非酒精性脂肪肝疾病和肝纤维化对慢性肾脏病患者不良临床结局和死亡率的影响：利用英国生物库的前瞻性队列研究。
The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.
机构信息
Department of Cardiovascular and Metabolic Medicine, 3Rd Floor Clinical Sciences Centre, Institute of Life Course and Medical Sciences, Liverpool University Hospitals NHS Foundation Trust, University of Liverpool, Longmoor Lane, Liverpool, L9 7AL, UK.
University Hospital Aintree, Liverpool University Hospital NHS Foundation Trust, Liverpool, L9 7AL, UK.
出版信息
BMC Med. 2023 May 18;21(1):185. doi: 10.1186/s12916-023-02891-x.
BACKGROUND
Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD.
METHODS
A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) associated with having NAFLD (elevated hepatic steatosis index or ICD-code) and NAFLD fibrosis (elevated fibrosis-4 (FIB-4) score or NAFLD fibrosis score (NFS)) on cardiovascular events (CVE), progression to end-stage renal disease (ESRD) and all-cause mortality.
RESULTS
56.2% of individuals with CKD had NAFLD at baseline, and 3.0% and 7.7% had NAFLD fibrosis according to a FIB-4 > 2.67 and NFS ≥ 0.676, respectively. The median follow-up was 13 years. In univariate analysis, NAFLD was associated with an increased risk of CVE (HR 1.49 [1.38-1.60]), all-cause mortality (HR 1.22 [1.14-1.31]) and ESRD (HR 1.26 [1.02-1.54]). Following multivariable adjustment, NAFLD remained an independent risk factor for CVE overall (HR 1.20 [1.11-1.30], p < 0.0001), but not ACM or ESRD. In univariate analysis, elevated NFS and FIB-4 scores were associated with increased risk of CVE (HR 2.42 [2.09-2.80] and 1.64 [1.30-2.08]) and all-cause mortality (HR 2.82 [2.48-3.21] and 1.82 [1.47-2.24]); the NFS score was also associated with ESRD (HR 5.15 [3.52-7.52]). Following full adjustment, the NFS remained associated with an increased incidence of CVE (HR 1.19 [1.01-1.40]) and all-cause mortality (HR 1.31 [1.13-1.52]).
CONCLUSIONS
In people with CKD, NAFLD is associated with an increased risk of CVE, and the NAFLD fibrosis score is associated with an elevated risk of CVE and worse survival.
背景
慢性肾脏病（CKD）和非酒精性脂肪性肝病（NAFLD）常同时存在。我们评估了 NAFLD 对 CKD 患者不良临床结局和全因死亡率的影响。
方法
共纳入 18073 名英国生物库参与者，他们被确定患有 CKD（eGFR<60ml/min/1.73m 或白蛋白尿>3mg/mmol），通过电子链接对其进行前瞻性随访，以获取医院和死亡记录。Cox 回归估计了患有 NAFLD（肝脂肪变性指数升高或 ICD 编码）和 NAFLD 纤维化（纤维化-4 评分升高或 NAFLD 纤维化评分升高）与心血管事件（CVE）、进展为终末期肾病（ESRD）和全因死亡率相关的风险比（HR）。
结果
基线时，56.2%的 CKD 患者存在 NAFLD，根据纤维化-4>2.67 和 NAFLD 纤维化评分≥0.676，分别有 3.0%和 7.7%的患者存在 NAFLD 纤维化。中位随访时间为 13 年。单因素分析显示，NAFLD 与 CVE 风险增加相关（HR 1.49[1.38-1.60]）、全因死亡率（HR 1.22[1.14-1.31]）和 ESRD（HR 1.26[1.02-1.54]）。多变量调整后，NAFLD 仍然是总体 CVE 的独立危险因素（HR 1.20[1.11-1.30]，p<0.0001），但不是 ACM 或 ESRD 的危险因素。单因素分析显示，升高的 NFS 和 FIB-4 评分与 CVE（HR 2.42[2.09-2.80]和 1.64[1.30-2.08]）和全因死亡率（HR 2.82[2.48-3.21]和 1.82[1.47-2.24]）风险增加相关；NFS 评分也与 ESRD 相关（HR 5.15[3.52-7.52]）。在完全调整后，NFS 与 CVE 发生率增加（HR 1.19[1.01-1.40]）和全因死亡率增加（HR 1.31[1.13-1.52]）仍相关。
结论
在 CKD 患者中，NAFLD 与 CVE 风险增加相关，而 NAFLD 纤维化评分与 CVE 风险增加和生存预后较差相关。
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