High clinical and genetic similarity between chronic pancreatitis associated with light-to-moderate alcohol consumption and classical alcoholic chronic pancreatitis

Background & Aims Heavy alcohol consumption and genetic factors represent the two major etiologies of chronic pancreatitis (CP). However, little is so far known about the clinical features and genetic basis of light-to-moderate alcohol consumption-related CP (LMA-CP). Methods A cross-sectional analysis was performed upon 1061 Chinese CP patients between 2010 and 2015. CP was classified as classical alcoholic CP (ACP; n=206), LMA-CP (n=154), and idiopathic CP (ICP; n=701). Clinical features and genetic characteristics (PRSS1, SPINK1, CTRC, CFTR variant status) were compared between the different groups. Odds ratios (OR) with 95% confidence intervals were calculated to ascertain the combinatorial effect of alcohol consumption and gene mutation. Results Compared with ICP, the clinical features of LMA-CP were characterized by higher rates of developing pancreatic stones, pseudocyst, diabetes, and steatorrhea, which were similar to those associated with ACP. The prevalence of CP-related gene variants in LMA-CP was 38.3%, similar to ACP (39.8%), although significantly lower than ICP (56.2%). Alcohol consumption enhanced the risk of a poor clinical outcome whilst genetic factors amplified alcohol’s effects. Compared to ICP, LMA-CP and ACP were associated with a high risk of pancreatic stones (patients-without-variants, OR=2.01 and 2.54; patients-with-variants, OR=2.17 and 1.07), pseudocyst (patients-without-variants, OR=1.03 and 1.43; patients-with-variants, OR=1.67 and 2.14), diabetes mellitus (patients-without-variants, OR=0.86 and 1.31; patients-with-variants, OR=2.05 and 1.55) and steatorrhea (patients-without-variants, OR=1.56 and 2.10; patients-with-variants, OR=2.11 and 1.60). Conclusions Evidence was presented to show that LMA-CP was clinically and genetically similar to ACP but significantly different from ICP. Our findings provide support to the growing view that there is no safe level of alcohol consumption