There are significant differences in the clinical features of early, late, and alcohol-related idiopathic chronic pancreatitis, with a potential genetic etiology in patients with early-onset idiopathic chronic pancreatitis (EO-ICP). This is according to study results published in Clinical Gastroenterology and Hepatology.

In this cross-sectional cohort study, researchers utilized the North American Pancreatitis Study 2 (NAPS2) to select patients with chronic pancreatitis (CP) who were of European ancestry (N=663). Patients who self-identified as lifetime abstainers of alcohol were divided by age of pancreatitis onset. Patients aged ≤35 years were classified as EO-ICP (n=61), and patients aged >35 years were classified as late-onset ICP (LO-ICP, n=69). Patients who reported alcohol consumption were classified based on number of drinks consumed: ≤4 drinks per day (light-to-moderate drinkers, n=308) or >4 drinks per day (heavy drinkers, n=225). Analysis for genetic mutations in PRSS1, CFTR, SPINK1, and CTRC genes was performed in all patients.

Approximately 50% of patients with EO-ICP carried a pathogenic gene variant associated with CFTR, SPINK1, and/or CTRC (n=30), compared to 23% of patients with LO-ICP (n=16). When compared with patients who were light-to-moderate drinkers with CP, the presence of genetic mutations accelerated clinical presentation with earlier onset of symptoms. The onset of symptoms in the EO-ICP group was significantly accelerated by the presence of a SPINK1 mutation, decreasing age of onset from 22 years to 12 years (P =.004). In light-to-moderate drinkers, this mutation accelerated the onset of symptoms from 50 years to 24 years (P <.001). A CFTR mutation accelerated the age of onset of symptoms in light-to-moderate drinkers with CP from 50 years to 41 years (P =.03).

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The researchers note that the study is limited by its cross-sectional design, which prevented them from conducting a longitudinal follow-up with patients. Important long-term clinical outcomes, like endocrine and exocrine insufficiency, also could not be determined.

According to researchers, novel insights into the etiopathogenesis of CP are provided by these findings. In addition to confirming the existence of 2 types of ICP (EO-ICP and LO-ICP), the researchers also found evidence suggesting the possibility of a gene-environment interaction between genetic variants and alcohol consumption. Future studies should utilize more advanced genetic analysis to better characterize the long-term course of these patients.

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Lewis MD, Talluri J, Wilcox CM, et al. Differences in age at onset of symptoms, and effects of genetic variants, in patients with early- vs late-onset idiopathic chronic pancreatitis in a North American cohort [published online March 30, 2020]. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2020.03.047