Zhao Dan-Tong, Liu Yan-Min, Han Ying, Zhang Hai-Ping, Zhao Yan, Yan Hui-Ping
Clinical Research Center for Autoimmune Liver Disease & Clinical Laboratory Center.
Department of Liver Disease Immunology, Beijing You'an Hospital, Capital Medical University, Beijing, China.
Medicine (Baltimore). 2020 Jan;99(3):e18856. doi: 10.1097/MD.0000000000018856.
Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease. It is often associated with extrahepatic autoimmune disorders. However, the concurrence of PBC and Sjögren syndrome (SS) with the subsequent onset of autoimmune hemolytic anemia (AIHA) is extremely rare.
This study investigated a 60-year-old woman admitted to our hospital with complaints of xerostomia for 5 years, pruritus for 3 years, and abnormal liver function for 3 months.
The patient was suffering from typical clinical PBC and SS, and developed decompensated liver cirrhosis after 32 months of ursodeoxycholic acid (UDCA) therapy. In May 2018, she was readmitted to the hospital with a high fever of 39 °C, coughing, and sever fatigue without remission after 3 days of cephalosporin antibiotic therapy. During the clinical course of PBC, her antimitochondrial antibodies (AMA) titers fluctuated from 1:1000 to negative and then to weakly positive, determined by indirect immunofluorescence (IIF), immunoblotting, and enzyme-linked immunosorbent assay (ELISA) based on recombinant mitochondrial antigens; furthermore, her titers of anti-gp210, an antinuclear antibody (ANA), increased sharply. Laboratory tests and imaging were performed to diagnose PBC and SS in September 2015. However, she was subsequently diagnosed with AIHA after 32 months of UDCA therapy based on the identification of pancytopenia, increased reticulocyte (RET) count, and a positive result from the direct Coombs test.
UDCA, hepatic protectant, albumin infusion, chest drainage, rational antibiotic use, diuretics, and methylprednisolone were used to treat the patient.
Liver cirrhosis was complicated by the development of AIHA, which became severe at 42 months of follow-up.
This is the first case report showing a patient with comorbid PBC and SS, as well as the sequential development of AIHA with decreased AMA and increased anti-gp210 titers; this may have been due to immunodeficiency. These findings stress the importance of the serological screening of ANA profile, as well as repeated measurement of ANA and AMA to track PBC progression and prognosis.
原发性胆汁性胆管炎（PBC）是一种罕见的自身免疫性胆汁淤积性肝病。它常与肝外自身免疫性疾病相关。然而，PBC与干燥综合征（SS）并发并随后发生自身免疫性溶血性贫血（AIHA）的情况极为罕见。
本研究调查了一名60岁女性，因口干5年、瘙痒3年、肝功能异常3个月入院。
该患者患有典型的临床PBC和SS，在接受熊去氧胆酸（UDCA）治疗32个月后发展为失代偿期肝硬化。2018年5月，她因高热39℃、咳嗽和严重疲劳再次入院，在接受头孢菌素抗生素治疗3天后症状无缓解。在PBC的临床过程中，通过基于重组线粒体抗原的间接免疫荧光法（IIF）、免疫印迹法和酶联免疫吸附测定（ELISA）测定，她的抗线粒体抗体（AMA）滴度从1:1000波动至阴性，然后又变为弱阳性；此外，她的抗核抗体（ANA）抗gp210滴度急剧升高。2015年9月进行了实验室检查和影像学检查以诊断PBC和SS。然而，在UDCA治疗32个月后，基于全血细胞减少、网织红细胞（RET）计数增加以及直接抗人球蛋白试验阳性，她随后被诊断为AIHA。
使用UDCA、肝保护剂、输注白蛋白、胸腔引流、合理使用抗生素、利尿剂和甲泼尼龙对患者进行治疗。
肝硬化并发AIHA，在随访42个月时病情加重。
这是首例报告显示患者同时患有PBC和SS，以及AIHA的相继发生，同时AMA降低和抗gp特异性抗体210滴度升高；这可能是由于免疫缺陷所致。这些发现强调了血清学筛查ANA谱以及重复测量ANA和AMA以追踪PBC进展和预后的重要性。
