the remaining PSC signaling pathways, blocking of substances produced by activated PSCs, and antioxidants. The findings of many recent experimental studies are highly encouraging; however, their efficacy should be confirmed in well-designed clinical trials.