Angiopoietin-like protein as a novel marker for liver fibrosis in chronic hepatitis B patients with normal to minimally raised ALT

Yongqiong Deng, Hong Zhao, Jiyuan Zhou, Linlin Yan, Guiqiang Wang, China HepB-Related Fibrosis Assessment Research Group, Yongqiong Deng, Hong Zhao, Jiyuan Zhou, Linlin Yan, Guiqiang Wang, China HepB-Related Fibrosis Assessment Research Group

Abstract

Background: For hepatitis B patients who do not meet the treatment criteria recommended by guidelines, therapy decisions depend on hepatic histology. Angiopoietin-like protein 2 (Angptl2) is a mediator of chronic inflammation that contributes to extracellular matrix remodeling. The aim of this study was to explore the predictive value of Angptl2 as a novel biomarker of liver histology.

Methods: Hepatitis B patients with normal to minimally raised ALT were recruited. Serum Angptl2 concentrations were detected using commercial ELISA kit. The fibrosis score were assessed according to Ishak criteria. Significant fibrosis was defined as ISHAK score ≥ 3.

Results: Of 460 patients, 223 cases served as training cohort and 237 ones as validation cohort. Serum Angptl2 concentration was significantly associated with fibrosis scores in both training and validation group. Angptl2 combined index (ACI) for assessing significant fibrosis was developed from training cohort, based on Angptl2 and conventional variables. ACI showed areas under receiver-operating characteristic curve (AUC) of 0.835 for predicting significant fibrosis, which was superior to APRI (AUC = 0.776, P = 0.049), FIB-4 (AUC = 0.750, P = 0.010), Hui model (AUC = 0.756, P = 0.028), and had a better trend than Forn's index (AUC = 0.796, P = 0.083) in training cohort. Finally, validation cohort revealed its robustness and reliability.

Conclusion: Higher Angptl2 level represents as a potential biomarker independently associated with fibrosis stages. Compared with APRI, Hui model, FIB-4, Forn's index, ACI did better in diagnosing significant fibrosis in hepatitis B patients.

Trial registration: The complete clinical trials protocol is available by request at clinicaltrials.gov ( NCT01962155 ) and chictr.org ( ChiCTR-DDT-13003724 ).

Keywords: Angiopoietin-like protein; Hepatitis B; Liver fibrosis.

Conflict of interest statement

Ethics approval and consent to participate

All patients provided written informed consent for the scientific use of their data and samples, and the study was approved by the Ethical Committee of Peking University First Hospital.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Boxplot of the serum Angptl2 concentrations in relation to fibrosis score in the training cohort all patients (a) and patients with normal ALT (b) .The above and below lines indicate the SD. The middle line represents the medians. *** p < 0.001, **p < 0.01, and *p < 0.05. For all patients in the training cohort, p < 0.001. For patients with normal ALT in the training cohort, p = 0.003
Fig. 2
Fig. 2
Receiver operating characteristics (ROC) cures of the Angptl2 combined index (ACI), APRI, FIB-4, Forns’ index to distinguish patients with and without significant fibrosis in the Training cohort. a Area under the ROC curves (AUC) of above models in the training set. b AUC for above models in patients with Normal ALT in the training set
Fig. 3
Fig. 3
Receiver-operating characteristic curve (ROC) cures of the ACI, APRI, FIB-4, Forns’ index to distinguish patients with and without significant fibrosis in the Validation cohort. (a) AUC of above models in the validation set. (b) AUC of above models in patients with normal ALT in validation set

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