非酒精性脂肪性肝病伴肥胖患者血清25羟维生素D的表达及其临床意义

Expression of serum 25-hydroxyvitamin D and its clinical significance in patients with nonalcoholic fatty liver disease and obesity

目的检测非酒精性脂肪性肝病(NAFLD)伴肥胖患者血清25羟维生素D的表达水平,分析25羟维生素D与机体肝功能、血脂及炎症指标的关系。方法选取2022年1月—2023年3月于山西白求恩医院就诊的NAFLD患者90例,根据BMI分为NAFLD伴肥胖组60例(BMI≥28 kg/m^(2))和NAFLD组30例(BMI<28 kg/m^(2));另选取同期健康体检者30例作为对照组。检测3组人群血清25羟维生素D、肝功能指标(ALT、AST、ALP、GGT、TBil、DBil)、血脂指标(HDL、LDL、TC、TG)、炎症指标(H-CRP、GP-73)以及细胞因子水平(IL-2、IL-4、IL-6、IL-10、IL-17、IL-1β、TNF-α、IFN-γ),测量肝脾体积比值。正态分布的计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验或Tamhane’s T2法;非正态分布的计量资料多组间比较及进一步两两比较均采用Kruskal-Wallis H检验。相关性采用Pearson或Spearman相关性分析。结果与对照组相比,NAFLD伴肥胖组25羟维生素D,HDL,细胞因子IL-2、IL-4、IL-10、IFN-γ和肝脾体积比值均显著降低(P值均<0.05),而肝功能指标ALT、AST、ALP、GGT、TBil、DBil,血脂指标LDL、TC、TG,炎症指标H-CRP、GP-73及细胞因子IL-1β、IL-17、TNF-α均明显升高(P值均<0.05)。NAFLD伴肥胖组与NAFLD组比较,除肝脾体积比值和H-CRP水平外,上述指标差异均有统计学意义(P值均<0.05)。相关性分析结果显示,25羟维生素D水平与ALT(r=-0.324,P=0.012)、AST(r=-0.421,P=0.001)、ALP(r=-0.435,P=0.001)、GGT(r=-0.343,P=0.007)、TBil(r=-0.532,P<0.001)、DBil(r=-0.521,P<0.001)、LDL(r=-0.405,P=0.001)、TC(r=-0.466,P<0.001)、TG(r=-0.551,P<0.001)、H-CRP(r=-0.434,P=0.014)、GP-73(r=-0.421,P=0.001)、IL-1β(r=-0.433,P=0.001)、IL-17(r=-0.465,P<0.001)和TNF-α(r=-0.533,P<0.001)呈负相关;与HDL(r=0.632,P<0.001)、IL-2(r=0.546,P<0.001)、IL-4(r=0.533,P<0.001)、IL-10(r=0.456,P<0.001)及肝脾体积比值(r=0.543,P<0.001)呈正相关。结论NAFLD伴肥胖患者血清25羟维生素D与肝功能、血脂及炎症指标均存在显著相关性,25羟维生素D可能通过减轻炎症反应缓解NAFLD伴肥胖患者症状,为NAFLD治疗提供新的干预策略。

Objective To investigate the serum level of 25-hydroxyvitamin D in patients with nonalcoholic fatty liver disease(NAFLD)and obesity,as well as the correlation of 25-hydroxyvitamin D with liver function,blood lipids,and inflammatory indicators.Methods A total of 90 patients with NAFLD who attended Shanxi Bethune Hospital from January 2022 to March 2023 were enrolled,and according to the body mass index(BMI),they were divided into NAFLD+obesity group with 60 patients(BMI≥28 kg/m^(2))and NAFLD group with 30 patients(BMI<28 kg/m^(2));30 individuals who underwent physical examination during the same period of time were enrolled as control group.Related indications were measured for all three groups,including serum 25-hydroxyvitamin D,liver function parameters(alanine aminotransferase[ALT],aspartate aminotransferase[AST],alkaline phosphatase[ALP],gamma-glutamyl transpeptidase[GGT],total bilirubin[TBil],and direct bilirubin[DBil]),blood lipid parameters(high-density lipoprotein[HDL],low-density lipoprotein[LDL],total cholesterol[TC],and triglyceride[TG]),inflammatory indicators(high-sensitivity C-reactive protein[H-CRP]and Golgi protein 73[GP-73]),cytokines(interleukin-2[IL-2],interleukin-4[IL-4],interleukin-6[IL-6],interleukin-10[IL-10],interleukin-17[IL-17],interleukin-1β[IL-1β],tumor necrosis factor-α[TNF-α],and interferon gamma[IFN-γ]),and liver/spleen volume ratio.A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the least significant difference t-test or the Tamhane’s T2 test was used for further comparison between two groups;the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups.A Pearson or Spearman correlation analysis was performed.Results Compared with the control group,the NAFLD+obesity group had significant reductions in 25-hydroxyvitamin D,HDL,cytokines(IL-2,IL-4,IL-10,and IFN-γ),and liver/spleen volume ratio(all P<0.05),as well as significant increases in liver function parameters(ALT,AST,ALP,GGT,TBil,and DBil),blood lipid parameters(LDL,TC,and TG),inflammatory indicators(H-CRP and GP-73),and cytokines(IL-1β,IL-17,and TNF-α)(all P<0.05).There were significant differences between the NAFLD+obesity group and the NAFLD group in all the above indicators except liver/spleen volume ratio and H-CRP(all P<0.05).The correlation analysis showed that 25-hydroxyvitamin D level was negatively correlated with ALT(r=-0.324,P=0.012),AST(r=-0.421,P=0.001),ALP(r=-0.435,P=0.001),GGT(r=-0.343,P=0.007),TBil(r=-0.532,P<0.001),DBil(r=-0.521,P<0.001),LDL(r=-0.405,P=0.001),TC(r=-0.466,P<0.001),TG(r=-0.551,P<0.001),H-CRP(r=-0.434,P=0.014),GP-73(r=-0.421,P=0.001),IL-1β(r=-0.433,P=0.001),IL-17(r=-0.465,P<0.001),and TNF-α(r=-0.533,P<0.001),and it was positively correlated with HDL(r=0.632,P<0.001),IL-2(r=0.546,P<0.001),IL-4(r=0.533,P<0.001),IL-10(r=0.456,P<0.001),and liver/spleen volume ratio(r=0.543,P<0.001).Conclusion Serum 25-hydroxyvitamin D is significantly correlated with liver function parameters,blood lipid parameters,and inflammatory indicators in patients with NAFLD and obesity,and it may alleviate the symptoms of patients with NAFLD and obesity by reducing inflammatory response,which provides new intervention strategies for the treatment of NAFLD.