Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2023; 29(34): 5075-5081
Published online Sep 14, 2023. doi: 10.3748/wjg.v29.i34.5075
Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis
Yu-Jin Zhu, Jing Li, Yong-Gang Liu, Yong Jiang, Xiao-Jing Cheng, Xu Han, Chun-Yan Wang, Jia Li
Yu-Jin Zhu, Jing Li, Graduate School, Tianjin Medical University, Tianjin 300041, China
Yong-Gang Liu, Department of Pathology, Clinical School of the Second People's Hospital, Tianjin 300110, China
Yong Jiang, Department of Gastroenterology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
Xiao-Jing Cheng, Xu Han, Chun-Yan Wang, Jia Li, Department of Gastroenterology, Clinical School of the Second People's Hospital, Tianjin 300110, China
Author contributions: Zhu YJ wrote the manuscript; Zhu YJ, Cheng XJ, and Han X contributed to data collation; Zhu YJ and Li J contributed to statistical analysis; Liu YG contributed to liver pathology reading; Jiang Y, Wang CY, and Li J contributed to manuscript revision; Wang CY and Li J contributed to research supervision; Wang CY contributed to project design.
Institutional review board statement: The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the local Ethics Committee (Clinical School of the Second People's Hospital of Tianjin).
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors have no conflict of interest to disclose.
Data sharing statement: The data underlying this article can be available in this article and in its online supplementary material or from the first author.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chun-Yan Wang, Doctor, Chief Doctor, Department of Gastroenterology, Clinical School of the Second People's Hospital, No. 7 Sudi South Road, Nankai District, Tianjin 300110, China. wangchunyan123@tmu.edu.cn
Received: June 4, 2023
Peer-review started: June 4, 2023
First decision: June 21, 2023
Revised: July 15, 2023
Accepted: August 25, 2023
Article in press: August 25, 2023
Published online: September 14, 2023
Abstract
BACKGROUND

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.

AIM

To explore the clinical characteristics of early-stage PBC, identify PBC in the early clinical stage, and promptly treat and monitor PBC.

METHODS

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.

RESULTS

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 vs stage III vs stage IV, P < 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 (P < 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 (P < 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 (P < 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 (P < 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%).

CONCLUSION

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.

Keywords: Primary biliary cholangitis, Early stage, Biochemical makers, Autoantibodies, Pathology

Core Tip: This is a retrospective study of the characteristics of early-stage primary biliary cholangitis (PBC) patients, in which we found the suggestive role of γ-glutamyl transferase as an indicator of cholestasis in the early diagnosis of PBC. We also found that when anti-mitochondria antibody (AMA) and AMA-M2 were negative, positivity for anti-nuclear antibody (ANA) especially ANA centromere indicates early-stage PBC.