血清铁蛋白水平与初治自身免疫性肝炎晚期肝纤维化的关系

摘要/Abstract

摘要： 目的探讨血清铁蛋白水平与初治自身免疫性肝炎(AIH)肝纤维化状态的关系。方法纳入2012年1月至2022年6月吉林大学第一医院92例AIH患者,根据肝活检结果,分为非晚期纤维化组(n=57)和晚期纤维化组(n=35)。肝纤维化分期评估基于Batts-Ludwig评分系统,其中定义F3、F4期为晚期肝纤维化,F0～F2期为非晚期肝纤维化,比较两组临床资料,分析影响AIH晚期肝纤维化的因素。结果非晚期纤维化组年龄、IgG、TBil、PT、铁蛋白以及TSI分别为(51.0±11.8)岁、14.9(12.8,18.9)g/L、17.1(11.6,32.7)μmol/L、(12.2±1.0)s、124.3(44.6,305.4)μg/L及33.2(23.0,57.8)%,均低于晚期肝纤维化组的(58.1±9.3)岁、18.5(15.8,24.2)g/L、28.2(15.7,92.7)μmol/L、(13.9±1.2)s、352.7(183.0,740.6)μg/L及55.0(41.2,69.8)%(P<0.05);而非晚期纤维化组Alb、PLT、转铁蛋白、UIBC以及TIBC分别为(41.0±4.8)g/L、(210.4±36.5)×10⁹/L、2.7(2.3,3.2)g/L、39.0(23.4,51.2)μmol/L及64.0(56.5,71.0)μmol/L,分别显著高于晚期肝纤维化组的(38.1±5.1)g/L、(122.3±23.5)×10⁹/L、2.4(2.1,2.8)g/L、25.1(16.3,31.4)μmol/L及55.6(50.7,60.8)μmol/L(P<0.05)。相关性分析可知血清铁与铁蛋白、TSI呈正相关(r=0.44、0.93),与转铁蛋白、UIBC和TIBC呈负相关(r=-0.44、-0.82、-0.25);血清铁、铁蛋白和TSI与年龄、TBil和肝纤维化分期呈正相关(r=0.30、0.49、0.24;0.34、0.39、0.40;0.37、0.52、0.29),而转铁蛋白、UIBC和TIBC与年龄、TBil和纤维化分期呈负相关(r=-0.41、-0.22、-0.24;-0.38、-0.52、-0.94;-0.36、-0.25、-0.48);血清铁、铁蛋白和TSI与ALT、AST呈正相关(r=0.34、0.45;0.42、0.47;0.33、0.45),而UIBC与ALT、AST呈负相关(r=-0.31、-0.40);血清铁和TSI与Alb、PLT呈负相关(r=-0.39、-0.20),而转铁蛋白、UIBC和TIBC与Alb、PLT呈正相关(r=0.35、0.34;0.53、0.33;0.40、0.39);TSI与PT呈正相关(r=0.23,P<0.05),TIBC与PT呈负相关(r=-0.22,P<0.05)。多因素分析提示IgG(OR=1.10,95%CI:1.03～1.21)、PLT(OR=0.98,95%CI:0.97～0.99)、PT(OR=1.73,95%CI:1.16～2.68)和铁蛋白(OR=1.02,95%CI:1.01～1.04)是预测AIH患者晚期肝纤维化的独立影响因素。结论在初治AIH患者中血清铁蛋白升高与晚期肝纤维化独立相关。

关键词: 自身免疫性肝炎, 血清铁蛋白, 肝纤维化

Abstract: Objective To investigate the relationship between serum ferritin level and liver fibrosis in patients newly diagnosed with autoimmune hepatitis (AIH).Methods A total of 92 patients with AIH who had undergone liver biopsy before receiving immunosuppressive therapy from January 2012 to June 2022 were reviewed. The patients consisted of 15 males and 77 females, with a mean age of 54.0±11.3 years. The assessment of hepatic fibrosis stages was based on Batts-Ludwig scoring system, in which F3 and F4 stages were defined as advanced hepatic fibrosis, and F0-F2 stages were non-advanced hepatic fibrosis. The clinical data of the two groups and the correlation among the data were compared, and the factors that affect the advanced hepatic fibrosis of AIH were analyzed.Results Based on the results of liver biopsy, the patients were divided into non-advanced fibrosis group (n=57) and advanced fibrosis group (n=35). In AIH patients, the age, IgG, TBil, PT, ferritin and TSI of non-advanced fibrosis group were (51.0±11.8) years old, 14.9(12.8, 18.9)g/L, 17.1(11.6, 32.7)μmol/L, (12.2±1.0)s, 124.3(44.6, 305.4)μg/L and 33.2(23.0, 57.8)%, respectively, which were significantly lower than those in advanced hepatic fibrosis group [(58.1±9.3) years, 18.5(15.8, 24.2)g/L, 28.2(15.7, 92.7)μmol/L, (13.9±1.2)s, 352.7(183.0, 740.6)μg/L and 55.0(41.2, 69.8)%, P<0.05]. While in the non-advanced fibrosis group, Alb, PLT, transferrin, UIBC and TIBC [(41.0±4.8) g/L, (210.4±36.5) × 10⁹/L, 2.7(2.3, 3.2)g/L, 39.0(23.4, 51.2) and 64.0(56.5, 71.0)]μmol/L were significantly higher than those of advanced hepatic fibrosis group [(38.1±5.1) g/L, (122.3±23.5) × 10⁹/L, 2.4(2.1, 2.8)g/L, 25.1(16.3, 31.4)μmol/L and 55.6 (50.6, 60.8)μmol/L, P<0.05]. Correlation analysis showed that serum iron was positively correlated with ferritin and TSI (r=0.44, 0.93) (P<0.05), and negatively correlated with transferrin, UIBC and TIBC (r=-0.44, -0.82, -0.25) (P<0.05). Serum iron, ferritin and TSI were positively correlated with age, TBil and hepatic fibrosis stage (r=0.30, 0.49, 0.24; 0.34, 0.39, 0.40; 0.37, 0.52, 0.29) (P<0.05), while transferrin, UIBC and TIBC were negatively correlated with age, TBil and fibrosis stage (r=-0.41, -0.22, -0.24; -0.38, -0.52, -0.94; -0.36, -0.25, -0.48, P<0.05). Serum iron, ferritin and TSI were positively correlated with ALT and AST (r=0.34, 0.45; 0.42, 0.47; 0.33, 0.45) (P<0.05), while UIBC was negatively correlated with ALT and AST (r=-0.31, -0.40) (P<0.05); serum iron and TSI were negatively correlated with Alb and PLT (r=-0.39, -0.20) (P<0.05), while transferrin, UIBC and TIBC were positively correlated with Alb and PLT (r=0.35, 0.34; 0.53, 0.33; 0.40, 0.39) (P<0.05); there was a positive correlation between TSI and PT (r=0.23) (P<0.05), and a negative correlation between TIBC and PT (r=-0.22) (P<0.05). Multivariate analysis showed that IgG, PLT, PT and ferritin were independent factors to predict advanced liver fibrosis in patients with AIH, and the odds ratios (OR)(95%CI) were 1.10 (1.03~1.21), 0.98 (0.97~0.99), 1.73 (1.16~2.68) and 1.02 (1.01~1.04), respectively.Conclusion The increased serum ferritin level in newly diagnosed AIH patients is independently related to advanced hepatic fibrosis.

Key words: Autoimmune hepatitis, Serum ferritin, Liver fibrosis

裴宇梅, 张智慧, 连丽丽. 血清铁蛋白水平与初治自身免疫性肝炎晚期肝纤维化的关系[J]. 肝脏, 2023, 28(8): 961-964.

PEI Yu-mei, ZHANG Zhi-hui, LIAN Li-li. Relationship between serum ferritin level and advanced hepatic fibrosis in newly diagnosed autoimmune hepatitis[J]. Chinese Hepatolgy, 2023, 28(8): 961-964.

参考文献

[1] Kim WR, Berg T, Asselah T, et al. Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients. J Hepatol, 2016, 64(4):773-780.
[2] Yang YT, Wang LL, Yan LT, et al. Platelet count is closely associated with the severity of liver injury in patients with chronic hepatitis B virus infection: a cross-sectional study. Exp Ther Med, 2020, 20(1):243-250.
[3] Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol, 1999, 31(5):929-938.
[4] Hennes EM, Zeniya M, Czaja AJ, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology, 2008, 48(1):169-176.
[5] Sebastiani G, Tempesta D, Alberti A. Hepatic iron overload is common in chronic hepatitis B and is more severe in patients coinfected with hepatitis D virus. J Viral Hepat, 2012, 19(2):e170-e176.
[6] D'Souza RF, Feakins R, Mears L, et al. Relationship between serum ferritin, hepatic iron staining, diabetes mellitus and fibrosis progression in patients with chronic hepatitis C. Aliment Pharmacol Ther, 2005, 21(5):519-524.
[7] Bell H, Skinningsrud A, Raknerud N, et al. Serum ferritin and transferrin saturation in patients with chronic alcoholic and non-alcoholic liver diseases. J Intern Med, 1994, 236(3):315-322.
[8] Bugianesi E, Manzini P, D'Antico S, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology, 2004, 39(1):179-187.
[9] Ganz T. Systemic iron homeostasis. Physiol Rev, 2013, 93(4):1721-1741.
[10] Galicia-Moreno M, Gutiérrez-Reyes G. The role of oxidative stress in the development of alcoholic liver disease. Rev Gastroenterol Mex, 2014, 79(2):135-144.
[11] Taubert R, Hardtke-Wolenski M, Noyan F, et al. Hyperferritinemia and hypergammaglobulinemia predict the treatment response to standard therapy in autoimmune hepatitis. PLoS One, 2017, 12(6):e0179074.
[12] Martín-González C, Pelazas-González R, Fernández-Rodríguez C, et al. Ferritin and liver fibrosis among patients with chronic hepatitis C virus infection. J Trace Elem Med Biol, 2020, 61:126542.

[1]	孙成林, 孙亚朦, 陈姝延, 尤红. 非酒精性脂肪性肝病无创评估的应用与前景[J]. 肝脏, 2023, 28(8): 889-891.
[2]	陈勇良, 赵辉, 王晓静, 李秋雨, 潘丽, 李振燕. 肝静脉彩色多普勒血流频谱在肝纤维化分期中的临床价值[J]. 肝脏, 2023, 28(8): 907-911.
[3]	郑慕阳, 胡海, 范显文. 急性表现的自身免疫性肝炎的临床和病理特征分析[J]. 肝脏, 2023, 28(8): 953-956.
[4]	陈黎霞, 沈丽磊, 郑毅. 红细胞分布宽度-血小板比值评估自身免疫性肝炎患者肝纤维化严重程度的回顾性研究[J]. 肝脏, 2023, 28(8): 957-960.
[5]	魏伟, 王煜, 金杭斌, 郑亦农. 原发性胆汁性胆管炎并发或不并发自身免疫性疾病患者的临床特点及预后分析[J]. 肝脏, 2023, 28(8): 965-967.
[6]	张明明, 汪艳. 线粒体应激参与慢性乙型肝炎肝损伤的机制研究[J]. 肝脏, 2023, 28(7): 743-745.
[7]	施霞, 倪雪君, 马鑫, 武豆, 黄晨. 剪切波弹性成像在评估自身免疫性肝炎患者肝纤维化和治疗反应中的作用[J]. 肝脏, 2023, 28(7): 772-774.
[8]	赵心怡, 孙杰, 徐炜新. 血清Maresin-1水平变化对非酒精性脂肪性肝病的影响[J]. 肝脏, 2023, 28(7): 806-809.
[9]	王会迟, 田璐, 郑毅, 赵鹏, 董海苓, 边毓尧. 82例急性自身免疫性肝炎临床、生化和组织学特征[J]. 肝脏, 2023, 28(6): 716-719.
[10]	刘雅妮, 郭瑞芳, 王欢, 娄婷婷, 李燕. 氧化应激参与肝纤维化发生发展的研究进展[J]. 肝脏, 2023, 28(6): 724-727.
[11]	肖滢, 吴治念, 王亚东. 肝素非抗凝作用在肝病应用中的研究进展[J]. 肝脏, 2023, 28(6): 730-733.
[12]	严景全, 刘娟, 卢雪兰, 蓝云翠, , 林占洲. 直接抗病毒药物对持续病毒学应答慢性丙型肝炎患者肝纤维化的影响[J]. 肝脏, 2023, 28(5): 530-533.
[13]	冯薇薇, 孔严, 康茹. 慢性丙型肝炎合并代谢相关脂肪性肝病患者的临床特征及预后评价[J]. 肝脏, 2023, 28(5): 534-536.
[14]	张朋垒, 张明婷, 郝礼森, 靳丽敏, 潘恩亮, 何宇, 苗笑佳, 王薇. 四氯化碳诱导的大鼠肝纤维化肝组织中SHP2表达与在体肝星状细胞活化及增殖的关系[J]. 肝脏, 2023, 28(5): 549-553.
[15]	李庆鑫, 尹卿, 关瑛琦, 邵春红. 幽门螺杆菌感染与自身免疫性肝病关系的分析[J]. 肝脏, 2023, 28(5): 590-592.