Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden.
Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
J Intern Med. 2023 Aug;294(2):216-227. doi: 10.1111/joim.13673. Epub 2023 Jun 5.
Nonalcoholic fatty liver disease (NAFLD) is considered a multisystem disease, as it is bidirectionally linked to other cardiometabolic disorders, such as type 2 diabetes (T2D). However, the long-term risk for microvascular outcomes in NAFLD is unclear.
Using the outpatient part of the nationwide Swedish Patient Register in the time period between 01/01/2002 and 12/31/2019, we identified all individuals with a first NAFLD diagnosis (N = 6785) and matched these (age, sex, and municipality) with up to 10 reference individuals from the general population (N = 61,136). Using population-based registers, we ascertained the development of microvascular diseases. The primary outcome was defined as a composite outcome of any diagnosis representative of microvascular disease (chronic kidney disease, retinopathy, or neuropathy). As secondary outcomes, we separately examined the risk of each specific microvascular outcome. Hazard ratios (aHR, adjusted for cirrhosis and time-varying T2D, hypertension, and hyperlipidemia) for the outcomes were calculated by Cox proportional-hazards models.
Median follow-up was 5.7 years. The incidence rate of microvascular diseases was >twofold higher in patients with NAFLD (10.8 per 1000 person-years [95% confidence interval (CI) = 9.9-11.8]) versus reference individuals (4.7 per 1000 person-years [95%CI = 4.5-4.9]). NAFLD was independently and positively associated with the development of microvascular diseases compared to non-NAFLD subjects (aHR = 1.45 [95%CI = 1.28-1.63]). When stratifying the analysis by follow-up time, sex, or age categories, results remain virtually unchanged.
NAFLD is positively and independently associated with the development of microvascular diseases. The risk for development of microvascular diseases should be taken into account in the personalized risk assessment of individuals with NAFLD.
非酒精性脂肪性肝病（NAFLD）被认为是一种多系统疾病，因为它与其他心血管代谢疾病（如 2 型糖尿病（T2D））呈双向关联。然而，NAFLD 发生微血管并发症的长期风险尚不清楚。
我们使用全国性瑞典患者登记处的门诊部分，在 2002 年 1 月 1 日至 2019 年 12 月 31 日期间，确定了所有首次诊断为 NAFLD 的个体（N=6785），并将这些个体（年龄、性别和市）与来自普通人群的最多 10 名对照个体进行匹配（N=61136）。我们使用基于人群的登记处确定微血管疾病的发展情况。主要结局定义为任何代表微血管疾病的诊断的复合结局（慢性肾脏病、视网膜病变或神经病变）。作为次要结局，我们分别检查了每种特定微血管结局的风险。通过 Cox 比例风险模型计算结局的风险比（aHR，调整肝硬化和时变 T2D、高血压和高脂血症）。
中位随访时间为 5.7 年。与对照个体相比（1000 人年中发病率为 4.7[95%置信区间（CI）4.5-4.9]），NAFLD 患者微血管疾病的发病率高出两倍以上（1000 人年中发病率为 10.8[95%CI 9.9-11.8]）。与非 NAFLD 患者相比，NAFLD 独立且正向与微血管疾病的发展相关（aHR=1.45[95%CI 1.28-1.63]）。当按随访时间、性别或年龄类别对分析进行分层时，结果几乎保持不变。
NAFLD 与微血管疾病的发生呈正相关且独立相关。在对 NAFLD 患者进行个体化风险评估时，应考虑发生微血管疾病的风险。
