Etiology and Risk Factors of Acute and Chronic Pancreatitis

Abstract

Based on the recognition of common etiological and genetic risk factors, acute and chronic pancreatitis are increasingly regarded as a continuum of the same disease, with a significant overlap of clinical manifestations and phenotypes but distinct morphological and imaging appearances. Recent population-based and cohort studies have found that tobacco smoke conveys a greater risk than immoderate alcohol consumption for the development of chronic pancreatitis, and hypertriglyceridemia has been identified as a risk factor for acute pancreatitis - even when plasma levels are only mildly elevated. Hereditary pancreatitis, in its autosomal dominant form, is associated with mutations in the cationic trypsinogen gene (PRSS1), whereas a number of germline variations in other genes have been found to represent risk factors for chronic as well as acute pancreatitis. For now, most of these involve the pancreatic digestive protease/antiprotease system. Oftentimes, affected patients are burdened with multiple or accumulating risk factors, and genetic traits when combined with environmental toxins compound the chance of developing the disease. Determining the underlying etiology of pancreatitis is worth the effort since formerly intractable varieties such as autoimmune pancreatitis are now becoming increasingly treatable, and subtype-specific therapeutic modalities may become available.

Keywords: Alcohol abuse; Etiologic factors; Genetic risk; Pancreatitis.

Fig. 1

Pancreatitis-associated genetic risk factors (sequence variants) influence activation, auto-activation, inhibition, or degradation processes of proteases and change the protease/anti-protease equilibrium in pancreatic acinar cells.

Fig. 2

A CT scan of patient with SPINK1-p.N34S/CTRC-p.G60G mutation. Note enlargement of the head of the pancreas and multiple calcifications. B CT scan of patient with autoimmune pancreatitis type 1 (IgG4 related) with a homogenous (sausage-shaped) enlargement of the entire gland and an enhanced rim.