维生素D缺乏对非酒精性脂肪性肝炎患者FIB-4指数及病情严重程度的影响

Influence of vitamin D deficiency on fibrosis-4 index and disease severity in patients with nonalcoholic steatohepatitis

目的探讨维生素D缺乏对非酒精性脂肪性肝炎(NASH)的影响。方法选取2020年1月—2021年10月冬春季在长沙市第一医院感染科住院治疗的NASH患者,根据血清1,25(OH)_(2)D_(3)水平分为3组:A组为1,25(OH)_(2)D_(3)缺乏组(<20 ng/mL),B组为1,25(OH)_(2)D_(3)不足组(20~30 ng/mL),C组为1,25(OH)_(2)D_(3)充足组(>30 ng/mL)。比较3组患者血清1,25(OH)_(2)D_(3)、ALT、AST、TBil、TC、TG、IL-18、IL-37水平和肝脏病理分级的差异,计算FIB-4指数。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。计数资料组间比较采用χ^(2)检验。相关性采用Pearson相关分析。结果共纳入NASH患者120例,A、B、C 3组各40例。与A组比较,B、C两组患者1,25(OH)_(2)D_(3)、IL-37水平升高,而FIB-4指数和ALT、AST、TBil、TC、TG、IL-18水平降低,差异均有统计学意义(P值均<0.05)。与B组比较,C组患者1,25(OH)_(2)D_(3)、IL-37水平升高,FIB-4指数和ALT、AST、TC、TG、IL-18水平降低,差异均有统计学意义(P值均<0.05)。相关性分析结果显示,1,25(OH)_(2)D_(3)与ALT(r=-0.84,P<0.001)、AST(r=-0.77,P<0.001)、TBil(r=-0.32,P<0.001)、TC(r=-0.45,P<0.001)、TG(r=-0.42,P<0.001)、IL-18(r=-0.40,P<0.001)及FIB-4指数(r=-0.62,P<0.001)均呈负相关,而与IL-37(r=0.59,P<0.001)呈正相关。与A组相比,B、C组中与重度脂肪变(χ^(2)=51.46,P<0.001)、桥接纤维化与早期肝硬化(χ^(2)=36.59,P<0.001)、桥接坏死与大片坏死(χ^(2)=37.28,P<0.001)比例下降。光镜示A组肝细胞广泛气球样变,大量大泡性为主的脂滴,肝板排列紊乱,淋巴细胞浸润,局灶桥接纤维化;B组多数为点灶坏死,门静脉周围纤维化,脂滴大小不等,少量中性粒细胞浸润,部分肝细胞气球样变;C组少量肝细胞气球样变,局灶窦周纤维化,少数点灶坏死,肝细胞胞质可见少量脂滴。结论维生素D水平越低,NASH患者肝损伤、肝纤维化程度越明显,检测维生素D有助于评估NASH患者病情进展情况。

Objective To investigate the influence of vitamin D deficiency on nonalcoholic steatohepatitis(NASH).Methods The pa-tients with NASH who were hospitalized in Department of Infectious Diseases,The First Hospital of Changsha,from January 2020 to October 2021 were enrolled,and according to the serum level of 1,25(OH)_(2)D_(3),they were divided into group A with 1,25(OH)_(2)D_(3) deficiency(<20 ng/mL),group B with 1,25(OH)_(2)D_(3) insufficiency(20-30 ng/mL),and group C with sufficient 1,25(OH)_(2)D_(3)(>30 ng/mL).The three groups were compared in terms of the serum levels of 1,25(OH)_(2)D_(3),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),total cholesterol(TC),triglyceride(TG),interleukin-18(IL-18),and interleukin-37(IL-37)and liver pathological grade,and fibrosis-4(FIB-4)index was calculated.A one-way analysis of variance was used for comparison of con-tinuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the chi-square test was used for comparison of categorical data between groups.A Pearson correlation analysis was also performed.Results A total of 120 NASH patients were enrolled,with 40 patients in each group.Compared with group A,groups B and C had significant increa-ses in the levels of 1,25(OH)_(2)D_(3) and IL-37 and significant reductions in FIB-4 index and the levels of ALT,AST,TBil,TC,TG,and IL-18(all P<0.05).Compared with group B,group C had significant increases in the levels of 1,25(OH)_(2)D_(3) and IL-37 and signifi-cant reductions in FIB-4 index and the levels of ALT,AST,TC,TG,and IL-18(all P<0.05).The correlation analysis showed that 1,25(OH)_(2)D_(3) was negatively correlated with ALT(r=-0.84,P<0.001),AST(r=-0.77,P<0.001),TBil(r=-0.32,P<0.001),TC(r=-0.45,P<0.001),TG(r=-0.42,P<0.001),IL-18(r=-0.40,P<0.001),and FIB-4 index(r=-0.62,P<0.001),and it was positively correlated with IL-37(r=0.59,P<0.001).Compared with group A,groups B and C had significant re-ductions in the proportion of patients with severe steatosis(χ^(2)=51.46,P<0.001),bridging fibrosis and early liver cirrhosis(χ^(2)=36.59,P<0.001),or bridging necrosis and large-scale necrosis(χ^(2)=37.28,P<0.001).Light microscopy showed that group A had extensive ballooning degeneration of hepatocytes,a large number of lipid droplets(mainly macrovesicular lipid droplets),disordered arrangement of the liver plate,lymphocyte infiltration,and focal bridging fibrosis;group B mainly had spotted focal necrosis,periportal fibrosis,lipid drop-lets with various sizes,a small amount of neutrophil infiltration,and ballooning degeneration of some hepatocytes;group C had ballooning degeneration of a small number of hepatocytes,focal perisinusoidal fibrosis,a small number of lesions with spotted focal necrosis,and a small number of lipid droplets in the cytoplasm of hepatocytes.Conclusion The degree of liver injury and fibrosis increases with the reduc-tion in vitamin D level,and vitamin D measurement helps to evaluate the progression of NASH.