Markedly elevated levels of plasma advanced glycation end products in patients with liver cirrhosis - amelioration by liver transplantation

Abstract

Background/aims: Modification by advanced glycation renders macromolecules susceptible to elimination in the liver via scavenger receptors. Thus, in advanced liver disease an accumulation of advanced glycation end products (AGEs) in circulation might occur, due to the reduction of effective liver mass.

Methods: Plasma AGE levels (fluorescent AGEs-AGE-Fl and N(epsilon)-carboxymethyllysine - CML) were determined in 51 patients with liver cirrhosis (Ci) and 19 healthy controls. Five patients were followed 36 months after liver transplantation.

Results: In cirrhotic patients, markedly elevated concentrations of AGEs were revealed (AGE-Fl: control, 0.3+/-0.01 x 10(5) AU, Ci: 1.06+/-0.06 x 10(5) AU, P<0.01; CML, control: 431.7+/-16.3 ng/ml, Ci: 647.6+/-258.5, P<0.01). CML levels correlated with the severity of liver disease, as determined by clinical score (r=0.663, P<0.001), albumin level (r=0.704, P<0.001) and monoethylglycinexylide test (r=0.852, P<0.01). Reduced renal function contributed to the rise of CML in proportion to the degree of renal impairment. Liver transplantation resulted in about 50% decline of CML levels within 3 months, while impairment of renal function still persisted, underlying the central role of the liver for AGE removal.

Conclusions: In liver Ci, hepatic removal of AGEs is impaired. With regard to the toxicity of AGEs, their accumulation could be of pathophysiological relevance.