Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
School of Public Health, Zhejiang University School of Medicine, Hangzhou, China; Centre for Global Health, Usher Institute, the University of Edinburgh, Edinburgh, UK.
Med. 2024 Nov 8;5(11):1413-1423.e3. doi: 10.1016/j.medj.2024.07.013. Epub 2024 Aug 7.
The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing, but its subsequent health consequences have not been thoroughly examined.
A phenome-wide association study was conducted to map the associations of MASLD with 948 unique clinical outcomes among 361,021 Europeans in the UK Biobank. Disease trajectory and comorbidity analyses were applied to visualize the sequential patterns of multiple comorbidities related to the occurrence of MASLD. The associations jointly verified by observational and polygenic phenome-wide analyses were further replicated by two-sample Mendelian randomization analysis using data from the FinnGen study and international consortia.
The observational and polygenic phenome-wide association study revealed the associations of MASLD with 96 intrahepatic and extrahepatic diseases, including circulatory, metabolic, genitourinary, neurological, gastrointestinal, and hematologic diseases. Sequential patterns of MASLD-related extrahepatic comorbidities were primarily found in circulatory, metabolic, and inflammatory diseases. Mendelian randomization analyses supported the causal associations between MASLD and the risk of several intrahepatic disorders, metabolic diseases, cardio-cerebrovascular disease, and ascites but found no associations with neurological diseases.
This study elucidated multisystem comorbidities and health consequences of MASLD, contributing to the development of combination interventions targeting distinct pathways for health promotion among patients with MASLD.
X.L. was funded by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (82204019) and Y.D. was funded by the Key Project of Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province (GZY-ZJ-KJ-24077) and the National Natural Science Foundation of China (82001673 and 82272860).
代谢功能障碍相关脂肪性肝病（MASLD）的全球负担正在增加，但尚未对其随后的健康后果进行全面研究。
我们进行了一项全表型关联研究，以在英国生物库中 361021 名欧洲人中，对 MASLD 与 948 种独特临床结局之间的关联进行定位。疾病轨迹和合并症分析用于可视化与 MASLD 发生相关的多种合并症的序贯模式。通过观察性和多基因全表型关联分析联合验证的关联，使用 FinnGen 研究和国际联盟的数据，通过两样本孟德尔随机化分析进一步复制。
观察性和多基因全表型关联研究揭示了 MASLD 与 96 种肝内和肝外疾病之间的关联，包括循环、代谢、泌尿生殖、神经、胃肠道和血液疾病。MASLD 相关肝外合并症的序贯模式主要发生在循环、代谢和炎症性疾病中。孟德尔随机化分析支持 MASLD 与几种肝内疾病、代谢疾病、心脑血管疾病和腹水风险之间的因果关联，但未发现与神经疾病的关联。
这项研究阐明了 MASLD 的多系统合并症和健康后果，有助于为 MASLD 患者制定针对不同途径的联合干预措施，以促进健康。
X.L. 得到了浙江省杰出青年自然科学基金（LR22H260001）和国家自然科学基金（82204019）的资助，Y.D. 得到了浙江省中医药科技计划重点项目（GZY-ZJ-KJ-24077）和国家自然科学基金（82001673 和 82272860）的资助。
