[Chronic pancreatitis: beyond alcohol]

For many years, the classification of chronic pancreatitis has been oversimplified according to whether the cause is alcoholic (60-70% of cases according to published series) or non-alcoholic (20-40% of the remaining cases). Recognition of smoking as an important risk factor and increasing identification of factors of genetic susceptibility have placed these percentages in doubt and have led to a reconceptualization of the disease as a multifactorial process. Mutations in the PRSS1, SPINK1 and CFTR genes have been confirmed as major risk factors, while mutations in the CTRC and CASR genes are considered lesser risk factors for the development of chronic pancreatitis. These genetic variants are expressed in a much higher percentage of patients with chronic pancreatitis than could be expected by chance. The trans-heterozygous combination multiplies the risk of chronic pancreatitis and demonstrates the degree of complexity of the etiopathogenic mechanisms of the disease. Ductal obstruction and autoimmunity are other important etiologic factors of chronic pancreatitis that need a specific review. The present article reviews the latest studies evaluating the role of alcohol and smoking in chronic pancreatitis and the most significant genetic factors.