Serum Autotaxin Levels Predict Liver-Related Events in Primary Biliary Cholangitis Patients: A Long-term Multicenter Observational Study

Abstract

Background: A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. The present study investigated whether serum autotaxin (ATX) could predict liver-related events (LRE) in PBC patients. Methods: This retrospective multicenter investigation included 190 biopsy-proven untreated PBC patients. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation to ATX levels at the time of liver biopsy Results: During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥ 1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs. 3.6%, p < 0.00001). Notably, the predictive capability of ATX for LRE in PBC patients surpassed that of FIB-4, ALBI, APRI, and M2BPGi. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, p = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, p < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32). Conclusion: Serum ATX levels may serve as a predictive marker for LRE in patients with PBC.