Quantitative measurements of M2BPGi depend on liver fibrosis and inflammation

Haruki Uojima; Kazumi Yamasaki; Masaya Sugiyama; Masayoshi Kage; Norihiro Ishii; Ken Shirabe; Hisashi Hidaka; Chika Kusano; Miyako Murakawa; Yasuhiro Asahina; Takashi Nishimura; Hiroko Iijima; Kazumasa Sakamoto; Kiyoaki Ito; Keisuke Amano; Takumi Kawaguchi; Nobuharu Tamaki; Masayuki Kurosaki; Takanori Suzuki; Kentaro Matsuura; Akinobu Taketomi; Satoru Joshita; Takeji Umemura; Sohji Nishina; Keisuke Hino; Hidenori Toyoda; Hiroshi Yatsuhashi; Masashi Mizokami

doi:10.1007/s00535-024-02100-3

Quantitative measurements of M2BPGi depend on liver fibrosis and inflammation

J Gastroenterol. 2024 Apr 16. doi: 10.1007/s00535-024-02100-3. Online ahead of print.

Authors

Haruki Uojima^{1

2}, Kazumi Yamasaki³, Masaya Sugiyama⁴, Masayoshi Kage⁵, Norihiro Ishii⁶, Ken Shirabe⁶, Hisashi Hidaka⁷, Chika Kusano⁷, Miyako Murakawa⁸, Yasuhiro Asahina^{8

9}, Takashi Nishimura¹⁰, Hiroko Iijima¹⁰, Kazumasa Sakamoto¹¹, Kiyoaki Ito¹¹, Keisuke Amano¹², Takumi Kawaguchi¹², Nobuharu Tamaki¹³, Masayuki Kurosaki¹³, Takanori Suzuki¹⁴, Kentaro Matsuura¹⁴, Akinobu Taketomi¹⁵, Satoru Joshita¹⁶, Takeji Umemura¹⁶, Sohji Nishina¹⁷, Keisuke Hino^{17

18}, Hidenori Toyoda¹⁹, Hiroshi Yatsuhashi³, Masashi Mizokami²⁰

Affiliations

¹ Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan. lb-uojima@hospk.ncgm.go.jp.
² Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. lb-uojima@hospk.ncgm.go.jp.
³ Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Ōmura, Japan.
⁴ Department of Viral Pathogenesis and Controls, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
⁵ Department of Pathology, Junshin Gakuen University, Fukuoka, Japan.
⁶ Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan.
⁷ Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
⁸ Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Yushima, Bunkyo-Ku, Tokyo, Japan.
⁹ Department of Liver Disease Control, Tokyo Medical and Dental University, Yushima, Bunkyo-Ku, Tokyo, Japan.
¹⁰ Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, Nishinomiya, Hyogo, Japan.
¹¹ Department of Gastroenterology, Aichi Medical University, Nagakute, Aichi, Japan.
¹² Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi-Machi, Kurume, Fukuoka, Japan.
¹³ Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
¹⁴ Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
¹⁵ Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
¹⁶ Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Asahi, Matsumoto, Japan.
¹⁷ Department of Hepatology and Pancreatology, Kawasaki Medical School, Aichi, Japan.
¹⁸ Digestive Disease Center, Shunan Memorial Hospital, Yamaguchi, Japan.
¹⁹ Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan.
²⁰ Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan.

PMID: 38625546
DOI: 10.1007/s00535-024-02100-3

Abstract

Background: The relationship between liver fibrosis and inflammation and Mac-2-binding protein glycosylation isomer (M2BPGi) in patients with chronic liver disease (CLD) other than hepatitis C remains uncertain, owing to the limitations of qualitative methods. Here, we evaluated the influence of liver fibrosis and inflammation on quantitative M2BPGi (M2BPGi-Qt) in CLD, considering each etiology.

Methods: We recruited 1373 patients with CLD. To evaluate the influence of liver fibrosis and inflammation on M2BPGi-Qt levels, we assessed M2BPGi-Qt levels at each fibrosis and activity stage within different etiologies of CLD based on pathological findings. Subsequently, we evaluated if the accuracy of fibrosis staging based on M2BPGi-Qt could be improved by considering the influence of liver inflammation.

Results: In patients with viral hepatitis, non-alcoholic fatty liver disease, and primary biliary cholangitis, the median M2BPGi-Qt levels increased liver fibrosis progression. Median M2BPGi-Qt levels were not associated with the degree of fibrosis in patients with autoimmune hepatitis (AIH). Median M2BPGi-Qt levels increased with the progression of liver activity in all etiologies. A significant difference was found at each stage in AIH. Considering the liver inflammation, we established an algorithm, M2BPGi-Qt, to determine the alanine aminotransferase-to-platelet ratio (MAP-R) in liver cirrhosis (LC). The area under the receiver operating characteristic curve (AUC) of MAP-R was higher than that of the M2BPGi-Qt for detecting LC (AUC MAP-R = 0.759 and M2BPGi-Qt = 0.700, p < 0.001).

Conclusions: The quantitative measurement system for M2BPGi depends on liver fibrosis and inflammation, regardless of etiology. Liver inflammation complicates the interpretation of M2BPGi-Qt results when assessing the fibrosis stage.

Keywords: Chronic liver disease; Liver fibrosis; Liver inflammation; Noninvasive marker; Quantitative measurement.