The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease.
The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease.
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DOI：
10.1038/ctg.2016.72
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发表时间：
2017-01-26
影响因子：
3.6
通讯作者：
Miller KK
中科院分区：
文献类型：
--
作者：
Dichtel LE;Corey KE;Misdraji J;Bredella MA;Schorr M;Osganian SA;Young BJ;Sung JC;Miller KK
非酒精性脂肪性肝病（NAFLD）发展和进展为非酒精性脂肪性肝炎（NASH）的机制尚不完全清楚。越来越多的证据表明，生长激素（GH）和胰岛素样生长因子-1（IGF-1）可能在NAFLD的发生和进展中发挥作用。我们假设，在一组经过肝脏活检的精确表型肥胖受试者中，较低的血清IGF-1水平与肝脏脂肪积累、炎症和纤维化增加相关。在美国马萨诸塞州波士顿的马萨诸塞州总医院和美国弗吉尼亚州里士满的圣玛丽医院进行了一项回顾性横断面研究。在NAFLD检查或减肥手术期间对142名受试者进行肝活检，并由一名单盲病理学家进行分级。主要结果指标包括肝脏组织学和血清IGF-1。平均年龄为52 ± 10岁，体重指数（BMI）为43 ± 9 kg/m2。平均血清IGF-1在小叶炎症受试者中较低（112 ± 47 vs. 136 ± 57 ng/ml，P = 0.01），肝细胞气球样变（115 ± 48 vs. 135 ± 57 ng/ml，P = 0.05）、较高纤维化分期（2 - 4期vs. 0 - 1; 96 ± 40 vs. 125 ± 51 ng/ml，P = 0.005）和NASH（109 ± 45 vs. 136 ± 57 ng/ml，P = 0.002）。在控制了年龄、BMI和糖尿病诊断后，所有结果仍具有显著性，在排除肝硬化患者后，除肝细胞气球样变（趋势，P = 0.06）外，所有结果仍具有显著性。脂肪变性与平均血清IGF-1水平无显著相关性。当严格控制年龄、BMI、糖尿病的存在和排除肝硬化受试者后，低血清IGF-1水平与NAFLD组织学严重程度增加相关。进一步的研究是必要的，以确定GH和IGF-1对NAFLD的发展和进展的差异作用，这可以进一步阐明病理生理学和确定治疗靶点。
The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies. A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1. Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m2. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2–4 vs. 0–1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels. Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets.