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. 2018 Jun;46(3):385-393.
doi: 10.1007/s15010-018-1136-2. Epub 2018 Mar 29.

Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT

Linlin Yan  1 , Yongqiong Deng  1   2 , Jiyuan Zhou  1 , Hong Zhao  1 , Guiqiang Wang  3   4   5 ; China HepB-Related Fibrosis Assessment Research Group
Collaborators, Affiliations

Serum YKL-40 as a biomarker for liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT

Linlin Yan et al. Infection. 2018 Jun.

Abstract

Purpose: YKL-40 is a chitinase-like protein expressed in multiple tissues including liver and is reported as a fibrosis marker. This study aimed to determine whether YKL-40 could serve as a diagnostic marker for the assessment of liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT.

Methods: Six hundred and eighty-five patients with chronic hepatitis B infection were enrolled in this study from October 2013 to March 2016. All patients underwent liver biopsy and then staged based on Ishak histological system. Serum YKL-40 levels were measured by Human Magnetic Luminex Assays.

Results: Among chronic hepatitis B patients with normal and mildly elevated ALT, almost more than 30% of patients have significant liver fibrosis. Serum YKL-40 levels increased significantly in parallel with the progression of fibrosis in patients with ALT less than two times the upper limit of normal range (P < 0.0001). Multivariate analysis revealed that serum YKL-40, hyaluronic acid, PLT, and AST were independently associated with significant fibrosis. We established a novel YKL-40-based fibrosis model for patients with ALT less than two times the upper limit of normal range (ULN). YKL-40 model was superior to APRI, FIB-4, Forns' index, and Hui model for diagnosis of significant fibrosis in patients with ALT < 2ULN, with AUROCs of 0.786 [95% confidence interval (CI) 0.726-0.846] in the training group, 0.831 (95%CI 0.752-0.910) in the validation group and 0.801 (95%CI 0.753-0.849) in the entire cohort.

Conclusion: Serum YKL-40 is a feasible biomarker of liver fibrosis in chronic hepatitis B patients. YKL-40 model was superior to APRI, FIB-4, Forns' index and Hui model for diagnosis of significant fibrosis in patients with normal and mildly elevated ALT.

Keywords: Chronic hepatitis B; Liver fibrosis; YKL-40.

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Conflict of interest statement

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

This study was approved by the local ethics committee of Peking University First Hospital.

Figures

Fig. 1
Fig. 1
Proportion of patients with significant fibrosis in the group of G1–G5 in chronic hepatitis B patients. Patients with a normal ALT and b mildly elevated ALT
Fig. 2
Fig. 2
Associations between serum YKL-40 levels and liver fibrosis. a YKL-40 in total patients, b YKL-40 in patients with ALT < 2 × ULN. P < 0.0001 for all fibrosis stags. ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05
Fig. 3
Fig. 3
Receiver operating characteristic curve (ROC) analysis showing the diagnostic performance of noninvasive models for significant fibrosis. Area under the ROC curves (AUROCs) of YKL-40 model, ARPI, FIB4, Forns’ index and Hui model in the diagnosis of significant fibrosis in CHB patients with ALT < 2ULN. a Training group and b validation group
See this image and copyright information in PMC

References

    1. Sorrell MF, Belongia EA, Costa J, Gareen IF, Grem JL, Inadomi JM, et al. National institutes of health consensus development conference statement: management of hepatitis B. Ann Intern Med. 2009;150:104–110. doi: 10.7326/0003-4819-150-2-200901200-00100. - DOI - PubMed
    1. Cui Y, Jia J. Update on epidemiology of hepatitis B and C in China. J Gastroenterol Hepatol. 2013;28:7–10. doi: 10.1111/jgh.12220. - DOI - PubMed
    1. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–662. doi: 10.1002/hep.23190. - DOI - PubMed
    1. Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–561. doi: 10.1007/s12072-012-9365-4. - DOI - PubMed
    1. Tsang PS, Trinh H, Garcia RT, Phan JT, Ha NB, Nguyen H, et al. Significant prevalence of histologic disease in patients with chronic hepatitis B and mildly elevated serum alanine aminotransferase levels. Clin Gastroenterol Hepatol. 2008;6:569–574. doi: 10.1016/j.cgh.2008.02.037. - DOI - PubMed

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