Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida.
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
Clin Gastroenterol Hepatol. 2021 Feb;19(2):349-357. doi: 10.1016/j.cgh.2020.03.047. Epub 2020 Mar 30.
BACKGROUND & AIMS: Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early onset ICP (EO-ICP; median age, 19.2 y) and late-onset ICP (LO-ICP; median age, 56.2 y). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, and ACP.
We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal-Wallis test was used to compare continuous variables across groups and based on genetic variants.
Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P = .04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P = .001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P = .001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP.
We confirmed previously reported ages at onset of symptoms for EO-ICP and LO-ICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared with approximately one quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.
特发性慢性胰腺炎（ICP）是 CP 的第二大亚型。1994 年，研究人员报告了 ICP 症状发病年龄的双峰模式：早发性 ICP（EO-ICP；中位年龄 19.2 岁）和迟发性 ICP（LO-ICP；中位年龄 56.2 岁）。ICP 的发病年龄和临床特征与酒精相关性 CP（ACP）不同。然而，PRSS1 中的变异尚未与 ICP 相关。我们在一个大型的北美患者队列中重新检查了 ICP 的发病年龄，并研究了遗传因素和酒精使用对 EO-ICP、LO-ICP 和 ACP 患者的影响。
我们对参加北美胰腺炎研究 2 的欧洲血统的 CP 患者进行了横断面分析，这是一项对 2000 年 8 月至 2014 年 12 月美国 26 个中心的 1195 例 CP 患者进行的前瞻性研究。我们比较了 130 例终生戒酒的 CP 患者（61 例早发和 69 例晚发）、308 例轻至中度饮酒者和 225 例 ACP 且大量饮酒者的症状发病年龄。对来自可用患者的 DNA 进行了与 SPINK1、CFTR 和 CTRC 相关的 CP 变异分析。Kruskal-Wallis 检验用于比较各组和基于遗传变异的连续变量。
EO-ICP 且无酒精使用的患者症状发病年龄的中位数为 20 岁，LO-ICP 且无酒精使用的患者症状发病年龄的中位数为 58 岁，轻至中度饮酒者 CP 的患者症状发病年龄的中位数为 47 岁，ACP 的患者症状发病年龄的中位数为 44 岁。与 LO-ICP 患者（31%）相比，EO-ICP 患者中更常见持续性疼痛（65%）（P=0.04）。与 EO-ICP 患者（11%）相比，ACP 患者中更常见假性囊肿（43%）（P=0.001）。与 LO-ICP 患者（23%）、轻至中度饮酒者 CP（26%）或 ACP（23%）相比，EO-ICP 患者更常见 SPINK1、CFTR 或 CTRC 的致病性变异（49%）（P=0.001）。在 SPINK1 变异的患者中，EO-ICP 的症状发病年龄中位数为 12 岁，轻至中度饮酒者 CP 的症状发病年龄中位数为 24 岁。在 CFTR 变异的患者中，轻至中度饮酒者的症状发病年龄为 41 岁，但这种变异并未影响 EO-ICP 或 ACP 的发病年龄。
我们在一个北美队列中证实了先前报告的 EO-ICP 和 LO-ICP 的症状发病年龄。我们发现 EO-ICP、LO-ICP 和 ACP 患者的临床特征存在差异。与 LO-CP 或 ACP 的患者相比，几乎一半的 EO-ICP 患者有与 CP 相关的遗传变异，而大约四分之一的 LO-CP 或 ACP 患者有遗传变异。遗传变异影响某些组的症状发病年龄。
