Medical Molecular Morphology

, Volume 51, Issue 3, pp 176–185 | Cite as

Serum levels of a cell death biomarker predict the development of cirrhosis-related conditions in primary biliary cholangitis

  • Manabu HayashiEmail author
  • Kazumichi Abe
  • Masashi Fujita
  • Ken Okai
  • Atsushi Takahashi
  • Yoshihiro Nozawa
  • Hiromasa Ohira
Original Paper


Non-invasive predictors for the development of cirrhosis-related conditions are needed for patients with primary biliary cholangitis (PBC). We investigated the association between cytokeratin-18 fragments (M30 and M65) and liver histology, treatment response and the development of cirrhosis-related conditions in patients with PBC. We retrospectively reviewed the clinical data of 111 individuals with biopsy-proven PBC. Serum M30 and M65 levels were measured using stored sera. M30 were significantly decreased after treatment, but there was no significant change in the M65 levels. M65 was significantly higher in non-responders according to the Paris-I and Paris-II definitions. In the multivariate analysis, high levels of M65 were significantly associated with advanced Scheuer stage (odds ratio 5.86; 95% confidence interval 0.55–22.2; P = 0.009) and with the development of cirrhosis-related conditions (hazard ratio 3.94; 95% confidence interval: 1.06–14.5, P = 0.039). Among PBC patients without cirrhosis, those with high serum M65 levels at baseline were at higher risk of developing cirrhosis-related conditions (log-rank test; P = 0.001). High levels of serum M65 may be a non-invasive and early predictor of the development of cirrhosis-related conditions in PBC patients. Our findings may help initiate therapies earlier for those at risk for cirrhosis.


Primary biliary cholangitis Cytokeratin-18 Biochemical response Nakanuma staging system Scheuer staging system 



We thank C. Sato and R. Hikichi for their excellent technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2018

Authors and Affiliations

  1. 1.Department of GastroenterologyFukushima Medical University School of MedicineFukushimaJapan
  2. 2.Department of PathologyShirakawa Kousei General HospitalShirakawaJapan

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