Serum Kynurenine Levels Are A Novel Biomarker To Predict The Prognosis Of Patients With Hepatocellular Carcinoma

Background We examined serum kynurenine levels in patients with chronic hepatitis C virus infection, and the relationship between serum kynurenine and prognosis in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C. Methods We retrospectively analyzed 604 patients with HCC diagnosed between January 1999 and December 2015, and 288 patients without HCC who were seen at the National Hospital Organization Nagasaki Medical Center between October 2014 and November 2017. The association between serum kynurenine and prognosis was evaluated using the Cox's proportional hazards regression analysis. Results Patients with HCC had significantly higher values of serum kynurenine than patients without HCC (median: 557.1 vs. 464.2 ng/mL, p<0.001). Five-year survival rates of HCC patients with serum kynurenine >= 900 (n = 65), 600-899 (n = 194), and <600 ng/mL (n = 345) were 30.6%, 47.4%, and 61.4%, respectively (p = 0.001, log-rank test). Multivariate analysis identified serum kynurenine as an independent predictor for prognosis of HCC patients. The hazard ratio of serum kynurenine >= 900, and 600-899 compared with serum kynurenine <600 ng/mL were 1.91 (p<0.001) and 1.37 (p = 0.015), respectively. Conclusions A high level of serum kynurenine correlated with poor prognosis of HCC. Serum kynurenine levels may be a novel biomarker to predict the prognosis of patients with HCC. The development of drugs that inhibit kynurenine production is expected to help improve the prognosis of patients with HCC.