酒精性胰腺炎的全球与中国疾病负担及酒精摄入的因果关联研究

Global and Chinese disease burden of alcoholic pancreatitis and its causal association with alcohol consumption

摘要:

背景与目的 酒精摄入是胰腺炎的重要可干预危险因素，但其在全球及中国酒精性胰腺炎疾病负担长期变化中的作用，以及其与急性与慢性胰腺炎的因果关联仍缺乏系统整合证据。本研究基于全球疾病负担（GBD）2021数据库，采用双样本孟德尔随机化（MR）方法，综合评估全球及中国酒精性胰腺炎的疾病负担特征、变化趋势及其潜在因果关系。方法 提取GBD 2021数据库中1990—2021年全球及中国酒精性胰腺炎的死亡数、死亡和失能调整生命年（DALY）数及其年龄标化率，按性别与年龄分层分析趋势，采用Joinpoint回归计算平均年度变化百分比，分解分析评估人口增长、老龄化及流行病学变化的贡献，并基于贝叶斯年龄-时期-队列（BAPC）模型预测至2040年疾病负担变化。同时利用公开GWAS汇总数据开展双样本MR分析，评估酒精摄入与急性及慢性胰腺炎的因果关联。结果 1990—2021年，全球及中国酒精性胰腺炎死亡数和DALY数持续上升，而年龄标化死亡率及年龄标化DALY率总体呈下降或稳定趋势，中国整体低于全球平均水平。男性及中老年人群负担显著更高。分解分析显示，疾病负担增加主要由人口增长及老龄化驱动，流行病学变化呈负向贡献。预测结果显示，未来年龄标化负担将缓慢下降，但绝对负担仍维持在较高水平。MR分析表明，遗传预测的酒精摄入增加与急性及慢性胰腺炎风险升高均存在稳定的正向因果关联。结论 全球及中国酒精性胰腺炎呈现“绝对负担上升、年龄标化负担下降”的特征，并存在明显性别与年龄差异。遗传学证据支持酒精摄入与胰腺炎风险之间的正向因果关系。加强控酒政策与高危人群干预，对于降低其长期疾病及社会经济负担具有重要意义。

Abstract:

Background and Aims Alcohol consumption is a major modifiable risk factor for pancreatitis. However, comprehensive evidence integrating the long-term disease burden of alcoholic pancreatitis and its causal relationship with acute and chronic pancreatitis remains limited. This study aimed to systematically evaluate the temporal trends, disease burden, and potential causal associations of alcoholic pancreatitis globally and in China using the Global Burden of Disease (GBD) 2021 database and two-sample Mendelian randomization (MR).Methods Data on deaths, disability-adjusted life years (DALYs), and corresponding age-standardized rates from 1990 to 2021 were extracted from the GBD 2021 database. Temporal trends were analyzed by sex and age group. Joinpoint regression was used to estimate the average annual percent change (AAPC), and decomposition analysis quantified the contributions of population growth, population aging, and epidemiological changes. A Bayesian age-period-cohort (BAPC) model was applied to project trends through 2040. Additionally, two-sample MR analysis based on publicly available GWAS summary statistics was conducted to assess the causal associations between alcohol consumption and pancreatitis.Results From 1990 to 2021, the numbers of deaths and DALYs attributable to alcoholic pancreatitis increased steadily both globally and in China, whereas age-standardized mortality and DALY rates declined or remained stable, with lower levels observed in China than the global average. The disease burden was substantially higher in males and older populations. Decomposition analysis indicated that population growth and aging were the primary drivers of the increased burden, while epidemiological changes contributed negatively. Projections suggested a continued slight decline in age-standardized burden, although the absolute burden will remain high. MR analysis demonstrated a robust positive causal association between genetically predicted alcohol consumption and increased risks of both acute and chronic pancreatitis.Conclusion Alcoholic pancreatitis exhibits a pattern of increasing absolute burden but declining age-standardized burden globally and in China, with marked age and sex disparities. Genetic evidence supports a positive causal relationship between alcohol consumption and pancreatitis risk. Strengthening alcohol control policies and targeted interventions is essential to reduce the long-term health and socioeconomic burden.