Serum Gas6 and Axl as non‐invasive biomarkers of advanced histological stage in primary biliary cholangitis

Aim Advanced histological stage is an important factor in individual risk stratification in patients with primary biliary cholangitis (PBC). Non‐invasive biomarkers for advanced histological stage are needed. We assessed the utility of Gas6 and Axl as biomarkers for advanced histological stage in patients with PBC. Methods A total of 113 biopsy‐proven PBC patients and 20 healthy controls were included in this study. Serum Axl and Gas6 were measured using enzyme‑linked immunosorbent assay. The Gas6 / albumin ratio and Axl / albumin ratio were also evaluated as biomarkers of histological stage. Results Serum Axl (42.6 ng/mL vs. 30.6 ng/mL, P < 0.001) and Gas6 (21.1 ng/mL vs. 18.8 ng/mL, P = 0.007) levels in PBC patients were significantly higher than those in healthy controls. The Axl / albumin ratio was 10.4, and the Gas6 / albumin ratio was 7.6 in patients with PBC. Gas6 and Axl were significantly correlated with aspartate aminotransferase, bilirubin, albumin, and platelets. Gas6 and Axl levels in patients with an advanced Scheuer stage and an advanced Nakanuma stage were significantly higher than those in other patients. The area under the receiver operating characteristic curve (AUROC) of Axl, Gas6, Axl / albumin, and Gas6 / albumin for diagnosing Scheuer stage 4 was 0.733, 0.837, 0.845, and 0.893, respectively. The AUROC of Axl, Gas6, Axl / albumin, and Gas6 / albumin for diagnosing Nakanuma stage 4 was 0.794, 0.834, 0.869, and 0.898, respectively. Conclusion High levels of Gas6 and Axl were associated with advanced histological stage in PBC patients. Furthermore, the Gas6 / albumin ratio and the Axl / albumin ratio showed a high AUROC for diagnosing advanced histological stage.