幽门螺杆菌感染与自身免疫性肝病关系的分析

摘要/Abstract

摘要： 目的回顾性分析本院首诊、符合纳入标准的AILD患者临床资料,探讨Hp感染对上述AILD患者发生、发展的影响。方法 2015年9月—2022年2月期间于聊城市中医医院首诊AILD患者74例,其中男性43例、女性31例,年龄(58.2±12.5)岁。AIH、PBC及PSC符合标准。使用14C-UBT、胃窦组织快速尿速酶试验了解Hp感染情况,根据Hp感染与否状态对本院首诊AILD病例分组,比较不同分组肝功能、自身抗体、淋巴细胞亚群及肝组织病理改变程度。结果 74例AILD患者中AIH、PBC及PSC分别为34例(45.9%)、33例(44.6%)及7例(9.5%),依据14C-UBT结果分为Hp阳性、阴性组。前者ANA、AMA、SMA、ANCA、AMA-M2及LKM-1为20例(45.4%)、18例(40.9%)、17例(38.6%)、23例(52.2%)、25例(56.8%)及21例(47.7%),分别显著高于Hp阴性组[6例(20.0%)、4例(13.3%)、4例(13.3%)、5例(16.7%)、2例(6.7%)及2例(6.7%),P<0.05]。Hp阳性组CD3⁺CD4⁺ T细胞、CD4⁺/CD8⁺及CD3^-CD19⁺ B细胞为(42.1±6.2)%、(1.9±0.8)及(15.2±3.5)%,分别显著高于Hp阴性组[(37.7±5.5)%、(1.4±0.5)及(11.9±2.5)%,P<0.05];Hp阳性组CD3⁺CD8⁺ T细胞及CD3^-CD16⁺CD56⁺ NK细胞为(25.4±5.0)%及(11.7±2.8)%,分别显著低于[(29.0±5.1)%及(19.7±3.7)%,P<0.05]。Hp阳性组[30例(68.2%)]≥F3期高于Hp阴性组[13例(43.3%),P<0.05],同时前者[24例(54.6%)]≥G3级也高于后者[8例(26.7%),P<0.05]。结论超半数AILD患者存在Hp感染,与多种自身抗体增加和淋巴细胞亚群紊乱密切相关,可导致肝组织纤维化分期、炎症活动分级增加。

关键词: 自身免疫性肝病, 幽门螺杆菌, 自身抗体, 淋巴细胞亚群, 肝纤维化分期, 炎症活动分级

Abstract: Objective To review the clinical data of AILD patients who were first diagnosed in our hospital and met the inclusion criteria, and to explore the influence of Hp infection on the occurrence and development of AILD.Methods From 2015.9 to 2022.2, 74 patients with AILD first diagnosed were reviewed, including 43 males and 31 females, aged (58.2±12.5) years. The diagnosis of AIH, PBC and PSC met the standard. 14C-UBT and gastric antrum rapid urokinase test were used to understand the Hp infection. The first diagnosed AILD cases in Liaocheng Traditional Chinese Medicine Hospital were divided into groups according to the status of Hp infection or not, and the liver function, autoantibodies, lymphocyte subsets and pathological changes of liver tissues in different groups were compared.Results Among 74 patients with AILD, AIH, PBC and PSC were 34 cases (45.9%), 33 cases (44.6%) and 7 cases (9.5%), respectively. According to the results of 14C-UBT, they were divided into Hp positive group (44 cases, 59.5%) and Hp negative group (30 cases, 40.5%) in this study. In Hp positive group, ANA, AMA, SMA, ANCA, AMA-M2 and LKM-1 were 20 cases (45.4%), 18 cases (40.9%), 17 cases (38.6%), 23 cases (52.2%), 25 cases (56.8%) and 21 cases (47.9%), which were significantly higher than those in Hp negative group [6 cases (20.0%), 4 cases (13.3%), 4 cases (13.3%), 5 cases (16.7%), 2 cases (6.7%) and 2 cases (6.7%), P<0.05]. The percentages of CD3⁺CD4⁺T cells, CD4⁺/CD8⁺ and CD3^-CD19⁺B cells in Hp positive group were (42.1±6.2)%, (1.9±0.8) and (15.2±3.5)%, which were significantly higher than those in Hp negative group [(37.7±5.5)%, (1.4±0.5) and (11.9±2.5)%, respectively, P<0.05]. In Hp positive group, CD3⁺CD8⁺T cells and CD3^-CD16⁺CD56⁺NK cells were (25.4±5.0)% and (11.7±2.8)% in this study, which were significantly lower than [(29.0±5.1)% and (19.7±3.7)% respectively, P<0.05]. The proportion of Hp positive group [30 cases (68.2%)] ≥F3 was significantly higher than that of Hp negative group [13 cases (43.3%), P<0.05], at the same time, the former [24 cases (54.6%)] ≥ G3 grade was higher than the latter [8 cases (26.7%), P<0.05].Conclusion More than half of AILD patients are infected with Hp, which is closely related to the increase of various autoantibodies and the disorder of lymphocyte subsets, which can lead to the increase of liver fibrosis stage and inflammatory activity grade.

Key words: Autoimmune liver disease, Helicobacter pylori, Autoantibody, Lymphocyte subsets, Hepatic fibrosis staging, Inflammation activity grading

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.

LI Qing-xin, YIN Qing, GUAN Ying-qi, SHAO Chun-hong. The correlationship between Helicobacter pylori infection and autoimmune liver disease[J]. Chinese Hepatolgy, 2023, 28(5): 590-592.

参考文献

[1] Muñoz-Sánchez G, Pérez-Isidro A, Ortiz de Landazuri I, et al. Working algorithms and detection methods of autoantibodies in autoimmune liver disease: A nationwide study. Diagnostics (Basel), 2022, 12(3):697.
[2] van Beers JJBC, Koek GH, Damoiseaux JGMC. The role of autoantibodies in the diagnosis of autoimmune liver disease: Lessons learned from clinical practice. J Appl Lab Med, 2022, 7(1):259-267.
[3] 马雄, 王绮夏. 自身免疫性肝病的研究现状. 中华传染病杂志, 2020, 38(8): 465-467.
[4] Czaja AJ. Nature and implications of oxidative and nitrosative stresses in autoimmune hepatitis. Dig Dis Sci, 2016, 61(10):2784-2803.
[5] 杨秋瑾, 郑杰, 杨婧, 等. 幽门螺杆菌感染对非酒精性脂肪性肝病及其相关结直肠息肉的影响研究. 中国全科医学, 2021, 24(30): 3855-3862.
[6] Zhang FM, Yu CH, Chen HT, et al. Helicobacter pylori infection is associated with gallstones: Epidemiological survey in China. World J Gastroenterol, 2015, 21(29):8912-8919.
[7] Sebode M, Hartl J, Vergani D, et al. Autoimmune hepatitis: From current knowledge and clinical practice to future research agenda. Liver Int, 2018, 38(1):15-22.
[8] Alfano AM, Romito A, Marchese C, et al. Diagnostic accuracy of two tests for determination of anti-m2 in the diagnosis of primary biliary cirrhosis: Is it possible to predict the course of the disease?. Immunol Res, 2017, 65(1):299-306.
[9] Liao R, Fu YP, Wang T, et al. Metavir and FIB-4 scores are associated with patient prognosis after curative hepatectomy in hepatitis B virus-related hepatocellular carcinoma: a retrospective cohort study at two centers in China. Oncotarget, 2017, 8(1):1774-1787.
[10] Panasiuk A, Prokopowicz D, Zak J. Peripheral blood T, B lymphocytes and NK cells in primary biliary cirrhosis. Rocz Akad Med Bialymst, 2001, 46:231-239.
[11] Utiyama SR, Zenatti KB, Nóbrega HA, et al. Rheumatic disease autoantibodies in autoimmune liver diseases. Immunol Invest, 2016, 45(6):566-573.
[12] Vuerich M, Wang N, Kalbasi A, et al. Dysfunctional immune regulation in autoimmune hepatitis: From pathogenesis to novel therapies. Front Immunol, 2021, 12:746436.
[13] 温小凤, 蒋忠胜, 陈念, 等. 慢性乙型肝炎患者幽门螺杆菌感染与肝组织病理的关系, 临床肝胆病杂志, 2015, 31(12): 2051-2053.
[14] Tanaka A, Mori M, Matsumoto K, et al. Increase trend in the prevalence and male-to-female ratio of primary biliary cholangitis, autoimmune hepatitis, and primary sclerosing cholangitis in Japan. Hepatol Res, 2019, 49(8):881-889.
[15] Akulkina LA, Brovko MY, Sholomova VI, et al. Variety of lung involvement in autoimmune liver diseases. Ter Arkh, 2018, 90(8):107-112.