Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain; SeLiver group, Instituto de Biomedicina de Sevilla, Spain; CIBERehd, Spain.
Hospital Clínico Universitario de Valladolid, Centro de Investigación de Endocrinología y Nutrición, Universidad de Valladolid, Spain.
J Hepatol. 2020 Jul;73(1):17-25. doi: 10.1016/j.jhep.2020.02.028. Epub 2020 Mar 6.
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) could play a catalytic role in the development of metabolic comorbidities, although the magnitude of this effect in metabolically healthy patients with NAFLD remains unclear. We assessed the role of biopsy-proven NAFLD on the risk of developing type 2 diabetes mellitus (T2DM) and other metabolic comorbidities (arterial hypertension [AHT], and dyslipidemia) in metabolically healthy patients.
We included 178 metabolically healthy-defined by the absence of baseline T2DM, AHT, dyslipidemia-patients with biopsy-proven NAFLD from the HEPAmet Registry (N = 1,030). Hepamet fibrosis score (HFS), NAFLD fibrosis score, and Fibrosis-4 were calculated. Follow-up was computed from biopsy to the diagnosis of T2DM, AHT, or dyslipidemia.
During a follow-up of 5.6 ± 4.4 years, T2DM occurred in 9% (16/178), AHT in 8.4% (15/178), low HDL in 9.6% (17/178), and hypertriglyceridemia in 23.6% (42/178) of patients. In multivariate analysis, significant fibrosis predicted T2DM and AHT. Independent variables related to T2DM appearance were significant fibrosis (HR 2.95; 95% CI 1.19-7.31; p = 0.019), glucose levels (p = 0.008), age (p = 0.007) and BMI (p = 0.039). AHT was independently linked to significant fibrosis (HR 2.39; 95% CI 1.14-5.10; p = 0.028), age (p = 0.0001), BMI (p = 0.006), glucose (p = 0.021) and platelets (p = 0.050). The annual incidence rate of T2DM was higher in patients with significant fibrosis (4.4 vs. 1.2 cases per 100 person-years), and increased in the presence of obesity, similar to AHT (4.6 vs. 1.1 cases per 100 person-years). HFS >0.12 predicted the risk of T2DM (25% [4/16] vs. HFS <0.12 4.5% [4/88]; logRank 6.658, p = 0.010).
Metabolically healthy patients with NAFLD-related significant fibrosis were at greater risk of developing T2DM and AHT. HFS >0.12, but not NAFLD fibrosis score or Fibrosis-4, predicted the occurrence of T2DM.
Patients with biopsy-proven non-alcoholic fatty liver disease and significant fibrosis were at risk of developing type 2 diabetes mellitus and arterial hypertension. The risk of metabolic outcomes in patients with significant fibrosis was increased in the presence of obesity. In addition to liver biopsy, patients at intermediate-to-high risk of significant fibrosis by Hepamet fibrosis score were at risk of type 2 diabetes mellitus.
非酒精性脂肪性肝病（NAFLD）可能在代谢合并症的发展中发挥催化作用，尽管代谢健康的 NAFLD 患者中这种影响的程度尚不清楚。我们评估了经活检证实的 NAFLD 在代谢健康的患者中发生 2 型糖尿病（T2DM）和其他代谢合并症（动脉高血压[AHT]和血脂异常）的风险中的作用。
我们纳入了 178 名代谢健康的患者（定义为基线时无 T2DM、AHT、血脂异常），这些患者来自 HEPAmet 登记处的经活检证实的 NAFLD 患者（N=1030）。计算 Hepamet 纤维化评分（HFS）、NAFLD 纤维化评分和 Fibrosis-4。随访时间从活检开始到 T2DM、AHT 或血脂异常的诊断。
在 5.6±4.4 年的随访期间，178 名患者中有 9%（16/178）发生了 T2DM，8.4%（15/178）发生了 AHT，9.6%（17/178）发生了低 HDL，23.6%（42/178）发生了高甘油三酯血症。多变量分析显示，显著纤维化预测了 T2DM 和 AHT。与 T2DM 发生相关的独立变量包括显著纤维化（HR 2.95；95%CI 1.19-7.31；p=0.019）、血糖水平（p=0.008）、年龄（p=0.007）和 BMI（p=0.039）。AHT 与显著纤维化（HR 2.39；95%CI 1.14-5.10；p=0.028）、年龄（p=0.0001）、BMI（p=0.006）、血糖（p=0.021）和血小板（p=0.050）相关。有显著纤维化的患者 T2DM 的年发生率更高（4.4 例/100 人年 vs. 1.2 例/100 人年），且肥胖患者的发生率更高，与 AHT 相似（4.6 例/100 人年 vs. 1.1 例/100 人年）。HFS>0.12 预测了 T2DM 的风险（25%[4/16] vs. HFS<0.12 4.5%[4/88]；logRank 6.658，p=0.010）。
与 NAFLD 相关的显著纤维化的代谢健康患者发生 T2DM 和 AHT 的风险增加。HFS>0.12 但不是 NAFLD 纤维化评分或 Fibrosis-4 预测了 T2DM 的发生。
有活检证实的非酒精性脂肪性肝病和显著纤维化的患者有发生 2 型糖尿病和动脉高血压的风险。在肥胖患者中，显著纤维化患者发生代谢结果的风险增加。除了肝活检外，Hepamet 纤维化评分中处于中至高显著纤维化风险的患者也有发生 2 型糖尿病的风险。
