Case Control Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2018; 24(37): 4272-4280
Published online Oct 7, 2018. doi: 10.3748/wjg.v24.i37.4272
Evaluation of elastography combined with serological indexes for hepatic fibrosis in patients with chronic hepatitis B
Bin Xu, Ning-Ming Zhou, Wei-Tian Cao, Xiao-Jing Li
Bin Xu, Ning-Ming Zhou, Wei-Tian Cao, Department of ultrasound, Fudan University affiliated Shanghai fifth people’s hospital, Shanghai 200240, China
Xiao-Jing Li, Department of pathology, Fudan University affiliated Shanghai fifth people’s hospital, Shanghai 200240, China
Author contributions: Xu B designed research; Xu B, Cao WT, Li XJ performed research; Zhou NM contributed new reagents or analytic tools; Li XJ analyzed data; Xu B wrote the paper.
Supported by the Natural Science Research Project of Minhang District, No. 2013MHZ003.
Institutional review board statement: The study was approved by the ethics committee of Fudan University affiliated Shanghai fifth people’s hospital.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Data are available from the corresponding author at
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:
Correspondence to: Ning-Ming Zhou, MD, Chief Doctor, Department of ultrasound, Fudan University affiliated Shanghai fifth people’s hospital, 128 Ruili road, Minhang district, Shanghai 200240, China.
Telephone: +86-21-24289356 Fax: +86-21-24289356
Received: June 22, 2018
Peer-review started: June 22, 2018
First decision: July 25, 2018
Revised: August 6, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: October 7, 2018
Research background

Pathological examination is known to be the gold standard for diagnosing liver fibrosis, as it enables a clear diagnosis of liver fibrosis grading. However, pathological examination is an invasive examination and cannot be used as a screening tool. At present, the degree of liver fibrosis is mainly evaluated by serological indicators in the clinic, however the accuracy is relatively low. With advances in technology, ultrasound elastography can be used to assess liver tissue stiffness, although the accuracy is not high. Therefore, it is necessary to explore reliable methods for diagnosing liver fibrosis and assessing the degree of liver fibrosis.

Research motivation

The motivation of this study is to find a more suitable method for the combined diagnosis of liver fibrosis and to establish an optimal non-invasive model for assessing the severity of liver fibrosis. This will provide a reference for non-invasive screening of liver fibrosis.

Research objectives

This study enrolled patients with chronic hepatitis B (CHB) as the research subjects. The aim of this study is to analyze serum markers and ultrasound elastography indicators for diagnosing liver fibrosis and liver fibrosis grading based on pathological results.

Research methods

According to the results of liver biopsy, 338 patients with CHB admitted to our hospital were divided into a diseased group and control group. The diseased group continued to be divided into four groups according to the degree of fibrosis. General data, shear wave velocity (SWV), and serological markers were compared between the two groups. Further independent risk factors for liver fibrosis in patients were analyzed by logistic regression. The accuracy of different indicators in diagnosing liver fibrosis was compared by receiver operating characteristic (ROC) curves. The correlation between different fiber levels and serum indicators or elastography indicators was analyzed. Finally, a multivariate linear regression was used to establish a mathematical model for assessing the severity of liver fibrosis with elastography combined with serological markers.

Research results

SWV, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), hyaluronic acid (HA), type-IV collagen (CIV), aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the 4 factor (FIB-4) were significantly higher in the disease group than in the control group (P < 0.05). The multivariate logistic regression analysis results revealed that SWV, HA, CIV and APRI significantly affected the occurrence of hepatic fibrosis. The ROC curve revealed that the accuracy of the diagnosis of hepatic fibrosis for SWV and HA were 87.3% and 84.8%, respectively. The accuracy of SWV combined with HA was 88.9%. Spearman correlation analysis revealed that hepatic fibrosis was positively correlated with SWV, AST/ALT, HA, CIV, APRI and FIB-4 levels. The R values were 0.767, 0.684, 0.711, 0.681, 0.634 and 0.702, respectively, and the difference was statistically significant (all P < 0.05). The multiple linear regression analysis revealed that SWV, AST/ALT, HA, CIV, APRI and FIB-4 were screened as statistically significant independent factors. The established model was: fibrosis level = -4.046 + 1.024 × SWV + 1.170 × AST/ALT + 0.011 × HA + 0.020 × CIV + 0.719 × APRI + 0.379 × FIB-4.

Research conclusions

SWV can non-invasively and effectively diagnose liver fibrosis. SWV combined with serological indicators can further improve the accuracy of diagnosing liver fibrosis. The multiple linear regression equation established by SWV combined with serological indicators is expected to be a non-invasive tool for assessing the degree of liver fibrosis.

Research perspectives

This study is a single-center study, and the sample size is limited and insufficient to fully guarantee the reliability of the study. Therefore, the equation we established cannot be used as an accurate tool for clinical prediction of lymph node metastasis, but it is worthy of further clinical validation and promotion. In addition, for serological indicators that can reflect the degree of liver fibrosis, we can further consult the literature to explore the mechanism of the degree of fibrosis. This would help us understand the diagnostic significance of serological markers with respect to the degree of liver fibrosis.