Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease.

Erina Kumagai,Tatsuya Kanto,Masanori Atsukawa,Takuji Torimura,Hideyuki Hyogo,Masashi Mizokami,Sumio Watanabe,Taeang Arai,Masaya Sugiyama,Tsuyoshi Ishida,Tomohiko Ohashi,Sachiyo Yoshio,Kiyoaki Ito,Takumi Kawaguchi,Hirotaka Shoji,Yohei Mano,Kazuaki Chayama,Yuichi Nozaki,Masashi Yoneda,Norio Itokawa,Masaaki Korenaga

doi:10.1038/srep35282

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. YKL-40, chitinase-like protein expressed in multiple tissues including liver, is involved in cell proliferation, inflammation and remodeling of the extracellular matrix. The aim of this study was to assess whether serum YKL-40 levels are associated with liver fibrosis in NAFLD patients. Serum YKL-40 levels were quantified in 111 NAFLD patients and 23 HCC patients with NAFLD. To identify the source of YKL-40, immunofluorescence staining of liver specimens from NAFLD patients was performed. Serum YKL-40 levels in NAFLD patients increased in accordance with the progression of liver fibrosis. Multivariate analysis revealed that YKL-40 was one of the independent factors significantly associated with severe fibrosis (F3-4). We established a new predictive model for fibrosis of NAFLD, using logistic regression analysis: YKL-40 based fibrosis score = −0.0545 + type IV collagen 7s * 0.3456 + YKL-40 * 0.0024. Serum YKL-40 levels of HCC patients with non-cirrhotic NAFLD were significantly higher than those without HCC. Immunofluorescence staining showed that YKL-40 was expressed by macrophages in liver tissue of NAFLD patients. In conclusion, macrophage-derived YKL-40 is a feasible biomarker of liver fibrosis in NAFLD patients.

Highlights

Noninvasive markers including both serologic and imaging methods have been evaluated for Nonalcoholic fatty liver disease (NAFLD) patients to estimate steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis
Regarding the correlation among such factors, YKL-40 levels were positively correlated with type IV collagen 7s, hyaluronic acid, FIB-4 index, and WFA+ -M2BP, while they were inversely correlated with ALT and platelet count (Fig. 2a–f)
The present study showed that serum YKL-40 levels are increased in NAFLD patients with fibrosis

Summary

Introduction

Noninvasive markers including both serologic and imaging methods have been evaluated for NAFLD patients to estimate steatosis, NASH, and fibrosis. The serum YKL-40 level has been evaluated as a noninvasive marker of various chronic inflammatory and fibrotic liver diseases, including chronic hepatitis C (CHC)[15] chronic hepatitis B (CHB)[16] and alcoholic liver disease[17]. YKL-40 is believed to act as a chemoattractant for endothelial cells, can modulate angiogenesis during tissue repair and is expressed in multiple tissues including human liver[18,19,20]. We evaluated the feasibility of YKL-40 as a diagnostic marker of fibrosis in patients with NAFLD. We identified the cells capable of expressing YKL-40 in the liver of NAFLD

Objectives

Methods

Results

Conclusion