Tryptophan catabolites as prognostic and diagnostic biomarkers for the severity of chronic liver diseases

Hani Oweira, Imad Lahdo, Arianeb Mehrabi. Department of Visceral Surgery, University of Heidelberg, Germany.

Background: The initial step in the kynurenine pathway is oxidation of tryptophan (Trp) to N-formylkynurenine and is catalyzed by one of two heme enzymes, tryptophan -2,3-dioxygenase (TDO) expressed mainly in liver , and indoleamine 2,3-dioxygenase (IDO), which expressed in many tissues and cell types. The role of tryptophan metabolites in chronic liver disease had not been widely studied. The aim of the present study is to investigate the correlation between tryptophan metabolites [Kynurenine (Kyn), Kynurenic acid (Kyna), Quinolinic acid (Qun)] and MELD score [Group-I=MELD 1-10; Group-II=MELD 11-18; and Group-III=MELD 19-40] in order to find prognostic and diagnostic biomarkers for the severity of chronic liver failure.

Method: Ninety-Eight potential cirrhotic liver patients who were categorized in 3 groups according to MELD (Model of End Stage Liver Disease) formula (age 53.1 ± 10.5 years; 71 male; Group-I: n= 22; Group-II: n= 34; and Group-III: n= 42) were included in the study. Trp and its metabolites Kyn, Kyna, Qun were measured by using tandem mass spectrometry. Kyn/Trp ratio was calculated to estimate IDO/TDO activity. Kruskal-Wallis test was used for statistical evaluation.

Result: Serum levels of Kyn, Kyna and Qun, as well as Kyn/Trp ratios, however, were positively correlated with disease severity (Kruskal-Wallis test: p<0.0001 for all investigations). The inflammatory marker C-reactive protein (CRP) was significantly increased according to liver disease severity (Kruskal-Wallis test: p<0.0001). There were positive correlations between serum Kyn, Kyna, Qun, Kyn/Trp ratios and CRP (p<0.0001 for all investigations).

Conclusion: Our results indicate that measurement of Kyn pathway metabolites and IDO/TDO activity are useful markers of chronic inflammation and disease severity in patients with end stage liver diseases.