Soluble CD163 and mannose receptor as markers of liver disease severity and prognosis in patients with primary biliary cholangitis

Introduction: In primary biliary cholangitis (PBC), macrophages are involved in liver inflammation and fibrosis. The macrophage activation markers, soluble (s)CD163 and mannose receptor (sMR) are associated with liver disease severity and prognosis in other chronic liver diseases. We aimed to investigate sCD163 and sMR in patients with PBC. Methods: We investigated PBC patients from the Italian PBC Study Group cohort and measured macrophage activation markers in serum at study enrolment. Patients were followed from enrolment until they experienced an event or were censored at their last visit. Events were defined as follows: (a) death from a liver-related cause; or (b) liver transplantation (LT) for PBC. We used Cox regression to investigate the associa- tion between sCD163 and sMR and long-term prognosis. Results: In total, 202 PBC patients were included. Median age was 62 years (inter- quartile range (IQR), 53-71) at enrolment and 93% were women. Median sCD163 was 3.43 mg/L (IQR 2.48-5.35) and median sMR was 0.35 mg/L (IQR 0.28-0.45). There was an increase in sCD163 and sMR with increasing alkaline phosphatase. Two hundred and one patients were followed for a median of 8.6 years, and sCD163 and sMR pre- dicted long-term risk of liver-related death or LT in univariate analyses, while sCD163 was also associated with outcome after confounder adjusting (adjusted HR = 1.14, 95% CI 1.00-1.30). Finally, we showed an increase in the prediction accuracy of poor outcome by adding sCD163 to the UK-PBC risk score. Conclusion: The macrophage activation markers sCD163 and sMR represent a non- invasive measure of PBC disease severity that provides useful long-term prognostic information.