Di Ciaula Agostino, Shanmugam Harshitha, Ribeiro Rogério, Pina Ana, Andrade Rita, Bonfrate Leonilde, Raposo João F, Macedo M Paula, Portincasa Piero
Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Medical School, Piazza Giulio Cesare 11, Bari 70124, Italy.
Portuguese Diabetes Association-Education and Research Center (APDP-ERC), Lisbon 1150-082, Portugal.
Eur J Intern Med. 2023 Jan;107:52-59. doi: 10.1016/j.ejim.2022.10.024. Epub 2022 Nov 4.
In Non-Alcoholic Fatty Liver Disease (NAFLD), events driving early hepatic dysfunction with respect to specific metabolic pathways are still poorly known.
We enrolled 84 subjects with obesity and/or type 2 diabetes (T2D). FibroScan® served to assess NAFLD by controlled attenuation parameter (CAP), and fibrosis by liver stiffness (LS). Patients with LS above 7 kPa were excluded. APRI and FIB-4 were used as additional serum biomarkers of fibrosis. The stable-isotope dynamic breath test was used to assess the hepatic efficiency of portal extraction (as DOB) and microsomal metabolization (as cPDR) of orally-administered (C)-methacetin.
NAFLD occurred in 45%, 65.9%, and 91.3% of normal weight, overweight, and obese subjects, respectively. Biomarkers of liver fibrosis were comparable across subgroups, and LS was higher in obese, than in normal weight subjects. DOB was 23.2 ± 1.5‰ in normal weight subjects, tended to decrease in overweight (19.9 ± 1.0‰) and decreased significantly in obese subjects (16.9 ± 1.3, P = 0.008 vs. normal weight). Subjects with NAFLD had lower DOB (18.7 ± 0.9 vs. 22.1 ± 1.2, P = 0.03) but higher LS (4.7 ± 0.1 vs. 4.0 ± 0.2 kPa, P = 0.0003) than subjects without NAFLD, irrespective of fibrosis. DOB (but not cPDR) decreased with increasing degree of NAFLD (R = -0.26; P = 0.01) and LS (R = -0.23, P = 0.03). Patients with T2D showed increased rate of NAFLD than those without T2D but similar LS, DOB and cPDR.
Overweight, obesity and liver fat accumulation manifest with deranged portal extraction efficiency of methacetin into the steatotic hepatocyte. This functional alteration occurs early, and irrespective of significant fibrosis and presence of T2D.
在非酒精性脂肪性肝病（NAFLD）中，关于特定代谢途径导致早期肝功能障碍的事件仍知之甚少。
我们招募了84名肥胖和/或2型糖尿病（T2D）患者。采用FibroScan®通过受控衰减参数（CAP）评估NAFLD，通过肝脏硬度（LS）评估肝纤维化。排除LS高于7 kPa的患者。使用APRI和FIB-4作为肝纤维化的额外血清生物标志物。采用稳定同位素动态呼气试验评估口服（C）-美沙西汀的门静脉提取肝效率（以DOB表示）和微粒体代谢（以cPDR表示）。
正常体重、超重和肥胖受试者中NAFLD的发生率分别为45%、65.9%和91.3%。各亚组的肝纤维化生物标志物相当，肥胖受试者的LS高于正常体重受试者。正常体重受试者的DOB为23.2±1.5‰，超重受试者的DOB有下降趋势（19.9±1.0‰），肥胖受试者的DOB显著下降（16.9±1.3，与正常体重受试者相比，P = 0.008）。无论有无肝纤维化，患有NAFLD的受试者的DOB较低（18.7±0.9对22.1±1.2，P = 0.03），但LS较高（4.7±0.1对4.0±0.2 kPa，P = 0.0003）。DOB（而非cPDR）随NAFLD程度的增加而降低（R = -0.26；P = 0.01），也随LS的增加而降低（R = -0.23，P = 0.03）。与无T2D的患者相比，T2D患者的NAFLD发生率更高，但LS、DOB和cPDR相似。
超重、肥胖和肝脏脂肪堆积表现为美沙西汀进入脂肪变性肝细胞的门静脉提取效率紊乱。这种功能改变发生较早，且与显著肝纤维化和T2D的存在无关。
