目的:原发性胆汁性胆管炎(PBC)是一种慢性,免疫介导的肝病,可导致纤维化和肝硬化。在这项队列研究中,我们旨在调查英国人群队列中PBC的发病率和死亡率以及代谢组学变化.
方法:454名参与者的PBC和908名倾向得分(年龄,性别,BMI,种族)匹配的无肝病对照纳入研究。分析了PBC参与者和对照组的代谢组学概况。Further,通过PheWAS分析研究了PBC相关的合并症。最后,我们使用精细和灰色竞争风险回归模型评估了PBC患者的死亡原因.
结果:与对照组相比,与氨基酸代谢相关的各种途径,脂质,肝脏生化在PBC个体中显著富集。我们发现PBC患者的S-HDL-胆固醇和糖蛋白乙酰水平降低,并且与循环系统疾病有关。值得注意的是,PBC个体的消化系统疾病患病率较高,自身免疫性疾病,心血管疾病,贫血,精神障碍,与对照组相比,尿路感染。引人注目的是,与对照组相比,PBC组的总死亡率几乎高出三倍,消化系统疾病导致死亡率显著上升。随后的分析,通过包括APRI评分的倾向评分匹配来增强,证明观察到的发病率不能完全归因于晚期肝病。
结论:我们的研究为PBC患者的发病率提供了详细的视角。对疾病状态对发病率的潜在影响的探索表明,PBC的早期发现和早期治疗可以改善患者的预后并预防合并症的发作。最后,代谢组学改变可以代表PBC发育的病理生理过程之间的联系,programming,和相关的发病率。
OBJECTIVE: Primary biliary cholangitis (PBC) is a chronic, immune-mediated liver disease that can lead to fibrosis and cirrhosis. In this cohort
study, we aimed to investigate morbidity and mortality in conjunction with metabolomic changes of PBC in a UK population-based cohort.
METHODS: 454 participants with PBC and 908 propensity score (age, sex, BMI, ethnicity) matched controls without liver disease were included in the
study. A subset of participants with PBC and controls were analysed for their metabolomic profile. Further, PBC-associated comorbidities were investigated by PheWAS analysis. Lastly, we assessed causes of death in individuals with PBC using a Fine and Grey competing-risks regression model.
RESULTS: Compared to the control group, various pathways associated with the metabolism of amino acids, lipids, and liver biochemistry were significantly enriched in individuals with PBC. We found reduced levels of S-
HDL-cholesterol and Glycoprotein Acetyls in individuals with PBC as well as an association with diseases of the circulatory system. Notably, PBC individuals had a higher prevalence of digestive diseases, autoimmune diseases, cardiovascular diseases, anaemias, mental disorders, and urinary tract infections compared to the control group. Strikingly, the overall mortality was almost three times higher in the PBC group compared to the control group, with diseases of the digestive system accounting for a significant elevation of the death rate. A subsequent analysis, enhanced by propensity score matching that included the APRI score, demonstrated that the observed morbidity could not be exclusively attributed to advanced hepatic disease.
CONCLUSIONS: Our
study provides a detailed perspective on the morbidity of individuals with PBC. The exploration of potential effects of disease state on morbidity suggest that early detection and early treatment of PBC could enhance patient prognosis and prevent the onset of comorbid diseases. Finally, the metabolomic alterations could represent a link between the pathophysiological processes underlying PBC development, progression, and associated morbidity.