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

Abstract

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.

Keywords: Biochemical response; Cytokeratin-18; Nakanuma staging system; Primary biliary cholangitis; Scheuer staging system.