Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy.

Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis (PBC) METHODS: Seventy-five PBC patients who started urusodeoxycholic acid (UDCA) therapy were retrospectively enrolled. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, and BCAA-to-tyrosine ratio (BTR) were determined. The hazard ratios (HRs) of factors associated with liver-related events were analyzed by Cox proportional hazard analysis.Of the 75 patients enrolled, 12 showed a decrease in serum BCAA levels and 15 showed an increase in serum tyrosine levels. The BTR decreased in 16 patients. During a median 5.6-year follow-up, liver-related events occurred in 11 patients. Multivariate analysis revealed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48 weeks after starting UDCA therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110 μmol/L was identified as a cutoff value with an adjusted HR 20.9 (95% confidence interval: 4.3-101.5, P < 0.001). Kaplan-Meier analysis revealed that the 5-year cumulative incidences of event occurrence in patients with high and low serum tyrosine concentration were 56.5% and 5.5%, respectively (P < 0.001). The 10-year survival probabilities also showed significant differences between patients with high and low serum tyrosine concentration (44.9% vs. 92.0%, P < 0.001).Elevation of serum tyrosine concentration indicates high risk of liver-related events in PBC patients under UDCA therapy.