自身免疫性肝病与慢性乙型肝炎的相关性：欧洲人群多变量孟德尔随机化研究。

Association between autoimmune liver diseases and chronic hepatitis B: A multivariable Mendelian randomization study in European population.

机构信息

Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China.

出版信息

Prev Med. 2024 Jul;184:107984. doi: 10.1016/j.ypmed.2024.107984. Epub 2024 May 3.

DOI:10.1016/j.ypmed.2024.107984

PMID:38705484

Abstract

BACKGROUND

Observational studies have indicated a link between autoimmune liver diseases (AILD) and chronic hepatitis B (CHB) through observational studies. The association between AILD and CHB remains indeterminate.

METHODS

A two-sample Mendelian randomization (MR) analysis was conducted to scrutinize the causal nexus between AILD and CHB utilizing summary statistics derived from extensive genome-wide association studies (GWASs) in European populations. The primary statistical methodology employed was the inverse variance-weighted (IVW) method to deduce the causal connection of AILD on CHB. This study incorporated primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) as subtypes of AILD. Additionally, we conducted a multivariable MR (MVMR) analysis to account for the potential confounding effects of smoking, alcohol consumption, body mass index (BMI), and some autoimmune diseases.

RESULTS

Our MR investigation encompassed a cohort of 725,816 individuals. The MR analysis revealed that genetically predicted PSC significantly correlated with a reduced risk of CHB (IVW OR = 0.857; 95%CI: 0.770-0.953, P = 0.005). Conversely, the reverse MR analysis suggested that genetic susceptibility to PSC might not modify the risk of CHB (IVW OR = 1.004; 95% CI: 0.958-1.053, P = 0.866). Genetically proxied PBC and AIH exhibited no discernible causal association with CHB in the MR analysis using the IVW method (P = 0.583; P = 0.425). The MVMR analysis still indicated a decreased risk of CHB associated with PSC (OR = 0.853, P = 0.003).

CONCLUSION

Our study elucidates a causal relationship between PSC and a diminished risk of CHB.

摘要

背景

观察性研究通过观察性研究表明自身免疫性肝病（AILD）和慢性乙型肝炎（CHB）之间存在关联。 AILD 和 CHB 之间的关联仍然不确定。

方法

使用来自欧洲人群的全基因组关联研究（GWAS）的汇总统计信息，进行两样本 Mendelian 随机化（MR）分析，以仔细研究 AILD 和 CHB 之间的因果关系。主要统计方法是逆方差加权（IVW）方法，以推断 AILD 对 CHB 的因果关系。本研究将原发性胆汁性胆管炎（PBC）、原发性硬化性胆管炎（PSC）和自身免疫性肝炎（AIH）作为 AILD 的亚型。此外，我们进行了多变量 MR（MVMR）分析，以考虑吸烟，饮酒，体重指数（BMI）和某些自身免疫性疾病的潜在混杂影响。

结果

我们的 MR 研究包括 725816 个人的队列。 MR 分析表明，遗传预测的 PSC 与 CHB 的风险降低显着相关（IVW OR = 0.857; 95％CI：0.770-0.953，P = 0.005）。相反，反向 MR 分析表明，PSC 的遗传易感性可能不会改变 CHB 的风险（IVW OR = 1.004; 95％CI：0.958-1.053，P = 0.866）。使用 IVW 方法进行 MR 分析时，遗传上接近的 PBC 和 AIH 与 CHB 之间没有明显的因果关系（P = 0.583; P = 0.425）。 MVMR 分析仍表明与 PSC 相关的 CHB 风险降低（OR = 0.853，P = 0.003）。