原发性胆汁性胆管炎患者甲状腺激素及抗体的临床意义研究

doi:10.12114/j.issn.1007-9572.2019.00.249

摘要/Abstract

摘要： 背景　自身免疫性肝病患者可伴有肝外自身免疫性疾病，以自身免疫性甲状腺疾病（AITD）最为常见。在原发性胆汁性胆管炎（PBC）患者中，肝外自身免疫性疾病的发生率可高达42.3%，研究PBC患者甲状腺激素及抗体的特点或可为PBC的诊断及病情评估提供依据。目的　分析PBC患者甲状腺激素及抗体的临床意义，为PBC的早期诊断及治疗提供依据。方法　回顾性选取2013年6月—2018年7月于西南医科大学附属医院住院的PBC患者121例。其中进展为肝硬化者65例（肝功能分级：Child-Pugh A级39例、Child-Pugh B级19例、Child-Pugh C级7例），未进展为肝硬化者56例。选取同期于西南医科大学附属医院体检的健康者101例。收集PBC患者和健康者一般资料、甲状腺激素及抗体指标。比较PBC患者与健康者，肝硬化患者、非肝硬化患者、健康者，不同肝功能分级肝硬化患者甲状腺激素及抗体指标。结果　PBC患者游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）水平低于健康者，促甲状腺激素（TSH）水平及甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TGAb）阳性率高于健康者（P<0.05）。非肝硬化患者、肝硬化患者FT3、FT4水平低于健康者，TSH水平及TPOAb、TGAb阳性率高于健康者（P<0.05）；肝硬化患者FT3、FT4水平及TGAb阳性率低于非肝硬化患者，TSH水平高于非肝硬化患者（P<0.05）。Child-Pugh B级、Child-Pugh C级肝硬化患者FT3水平低于Child-Pugh A级患者，TSH水平高于Child-Pugh A级患者（P<0.05）；Child-Pugh C级肝硬化患者FT4水平低于Child-Pugh A级患者（P<0.05）；Child-Pugh C级肝硬化患者FT3、FT4水平低于Child-Pugh B级肝硬化患者，TSH水平高于Child-Pugh B级肝硬化患者（P<0.05）。结论　PBC患者的甲状腺激素及抗体与健康者存在差别；发生肝硬化的PBC患者FT3、FT4水平降低，TSH水平升高，提示TSH可能有一定促肝纤维化作用，而FT3、FT4在PBC患者肝纤维化进展中可能存在负性作用；在PBC肝硬化患者中，FT3水平随PBC患者肝功能分级升高而升高，TSH水平随PBC患者肝功能分级升高而降低，FT3、TSH水平侧面反映了肝功能损害程度。

关键词: 胆管炎；肝硬化, 胆汁性；甲状腺激素类；甲状腺球蛋白；碘化物过氧化物酶

Abstract: Background　Patients with autoimmune liver disease may be accompanied by extrahepatic autoimmune disease，and autoimmune thyroid disease（AITD）is the most common.In primary biliary cholangitis（PBC）patients，the incidence of extrahepatic autoimmune disease can be up to 42.3%.The study of thyroid hormone and antibody secretion in patients with PBC may provide evidence for the diagnosis and evaluation of PBC.Objective　To analyze the clinical significance of thyroid hormones and antibodies in patients with PBC，offering evidence for early diagnosis and treatment of PBC.Methods　We conducted a retrospective study among 121 PBC inpatients from the Affiliated Hospital of Southwest Medical University from June 2013 to July 2018，among whom 65 progressed to cirrhosis（Child-Pugh grade：39 cases of grade A，19 cases of grade B，7 cases of grade C）and other 56 did not.A total of 101 healthy physical examinees were selected from the hospital during the same period.General data，thyroid hormone and antibody indices were collected.Thyroid hormone and antibody were compared between PBC patients and healthy people，cirrhosis patients and non-cirrhosis patients and healthy people，cirrhosis patients with different liver function grades. Results　 Compared with the healthy controls，lower average levels of FT3 and FT4，and higher average level of TSH as well as higher rates of TPOAb and TGAb positivity were found in PBC patients（P<0.05），and in cirrhosis patients and non-cirrhosis patients（P<0.05）．Cirrhosis patients had lower average levels of FT3 and FT4，and lower rate of TGAb positivity，but higher average level of TSH than non-cirrhosis patients（P<0.05）．Compared with those with grade B or C cirrhosis，patients with grade A cirrhosis showed higher average level of FT3 and lower average level of TSH（P<0.05）．The average level of FT4 in those with grade C cirrhosis was lower than that of those with grade A cirrhosis（P<0.05）．Patients with grade C cirrhosis showed lower average levels of FT3 and FT4，and higher average level of TSH than those with grade B cirrhosis（P<0.05）．Conclusion　There are differences in thyroid hormones and antibodies between PBC patients and healthy subjects.Decreased levels of FT3 and FT4 and elevated level of TSH in PBC patients with cirrhosis indicate that TSH may play a role in promoting hepatic fibrosis，but FT3 and FT4 may be involved in delaying the progression.The level of FT3 increases with the increase of Child-Pugh grade while the level of TSH decreases with that in PBC patients.The levels of FT3 and TSH reflect the severity of liver function impairment indirectly.

Key words: Cholangitis；Liver cirrhosis, biliary；Thyroid hormones；Thyroglobulin；Iodide peroxidase

张亚军,郭小敏,蒋玉凤. 原发性胆汁性胆管炎患者甲状腺激素及抗体的临床意义研究[J]. 中国全科医学, 2019, 22(33): 4064-4068. DOI: 10.12114/j.issn.1007-9572.2019.00.249.
ZHANG Yajun,GUO Xiaomin,JIANG Yufeng. Clinical Significance of Thyroid Hormones and Antibodies in Patients with Primary Biliary Cholangitis　[J]. Chinese General Practice, 2019, 22(33): 4064-4068. DOI: 10.12114/j.issn.1007-9572.2019.00.249.

参考文献

［1］中华医学会肝病学分会，中华医学会消化病学分会，中华医学会感染病学分会.原发性胆汁性肝硬化（又名原发性胆汁性胆管炎）诊断和治疗共识（2015）［J］．中华肝脏病杂志，2016，24（1）：5-13．DOI：10.3760/cma.j.issn.1007-3418.2016.01.004.
［2］SELMI C，MAYO M J，BACH N，et al．Primary biliary cirrhosis in monozygotic and dizygotic twins：genetics，epigenetics，and environment［J］．Gastroenterology，2004，127（2）：485-492.
［3］赵家军.甲状腺疾病与肝脏［J］．中华肝脏病杂志，2014，22（3）：165-167．DOI：10.3760/cma.j.issn.1007-3418.2014.03.002.
ZHAO J J.The relationship between thyroid dysfunction and liver［J］．Chinese Journal of Hepatology，2014，22（3）：165-167．DOI：10.3760/cma.j.issn.1007-3418.2014.03.002.
［4］LINDOR K D，GERSHWIN M E，POUPON R，et al．Primary biliary cirrhosis［J］．Hepatology，2009，50（1）：291-308．DOI：10.1002/hep.22906.
［5］中国中西医结合学会消化系统疾病专业委员会.肝硬化中西医结合诊疗共识［J］．中国中西医结合消化杂志，2011，19（4）：277-279．DOI：10.3969/j.issn.1671-038X.2011.04.025.
［6］MURATORI P，FABBRI A，LALANNE C，et al．Autoimmune liver disease and concomitant extrahepatic autoimmune disease［J］．Eur J Gastroenterol Hepatol，2015，27（10）：1175-1179．DOI：10.1097/MEG.0000000000000424.
［7］SILVEIRA M G，MENDES F D，DIEHL N N，et al．Thyroid dysfunction in primary biliary cirrhosis，primary sclerosing cholangitis and non-alcoholic fatty liver disease［J］．Liver Int，2009，29（7）：1094-1100．DOI：10.1111/j.1478-3231.2009.02003.x.
［8］SUZUKI Y，ISHIDA K，TAKAHASHI H，et al．Primary biliary cirrhosis associated with Graves' disease in a male patient［J］．Clin J Gastroenterol，2016，9（2）：99-103．DOI：10.1007/s12328-016-0635-x.
［9］SELMI C，MEDA F，KASANGIAN A，et al．Experimental evidence on the immunopathogenesis of primary biliary cirrhosis［J］．Cell Mol Immunol，2010，7（1）：1-10．DOI：10.1038/cmi.2009.104.
［10］CZAJA A J.Autoantibodies as prognostic markers in autoimmune liver disease［J］．Dig Dis Sci，2010，55（8）：2144-2161．DOI：10.1007/s10620-010-1268-4.
［11］PETTA S，MAZZOLA A，GRIMAUDO S，et al．919 thyroid-stimulating hormone serum level，liver thyroid-stimulating hormone-receptor，and severe fibrosis in genotype 1 chronic hepatitis C patients with normal thyroid function［J］．Journal of Hepatology，2012，56：S358．DOI：10.1016/s0168-8278（12）60931-3.
［12］HASSAN M M，KASEB A，LI D H，et al．Association between hypothyroidism and hepatocellular carcinoma：a case-control study in the United States［J］．Hepatology，2009，49（5）：1563-1570．DOI：10.1002/hep.22793.
［13］PERRA A，KOWALIK M A，PIBIRI M，et al．Thyroid hormone receptor ligands induce regression of rat preneoplastic liver lesions causing their reversion to a differentiated phenotype［J］．Hepatology，2009，49（4）：1287-1296．DOI：10.1002/hep.22750.