Elevated serum levels of methylglyoxal are associated with an impaired liver function and liver-related complications in patients with liver cirrhosis

Background Methylglyoxal (MGO) is a highly reactive carbonyl species (RCS), and forms Advanced Glycation Endproducts (AGEs) which bind to their receptor (RAGE) leading to a severe inflammatory response. An increased systemic inflammation is a major driver of the progression from compensated to decompensated liver cirrhosis. However, the role of circulating MGO levels and its association with the severity of liver cirrhosis remains unknown.

Aims To investigate MGO serum concentrations by means of high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS), and to evaluate the impact on liver-related complications in patients with liver cirrhosis.

Methods A total of 51 patients with a diagnosis of liver cirrhosis undergoing a measurement of the hepatic venous pressure gradient (HVPG) were prospectively enrolled. Serum concentrations of MGO (ng/ml) were analysed using HPLC-MS/MS, and clinical and laboratory assessment was performed at baseline.

Results In this cohort, 51 % of patients showed a compensated (n = 26) and 49 % (n = 25) a decompensated liver cirrhosis. Patients with a liver cirrhosis Child-Pugh-Stage C showed higher MGO concentrations (p < 0.001) in comparison to Child-Pugh-Stage A and B, respectively. MGO levels were significantly higher in patients with a decompensated as compared to a compensated liver cirrhosis (p < 0.001). A strong correlation with an impaired liver function as assessed by labMELD (r = 0.53, p < 0.001), liver synthesis (albumin: r = -0.45, p = 0.001) and bilirubin (r = 0.46, p = 0.001) was seen. Furthermore, patients with ascites presented with higher levels of MGO compared to patients without ascites (p = 0.008). Moreover, MGO levels were closely linked to other inflammatory markers (IL-6: r = 0.40, p = 0.004).

Conclusion Circulating levels of MGO strongly correlate with the severity of liver cirrhosis and liver-related parameters and complications. MGO represents an important mediator of systemic inflammation during the progression of liver cirrhosis and may be a potential biomarker of disease severity.

Publication History

Article published online:
07 September 2021