The Role of Liver Fat and Insulin Resistance as Determinants of Plasma Aminotransferase Elevation in Nonalcoholic Fatty Liver Disease
The Role of Liver Fat and Insulin Resistance as Determinants of Plasma Aminotransferase Elevation in Nonalcoholic Fatty Liver Disease
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DOI：
10.1002/hep.27395
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发表时间：
2015-01-01
期刊：
影响因子：
13.5
通讯作者：
Cusi, Kenneth
中科院分区：
文献类型：
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作者：
Maximos, Maryann;Bril, Fernando;Cusi, Kenneth
非酒精性脂肪肝 (NAFLD) 患者的血浆转氨酶（天冬氨酸转氨酶 [AST] 和丙氨酸转氨酶 [ALT]）通常升高。然而，其升高背后的因素仍不清楚。本研究的目的是评估 ALT 水平正常或升高的 NAFLD/非酒精性脂肪性肝炎 (NASH) 患者中胰岛素抵抗 (IR) 和肝脏甘油三酯含量与组织学的关系。为此，我们招募了 440 名患者，分为三组：无 NAFLD（n=60）； ALT 正常的 NAFLD (n=165)；以及伴有 ALT 升高的 NAFLD (n=215)。我们测量：（1）通过质子磁共振波谱（H-1-MRS）检测肝脏脂肪； (2) 活检显示的肝病严重程度（n=293）； (3)通过使用3-H-3-葡萄糖的正常血糖高胰岛素钳夹测量肝脏、肌肉和脂肪组织中的胰岛素敏感性。患有 NAFLD 且 ALT 升高的患者，即使体重指数与 ALT 正常的患者非常匹配，其脂肪组织胰岛素抵抗也较差（ATIR；P
Plasma aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) are usually increased in patients with nonalcoholic fatty liver disease (NAFLD). However, the factors behind their elevation remain unclear. The aim of this study was to assess the role of insulin resistance (IR) and liver triglyceride content in relation to histology in patients with NAFLD/nonalcoholic steatohepatitis (NASH) with normal or elevated ALT levels. To this end, we enrolled 440 patients, divided into three groups: no NAFLD (n=60); NAFLD with normal ALT (n=165); and NAFLD with elevated ALT (n=215). We measured: (1) liver fat by proton magnetic resonance spectroscopy (H-1-MRS); (2) severity of liver disease by biopsy (n=293); and (3) insulin sensitivity in liver, muscle, and adipose tissue by a euglycemic hyperinsulinemic clamp with 3-H-3-glucose. Patients with NAFLD and elevated ALT, even when well matched for body mass index to those with normal ALT, had worse adipose tissue insulin resistance (ATIR; P