性激素结合球蛋白与非酒精性脂肪性肝炎的相关性研究

Association between serum sex hormone-binding globulin and non-alcoholic steatohepatitis

目的研究血清性激素结合球蛋白(SHBG)与非酒精性脂肪性肝炎(NASH)之间的相关性。方法横断面研究。纳入2016年1月至2021年4月于南京大学医学院附属鼓楼医院住院且行肝脏穿刺检查的中青年肥胖患者371例,根据肝脏病理结果及评分分为非酒精性脂肪性肝病(NAFLD)组(328例)和对照组(非-NAFLD,43例),前者进一步分为非酒精性肝脂肪变(NAFL)亚组(60例)、NASH可能亚组(172例)和NASH亚组(96例)。比较各组间血清SHBG水平;根据NAFLD患者血清SHBG水平的三分位数进行划分,比较不同SHBG水平亚组NAFLD患者肝脏病理特征。通过logistic回归分析NASH发生的危险因素并建立预测模型,并采用受试者工作特征(ROC)曲线评估该模型对NASH的诊断价值。结果371例患者年龄(32±10)岁,体重指数(39.16±6.58)kg/m2,其中女性236例(63.6%)。NAFLD组患者血清SHBG水平[M(Q1,Q3)]低于对照组[16.90(11.43,23.00)比23.45(15.40,31.22)mmol/L,P<0.05],且在NAFL、NASH可能以及NASH亚组中逐渐递减[(22.24±10.47)、(20.57±19.58)、(15.80±8.74)mmol,P<0.05]。低水平SHBG亚组的肝脏脂肪变评分和小叶炎症评分显著高于高水平SHBG亚组[(2.09±0.80)比(1.51±0.72)分,(1.10±0.68)比(0.85±0.68)分;P值均<0.05]。多因素logistic回归分析结果提示,低水平血清SHBG是NASH发生的独立危险因素(OR=2.527,95%CI:1.296~4.928,P<0.05)。SHBG联合天冬氨酸转氨酶辅助预测NAFLD患者发生NASH的ROC曲线下面积为0.752(95%CI:0.696~0.809)。结论低水平血清SHBG水平与NASH的发生相关。

Objective To investigate the association between serum sex hormone-binding globulin(SHBG)and non-alcoholic steatohepatitis(NASH).Methods In this cross-sectional study,a total of 371 middle-aged and young obese patients who were hospitalized and underwent liver puncture in Nanjing Drum Tower Hospital from January 2016 to April 2021 were included.The population was divided into control group(n=43)and non-alcoholic fatty liver disease(NAFLD)group(n=328)based on the non-alcoholic fatty liver disease activity score.Subjects in NAFLD group were further divided into non-alcoholic fatty liver(NAFL)(n=60),uncertain-NASH(n=172),and NASH(n=96).Serum SHBG was tested in patients with NAFLD who were divided into three subgroups according to tertiles.The liver pathological characteristics in different SHBG level subgroups were compared.The risk factors of NASH were analyzed by logistic regression.The prediction model of NASH noninvasive diagnosis was established by forward stepwise regression,and the diagnostic value of non-invasive model for NASH was evaluated by receiver operating characteristic(ROC)curve.Results The median age in patients were(32±10)years old with a body mass index of(39.16±6.58)kg/m²,including 236 females(63.6%).Serum SHBG level[M(Q1,Q3)]in NAFLD group was significantly lower than that in control group[16.90(11.43,23.00)vs.(23.45(15.40,31.22)mmol/L,P<0.05],and progressively diminished in NAFL,uncertain-NASH and NASH subgroups[(22.24±10.47),(20.57±19.58),(15.80±8.74)mmol;P for trend<0.05].Compared with the high-leveled SHBG subgroup,the steatosis score(2.09±0.80 vs.1.51±0.72,P<0.01)and lobular inflammation score(1.10±0.68 vs.0.85±0.68,P<0.05)were significantly higher in the low-leveled SHBG group.Multivariate logistic regression analysis indicated that lower serum SHBG level was an independent risk factor for NASH(OR=2.527,95%CI:1.296 to 4.928,P<0.05).The area under ROC curve of SHBG combined with aspartate aminotransferase in predicting NASH in NAFLD patients was 0.752(95%CI:0.696 to 0.809).Conclusion Low serum SHBG level is associated with NASH.