Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
Department of Gastroenterology, NHS Tayside, Ninewells Hospital and Medical School, Dundee, Scotland.
PLoS One. 2024 Apr 16;19(4):e0299507. doi: 10.1371/journal.pone.0299507. eCollection 2024.
BACKGROUND AND AIMS: Metabolic dysfunction associated steatotic liver disease (MASLD) increases the risk of incident chronic kidney disease (CKD). However, the relative risk of CKD associated with increasing hepatic fibrosis, and consequent mortality risk, remains underexplored in real-world cohorts. In this study, we sought to establish whether hepatic fibrosis is associated with increased CKD risk and explore differences in mortality risk in a cohort of people living with MASLD, contingent on liver fibrosis and CKD status. METHODS: This was an observational study of people who underwent routine liver function testing in Tayside, Scotland. MASLD was defined as: elevated ALT (>30 U/L) or GGT (>73 U/L); presence of diabetes, and/or hypertension, and/or obesity; weekly alcohol consumption <14 units (112g (+/-8g) alcohol); and negative screen for other aetiologies. Data was collected from digital health records. We used log-binomial models to quantify the risk of CKD among those with and without fibrosis, and Cox regression models to estimate differences in mortality risk dependent on fibrosis and CKD. RESULTS: In our cohort (n = 2,046), 1,448 (70.8%) people had MASLD without fibrosis and 598 (29.2%) with fibrosis; 161 (11.1%) and 117 (19.6%) respectively also had CKD. After excluding individuals with structural, autoimmune, or malignant CKD (n = 22), liver fibrosis (n = 593; 18.9% with CKD) was associated with increased CKD risk (aRR = 1.31, 1.04-1.64, p = 0.021). Increased mortality risk was observed for those with liver fibrosis (aHR = 2.30, 1.49-3.56, p = <0.001) and was higher again among people with both fibrosis and CKD (aHR = 5.07, 3.07-8.39, p = <0.014). CONCLUSIONS: Liver fibrosis was an independent risk factor for CKD in this cohort of people living with MASLD. Furthermore, those with MASLD with liver fibrosis had higher risk for mortality and this risk was further elevated among those with co-morbid CKD. Given the increased risk of CKD, and consequent mortality risk, among people living with MASLD fibrosis, renal function screening should be considered within liver health surveillance programmes and guidelines.
背景与目的：代谢功能障碍相关脂肪性肝病（MASLD）会增加慢性肾脏病（CKD）的发病风险。然而，在真实队列中，肝纤维化程度与 CKD 发病风险及死亡率之间的相关性尚未得到充分研究。本研究旨在探讨 MASLD 患者肝纤维化与 CKD 发病风险的关系，并进一步探索肝纤维化与 CKD 状态对患者死亡率风险的影响。
方法：本研究为苏格兰泰赛德地区进行常规肝功能检测的人群的观察性研究。MASLD 的定义为：丙氨酸氨基转移酶（ALT）>30 U/L 或γ-谷氨酰转移酶（GGT）>73 U/L；存在糖尿病、高血压和/或肥胖症；每周饮酒量<14 单位（112 克[+/-8 克]酒精）；且其他病因检测结果为阴性。数据来自电子健康记录。我们采用对数二项式模型量化无纤维化和有纤维化患者的 CKD 发病风险，采用 Cox 回归模型估计纤维化和 CKD 对死亡率风险的影响。
结果：在我们的队列（n=2046）中，1448 人（70.8%）患有无纤维化的 MASLD，598 人（29.2%）患有纤维化；分别有 161 人（11.1%）和 117 人（19.6%）患有 CKD。排除结构性、自身免疫性或恶性 CKD 个体（n=22）和有纤维化的个体（n=593；有 CKD 的占 18.9%）后，肝纤维化（n=593；有 CKD 的占 18.9%）与 CKD 发病风险增加相关（ARR=1.31，1.04-1.64，p=0.021）。有纤维化的患者死亡率风险增加（aHR=2.30，1.49-3.56，p<0.001），且纤维化合并 CKD 的患者死亡率风险更高（aHR=5.07，3.07-8.39，p=0.014）。
结论：在本队列中，肝纤维化是 MASLD 患者发生 CKD 的独立危险因素。此外，有肝纤维化的 MASLD 患者的死亡率风险更高，且合并 CKD 的患者死亡率风险进一步增加。鉴于 MASLD 患者纤维化与 CKD 发病风险及死亡率相关，在肝健康监测计划和指南中应考虑进行肾功能筛查。
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