Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 283-291
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.283
Autoantibodies in Chinese patients with chronic hepatitis B: Prevalence and clinical associations
Bo-An Li, Jia Liu, Jun Hou, Jie Tang, Jian Zhang, Jun Xu, Yong-Ji Song, Ai-Xia Liu, Jing Zhao, Jing-Xia Guo, Lin Chen, Han Wang, Li-Hua Yang, Jie Lu, Yuan-Li Mao
Bo-An Li, Jia Liu, Jun Hou, Jian Zhang, Jun Xu, Yong-Ji Song, Ai-Xia Liu, Jing Zhao, Jing-Xia Guo, Lin Chen, Han Wang, Li-Hua Yang, Yuan-Li Mao, Center of Clinical Laboratory Medicine, 302 Military Hospital of China, Beijing 100039, China
Jie Tang, Jie Lu, EUROIMMUN Medical Diagnostics (China) Co., Ltd., Beijing 100101, China
Author contributions: Mao YL designed the research; Li BA, Liu J and Hou J contributed equally to this work in collecting samples, performing the experiments, and data acquisition and analysis; Zhang J and Xu J refined the experiments and clinical data collection; Li BA and Tang J wrote the paper; Song YJ, Liu AX, Zhao J, Guo JX, Chen L, Wang H, Yang LH and Lu J contributed to manuscript review and critical revisions.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yuan-Li Mao, Professor, Center of Clinical Laboratory Medicine, 302 Military Hospital of China, 100 W 4th Ring Middle Rd, Beijing 100039, China. maoyuanli2013@163.com
Telephone: +86-10-63879628 Fax: +86-10-63879628
Received: March 27, 2014
Peer-review started: March 27, 2014
First decision: May 29, 2014
Revised: July 2, 2014
Accepted: August 13, 2014
Article in press: August 28, 2014
Published online: January 7, 2015
Processing time: 286 Days and 0.3 Hours
Abstract

AIM: To investigate the prevalence of autoantibodies and their associations with clinical features in Chinese patients with chronic hepatitis B (CHB).

METHODS: A total of 325 Chinese patients with CHB were enrolled in this retrospective, hospital-based study. Patients with chronic hepatitis C (CHC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC) were included, with healthy donors acting as controls. A panel of autoantibodies that serologically define AIH and PBC was tested by indirect immunofluorescence assay and line immunoassay. The AIH-related autoantibody profile included homogeneous anti-nuclear antibodies (ANA-H), smooth-muscle antibodies, anti-liver kidney microsome type 1, anti-liver cytosolic antigen type 1, and anti-soluble liver antigen/liver pancreas; the PBC-related antibodies were characterized by ANA-nuclear dots/membranous rim-like, anti-mitochondrial antibodies-M2 (AMA-M2), anti-BPO (recombinant antigen targeted by AMA-M2), anti-Sp100, anti-promyelocytic leukemia protein (anti-PML), and anti-gp210. The dichotomization of clustering was used to unequivocally designate the AIH or PBC profiles for each case. Anti-Ro52 antibodies were also tested.

RESULTS: The prevalence of any autoantibody in CHB amounted to 58.2%, which was similar to the 66.2% prevalence in CHC, significantly higher than the 6.7% in the healthy controls (P < 0.001), and lower than the 100% found in AIH and PBC (P = 0.004 and P < 0.001, respectively). There were more anti-PML and anti-gp210 antibodies among the CHB patients than the CHC patients (11.1% vs 0%, P = 0.003; 12.6% vs 0%, P < 0.001, respectively). The prevalence and titer of AMA, anti-BPO, anti-PML, and anti-gp210 were higher in PBC than in those with CHB. Among the CHB patients, the prevalence of ANA, especially ANA-H, was significantly lower in patients with compensated and decompensated cirrhosis compared with patients without cirrhosis. Thirty-eight cases of hepatocellular carcinoma (HCC) in CHB showed a significant difference compared with non-HCC patients in the prevalence of anti-PML (0% vs 12.5%, P = 0.013). Dichotomization of the autoantibodies revealed that the PBC profile was more prevalent in patients with CHB than in those with CHC, and that it was strongly correlated with both compensated and decompensated cirrhosis. In contrast, the prevalence of the AIH profile was significantly higher in non-cirrhosis patients with CHB than in those with compensated cirrhosis (18.5% vs 8.2%, P = 0.039). Moreover, the AIH profile was also closely associated with hepatitis B e-antigen positivity.

CONCLUSION: ANA-H could be an indicator of early-stage CHB. Dichotomizing the autoantibody profiles revealed that the PBC profile is strongly associated with cirrhosis in CHB.

Keywords: Autoantibodies; Chronic hepatitis B; Autoimmune hepatitis; Primary biliary cirrhosis; Cirrhosis; Hepatocellular carcinoma

Core tip: We investigated the prevalence of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC)-related autoantibodies and their associations with clinical features in Chinese patients with chronic hepatitis B. Interestingly, and unexpectedly, we demonstrated that anti-nuclear antibodies (ANA), especially ANA-H, were significantly negatively associated with cirrhosis. Another interesting finding was that the prevalence of anti-promyelocytic leukemia protein antibodies was significantly different between hepatocellular carcinoma (HCC) (0%) and non-HCC patients (12.5%). In terms of analytic methods, for the first time we used an unequivocal dichotomy to cluster the autoantibodies into AIH and PBC profiles to delineate the bias of autoantibody expression for each case. The data showed that the PBC profile was strongly associated with cirrhosis.