超高场磁共振波谱在非酒精性脂肪性肝病中的应用：非酒精性脂肪性肝炎和肝纤维化能量代谢的新机制和诊断见解。
Ultra-high-field magnetic resonance spectroscopy in non-alcoholic fatty liver disease: Novel mechanistic and diagnostic insights of energy metabolism in non-alcoholic steatohepatitis and advanced fibrosis.
机构信息
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
High-Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
出版信息
Liver Int. 2017 Oct;37(10):1544-1553. doi: 10.1111/liv.13451. Epub 2017 May 20.
BACKGROUND & AIMS: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) non-invasive tools obtaining pathomechanistic insights to improve risk stratification are urgently needed. We therefore explored high- and ultra-high-field magnetic resonance spectroscopy (MRS) to obtain novel mechanistic and diagnostic insights into alterations of hepatic lipid, cell membrane and energy metabolism across the spectrum of NAFLD.
METHODS
MRS and liver biopsy were performed in 30 NAFLD patients with NAFL (n=8) or NASH (n=22). Hepatic lipid content and composition were measured using 3-Tesla proton ( H)-MRS. 7-Tesla phosphorus ( P)-MRS was applied to determine phosphomonoester (PME) including phosphoethanolamine (PE), phosphodiester (PDE) including glycerophosphocholine (GPC), phosphocreatine (PCr), nicotinamide adenine dinucleotide phosphate (NADPH), inorganic phosphate (Pi), γ-ATP and total phosphorus (TP). Saturation transfer technique was used to quantify hepatic ATP flux.
RESULTS
Hepatic steatosis in H-MRS highly correlated with histology (P<.001) showing higher values in NASH than NAFL (P<.001) without differences in saturated or unsaturated fatty acid indices. PE/TP ratio increased with advanced fibrosis (F3/4) (P=.002) whereas GPC/PME+PDE decreased (P=.05) compared to no/mild fibrosis (F0-2). γ-ATP/TP was lower in advanced fibrosis (P=.049), while PCr/TP increased (P=.01). NADPH/TP increased with higher grades of ballooning (P=.02). Pi-to-ATP exchange rate constant (P=.003) and ATP flux (P=.001) were lower in NASH than NAFL.
CONCLUSIONS
Ultra-high-field MRS, especially saturation transfer technique uncovers changes in energy metabolism including dynamic ATP flux in inflammation and fibrosis in NASH. Non-invasive profiling by MRS appears feasible and may assist further mechanistic and therapeutic studies in NAFLD/NASH.
背景与目的
随着非酒精性脂肪性肝病（NAFLD）和脂肪性肝炎（NASH）发病率的上升，迫切需要获得非侵入性工具来深入了解发病机制，以改善风险分层。因此，我们探索了高场和超高场磁共振波谱（MRS），以获得有关NAFLD 谱中肝脂质、细胞膜和能量代谢改变的新的发病机制和诊断见解。
方法
对 30 名 NAFLD 患者（NAFL 患者 8 名，NASH 患者 22 名）进行 MRS 和肝活检。使用 3T 质子（H）-MRS 测量肝脂质含量和组成。应用 7T 磷（P）-MRS 测定磷酸单酯（PME），包括磷酸乙醇胺（PE）、磷酸二酯（PDE），包括甘油磷酸胆碱（GPC）、磷酸肌酸（PCr）、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）、无机磷（Pi）、γ-ATP 和总磷（TP）。使用饱和转移技术定量肝 ATP 通量。
结果
H-MRS 中的肝脂肪变性与组织学高度相关（P<0.001），NASH 患者的数值高于 NAFL 患者（P<0.001），但饱和或不饱和脂肪酸指数无差异。PE/TP 比值随纤维化程度（F3/4）增加（P=0.002），而 GPC/PME+PDE 比值降低（P=0.05）与无/轻度纤维化（F0-2）相比。高级纤维化（P=0.049）时γ-ATP/TP 降低，而 PCr/TP 升高（P=0.01）。NADPH/TP 随气球样变程度增加而增加（P=0.02）。Pi 至 ATP 交换速率常数（P=0.003）和 ATP 通量（P=0.001）在 NASH 中均低于 NAFL。
结论
超高场 MRS，尤其是饱和转移技术，揭示了 NASH 中炎症和纤维化过程中能量代谢的变化，包括动态 ATP 通量。MRS 的无创谱分析似乎是可行的，可能有助于进一步研究 NAFLD/NASH 的发病机制和治疗方法。
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