Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2017; 23(36): 6705-6714
Published online Sep 28, 2017. doi: 10.3748/wjg.v23.i36.6705
Serum angiotensin-converting enzyme level for evaluating significant fibrosis in chronic hepatitis B
Ryuichi Noguchi, Kosuke Kaji, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Hideto Kawaratani, Yasushi Okura, Yosuke Aihara, Masanori Furukawa, Akira Mitoro, Hitoshi Yoshiji
Ryuichi Noguchi, Kosuke Kaji, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Hideto Kawaratani, Yasushi Okura, Yosuke Aihara, Masanori Furukawa, Akira Mitoro, Hitoshi Yoshiji, Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan
Author contributions: Noguchi R and Kaji K contributed equally to this work; Noguchi R and Kaji K collected and analyzed the data, and drafted the manuscript; Namisaki T, Moriya K, Kitade M, Takeda T, Kawaratani H, Okura Y, Aihara Y, Furukawa M and Mitoro A offered the technical or material support; Yoshiji H designed and supervised the study; all authors have read and approved the final version to be published.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Nara Medical University (Nara, Japan; Approval number 1077).
Informed consent statement: Waiver of informed consent for all study participants was guaranteed by information disclosure on website (http://www.naramed-u.ac.jp/~3int/kenkyu.html).
Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this paper.
Data sharing statement: Informed consent for data sharing was not obtained but the presented data are anonymized and risk of identification is low.
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: Kosuke Kaji, MD, PhD, Third Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. kajik@naramed-u.ac.jp
Telephone: +81-744-223051 Fax: +81-744-247122
Received: March 22, 2017
Peer-review started: March 23, 2017
First decision: April 21, 2017
Revised: May 1, 2017
Accepted: June 18, 2017
Article in press: June 19, 2017
Published online: September 28, 2017
Processing time: 186 Days and 12 Hours
Abstract
AIM

To evaluate the diagnostic performance of angiotensin-converting enzyme (ACE) on significant liver fibrosis in patients with chronic hepatitis B (CHB).

METHODS

In total, 100 patients with CHB who underwent liver biopsy in our hospital were enrolled, and 70 patients except for 30 patients with hypertension, fatty liver or habitual alcoholic consumption were analyzed. We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), the Mac-2 binding protein glycosylation isomer (M2BPGi) level and the number of platelets (Plt).

RESULTS

Serum ACE levels showed moderately positive correlation with liver fibrotic stages (R2 = 0.181). Patients with significant, advanced fibrosis and cirrhosis (F2-4) had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis (F0-1). For significant fibrosis (≥ F2), the 12.8 U/L cut-off value of ACE showed 91.7% sensitivity and 75.0% specificity. The receiver-operating characteristic (ROC) curves analysis revealed that the area under the curve (AUC) value of ACE was 0.871, which was higher than that of APRI, FIB-4, M2BPGi and Plt.

CONCLUSION

The serum ACE level could be a novel noninvasive, easy, accurate, and inexpensive marker of significant fibrosis stage in patients with CHB.

Keywords: Angiotensin-converting enzyme; Hepatitis B virus; Liver fibrosis; Noninvasive fibrosis marker; Aspartate aminotransferase-to-platelet ratio index; Fibrosis index based on four factors; Mac-2 binding protein glycosylation isomer

Core tip: Liver fibrosis is one of key factors to determine therapeutic intervention for patients with chronic hepatitis B (CHB). However, the noninvasive prediction of CHB-related liver fibrosis is difficult. Angiotensin-converting enzyme (ACE) is reportedly involved in liver fibrogenesis. In this paper, we demonstrate that serum ACE levels are elevated in patients with CHB and show the predictive potential to diagnose significant fibrosis (≥ F2), which is the therapeutically adapted stage, with higher accuracy as compared with other fibrotic markers including APRI, FIB-4, M2BPGi and Plt. The serum ACE level could be a novel noninvasive marker of significant fibrosis stage in CHB.