儿童IgG4相关自身免疫性肝炎临床与病理特征分析*

目的 探讨儿童免疫球蛋白G4相关自身免疫性肝炎(IgG4-AIH)患者临床和肝组织病理学特征。方法 2014年6月～2019年6月我科收治的AIH儿童38例,符合2008年国际AIH小组(IAIHG)制定的简化诊断积分系统或1999年IAIHG制定的AIH诊断评分系统。根据肝组织IgG4阳性浆细胞浸润≥10个/高倍镜视野(HPF)诊断IgG4-AIH。采用ELISA法检测血清IgG和IgG4。常规行肝穿刺,采用免疫组织化学染色检测肝组织IgG4阳性浆细胞。结果 在38例AIH患者中,诊断IgG4-AIH患者4例,AIH患者34例;IgG4-AIH患者血清IgG和IgG4水平分别为22.6(13.2, 29.8)mg/dL和226.5(105.8,424.6)mg/dL,与AIH患者的18.9(10.4,25.3)mg/dL和209.4(96.1,401.6)mg/dL比,差异无统计学意义(P>0.05);IgG4-AIH组肝组织IgG4阳性浆细胞计数/HPF为40.2(25.4,55.7),显著高于AIH组患者;IgG4-AIH组肝组织IgG4阳性浆细胞计数与炎性反应活动分级(r=0.48)和肝纤维化分期(r=0.37)呈正相关(P<0.05);IgG4-AIH患者血清ALT恢复正常所需要的时间为(3.5±0.8)w,显著短于AIH组,血清AST恢复时间为(3.6±0.6)w,显著短于AIH组,血清碱性磷酸酶恢复时间为(4.0±1.1)w,显著短于AIH组,血清谷氨酰转肽酶恢复时间为(4.2±1.5)w,显著短于AIH组,血清IgG水平恢复正常的时间为(7.6±2.8)w,显著短于AIH组。结论 IgG4-AIH儿童具有AIH的基本特征,血清IgG4水平并不比AIH患者更高,但肝组织IgG4阳性浆细胞浸润显著多于AIH患者。另外,IgG4-AIH儿童对皮质激素治疗具有良好的应答反应,血清学指标的恢复时间也相对较短,这些特征有助于临床诊断。本组IgG4-AIH儿童例数太少,其结论有待于验证。

Clinical and pathological features of IgG4-related autoimmune hepatitis in children

Objective The aim of this study was to investigate the clinical and pathological characteristics of immunoglobulin G4-associated autoimmune hepatitis(IgG4-AIH)in children.Methods 38 children with AIH were enrolled in our hospital between June 2014 and June 2019,and the diagnostic criteria was based on the simplified diagnostic scoring system reported by the International Autoimmune Hepatitis Group(IAIHG)in 2008 or the AIH diagnostic scoring system established by IAIHG in 1999.According to Umemura et al and other scholars’s reports,IgG4-AIH was diagnosed by hepatic IgG4 positive plasma cell infiltration≥10/high power field of vision(HPF)and serum IgG4≥135 mg/dl.Serum IgG and IgG4 levels were detected by ELISA,and liver biopsies were performed routinely.The hepatic IgG4 positive plasma cell infiltration was evaluated by immunohistochemical staining.Results Out of the 38 patients with AIH included,four were diagnosed as IgG4-AIH and thirty-four were classical AIH;serum IgG and IgG4 levels in patients with IgG4-AIH were 22.6(13.2,29.8)mg/dL and 226.5(105.8,424.6)mg/dL,not significantly different as compared to 18.9(10.4,25.3)mg/dL and 209.4(96.1,401.6)mg/dL in patients with AIH(P>0.05);the hepatic IgG4 positive plasma cell infiltration in patients with IgG4-AIH were 40.2(25.4,55.7)/HPF,significantly higher than[17.6(9.2,30.7)/HPF,P<0.05]in patients with AIH;the hepatic IgG4 positive plasma cell infiltration in patients with IgG4-AIH were positively correlated to histological activity index(r=0.48)and liver fibrosis staging(r=0.37,P<0.05);the returning to normal time for serum ALT in patients with IgG4-AIH was(3.5±0.8)w,significantly shorter than[(6.8±2.7)w,P<0.05]in patients with AIH,the returning to normal time for serum AST level was(3.6±0.6)w,much shorter than[(6.5±1.4)w,P<0.05],for ALP was(4.0±1.1)w,much shorter than[(6.4±1.5)w,P<0.05],for GGT was(4.2±1.5)w,significantly shorter than[(7.0±2.2)w,P<0.05],and for serum IgG back to normal was(7.6±2.8)w,also much shorter than[(13.8±6.3)w,P<0.05]in patients with AIH.Conclusions Children with IgG4-AIH have the same as serum IgG4 levels in kits with AIH,while the infiltration of IgG4 positive plasma cells in liver tissues is significantly higher than that in children with AIH.In addition,the children with IgG4-AIH have a good therapeutic response to hormone therapy,and the recovery times of serological indexes are much quick.Our findings should be validated by multi-central studies because of too little cases with IgG4-AIH in our study.