General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, 610041, China.
Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
BMC Med. 2023 Oct 20;21(1):398. doi: 10.1186/s12916-023-03080-6.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification.
After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections.
Participants aged 59 (51-64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid-base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results.
Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD.
代谢相关脂肪性肝病（MAFLD）是一种新定义的疾病，包含肝脂肪变性和代谢功能障碍。然而，MAFLD 与多系统疾病的关系尚不清楚，这些疾病的时间依赖性顺序尚需进一步阐明。
在倾向评分匹配后，纳入英国生物库社区研究中的 163303 例 MAFLD 患者和 163303 例匹配患者。采用国际疾病分类，第十次修订版（ICD-10）将医疗条件重新分类为 490 种和 16 种特定死因。我们进行了疾病轨迹分析，以绘制将 MAFLD 与各种健康状况联系起来的关键途径，概述它们的相互关系。
本研究纳入了年龄为 59（51-64）岁、主要为男性（62.5%）的参与者。在 12.9 年的随访期间，通过使用 Cox 回归模型进行表型全基因组关联分析，发现 MAFLD 患者发生 113 种医疗条件和 8 种死因的风险更高。使用疾病配对建立 MAFLD 的时间疾病轨迹，揭示了哮喘、糖尿病、高血压、甲状腺功能减退症、烟草滥用、憩室病、慢性缺血性心脏病、肥胖、良性肿瘤和炎症性关节炎等中间疾病。这些轨迹主要导致急性心肌梗死、体液、电解质和酸碱平衡紊乱、传染性胃肠炎和结肠炎以及功能性肠病。关于 MAFLD 的死亡轨迹，恶性肿瘤、心血管疾病和呼吸系统死亡是主要原因，器官衰竭、传染病和内环境紊乱是主要终末期情况。基于 MAFLD 遗传易感性水平的疾病轨迹分析得出了一致的结果。
MAFLD 患者存在多种不同的医疗条件和死因风险。值得注意的是，这些疾病和潜在死因构成了许多途径，可能是预防 MAFLD 患者整体健康状况下降的有希望的靶点。
