Session Title: Category 2b. CIRRHOSIS AND ITS COMPLICATIONS: b. CLINICAL ASPECTS
THE EFFECTS OF DISEASE STAGE AND ACUTE-ON-CHRONIC LIVER FAILURE ON THE PROFILE OF PLASMA DIMETHYLARGININES IN CIRRHOSIS
S.J. Thomson1*, M.L. Cowan1, S. Musa1, R.N. Dalton2, C. Turner2, D.M. Forton1, S.J. Clark1, T.M. Rahman1
Background and aims: The role of the liver in regulating the plasma levels of asymmetric dimethylarginine (ADMA) in chronic liver disease has been the subject of increasing interest in recent years. Dimethylarginines are produced during the cellular proteolysis and methylation of nuclear proteins. ADMA plays an important role as an endogenous inhibitor of nitric oxide synthase (NOS) and is predominantly metabolised in the liver by dimethylarginine dimethylaminohydrolase (DDAH). Symmetric dimethylarginine (SDMA) has no direct effect on NOS and undergoes renal clearance. ADMA has been shown to be raised in acute liver failure and decompensated cirrhosis but no differences have been reported between controls and compensated disease in either ADMA or SDMA.
ADMA was significantly higher in cirrhosis. Notably, differences were seen between controls and early compensated disease (CPA) which further increased with disease severity (CPB/C). Higher SDMA was seen in out-patients which rose again in the in-patient population although this did not reach statistical significance.
Conclusions: The evidence of a gradation of change in ADMA throughout the spectrum of disease severity is an important finding. It has previously been considered that DDAH activity is unaffected in compensated cirrhosis but this may not be the case. In conclusion, ADMA, SDMA, and their combined interaction, are promising biomarkers in the assessment of disease severity in chronic and acute-on-chronic liver disease. The role of SDMA in renal failure and the use of the combined DMA score merits further large scale evaluation.