Graduate School, Tianjin Medical University, Tianjin 300041, China.
Department of Pathology, Clinical School of the Second People's Hospital, Tianjin 300110, China.
World J Gastroenterol. 2023 Sep 14;29(34):5075-5081. doi: 10.3748/wjg.v29.i34.5075.
Primary biliary cholangitis (PBC) is a chronic progressive autoimmune cholestatic disease. The main target organ of PBC is the liver, and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis.
To explore the clinical characteristics of early-stage PBC, identify PBC in the early clinical stage, and promptly treat and monitor PBC.
The data of 82 patients with PBC confirmed by pathology at Tianjin Second People's Hospital from January 2013 to November 2021 were collected, and the patients were divided into stage I, stage II, stage III, and stage IV according to the pathological stage. The general data, serum biochemistry, immunoglobulins, and autoimmune antibodies of patients in each stage were retrospectively analyzed.
In early-stage (stages I + II) PBC patients, 50.0% of patients had normal alanine aminotransferase (ALT) levels, and 37.5% had normal aspartate aminotransferase (AST) levels. For the remaining patients, the ALT and AST levels were mildly elevated; all of these patients had levels of < 3 times the upper limit of normal values. The AST levels were significantly different among the three groups (stages I + II stage III stage IV, < 0.05). In the early stage, 29.2% of patients had normal alkaline phosphatase (ALP) levels. The remaining patients had different degrees of ALP elevation; 6.3% had ALP levels > 5 times the upper limit of normal value. Moreover, γ-glutamyl transferase (GGT) was more robustly elevated, as 29.2% of patients had GGT levels of > 10 times the upper limit of normal value. The ALP values among the three groups were significantly different ( < 0.05). In early stage, the jaundice index did not increase significantly, but it gradually increased with disease progression. However, the above indicators were significantly different ( < 0.05) between the early-stage group and the stage IV group. With the progression of the disease, the levels of albumin and albumin/globulin ratio tended to decrease, and the difference among the three groups was statistically significant ( < 0.05). In early-stage patients, IgM and IgG levels as well as cholesterol levels were mildly elevated, but there were no significant differences among the three groups. Triglyceride levels were normal in the early-stage group, and the differences among the three groups were statistically significant ( < 0.05). The early detection rates of anti-mitochondria antibody (AMA) and AMA-M2 were 66.7% and 45.8%, respectively. The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC. When AMA and AMA-M2 were negative, in the early stage, the highest autoantibody was anti-nuclear antibody (ANA) (92.3%), and in all ANA patterns, the highest was ANA centromere (38.5%).
In early-stage PBC patients, ALT and AST levels are normal or mildly elevated, GGT and ALP levels are not elevated in parallel, GGT levels are more robustly elevated, and ALP levels are normal in some patients. When AMA and AMA-M2 are negative, ANA especially ANA centromere positivity suggests the possibility of early PBC. Therefore, in the clinic, significantly elevated GGT levels with or without normal ALP levels and with ANA (particularly ANA centromere) positivity (when AMA and AMA-M2 are negative) may indicate the possibility of early PBC.
原发性胆汁性胆管炎(PBC)是一种慢性进行性自身免疫性胆汁淤积性疾病。PBC 的主要靶器官是肝脏,肝内小胆管的非化脓性炎症最终可能发展为肝硬化或肝纤维化。
探讨早期 PBC 的临床特征,识别早期临床阶段的 PBC,并及时进行治疗和监测。
收集 2013 年 1 月至 2021 年 11 月在天津市第二人民医院经病理证实的 82 例 PBC 患者资料,根据病理分期将患者分为Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期。回顾性分析各期患者的一般资料、血清生化、免疫球蛋白和自身抗体。
在早期(Ⅰ+Ⅱ期)PBC 患者中,50.0%的患者丙氨酸氨基转移酶(ALT)水平正常,37.5%的患者天门冬氨酸氨基转移酶(AST)水平正常。对于其余患者,ALT 和 AST 水平轻度升高;所有患者的 ALT 和 AST 水平均<3 倍正常值上限。三组间 AST 水平差异有统计学意义(Ⅰ+Ⅱ期<Ⅲ期<Ⅳ期,<0.05)。早期 29.2%的患者碱性磷酸酶(ALP)水平正常。其余患者的 ALP 水平有不同程度的升高;6.3%的患者 ALP 水平>5 倍正常值上限。此外,γ-谷氨酰转肽酶(GGT)升高更为明显,29.2%的患者 GGT 水平>10 倍正常值上限。三组间 ALP 值差异有统计学意义(<0.05)。早期时,黄疸指数升高不明显,但随着疾病的进展逐渐升高。然而,早期组与Ⅳ期组间差异有统计学意义(<0.05)。随着病情的进展,白蛋白和白蛋白/球蛋白比值呈下降趋势,三组间差异有统计学意义(<0.05)。在早期患者中,IgM 和 IgG 水平以及胆固醇水平轻度升高,但三组间差异无统计学意义。早期组甘油三酯水平正常,三组间差异有统计学意义(<0.05)。抗线粒体抗体(AMA)和 AMA-M2 的早期检出率分别为 66.7%和 45.8%。在Ⅳ期 PBC 患者中,抗 Sp100 抗体的阳性率明显较高。当 AMA 和 AMA-M2 阴性时,在早期阶段,最高的自身抗体是抗核抗体(ANA)(92.3%),在所有 ANA 模式中,最高的是 ANA 着丝粒(38.5%)。
在早期 PBC 患者中,ALT 和 AST 水平正常或轻度升高,GGT 和 ALP 水平不平行升高,GGT 水平升高更为明显,部分患者 ALP 水平正常。当 AMA 和 AMA-M2 阴性时,ANA 尤其是 ANA 着丝粒阳性提示可能为早期 PBC。因此,临床上,显著升高的 GGT 水平伴或不伴正常 ALP 水平和 ANA(尤其是 ANA 着丝粒)阳性(当 AMA 和 AMA-M2 阴性时)可能提示存在早期 PBC 的可能性。