Previous studies suggest reduced hepatic endothelial nitric oxide synthase activity contributes to increased intrahepatic resistance.
Asymmetric dimethylarginine is an endogenous nitric oxide synthase inhibitor.
It undergoes hepatic metabolism via dimethylarginine-dimethylamino-hydrolase, and is derived by the action of protein-arginine-methyltransferases.
Dr Rajiv Jalan and colleagues from England assessed whether asymmetric dimethylarginine, and its stereo-isomer symmetric dimethylarginine, are increased in alcoholic hepatitis patients.
The team of doctors determined any relationship with severity of portal hypertension and outcome.
|Dimethylarginine scores were better outcome predictors than Pugh score|
The doctors studied 52 patients with decompensated alcoholic cirrhosis.
Of these patients, 27 had acute alcoholic hepatitis and cirrhosis, in whom hepatic venous pressure gradient was higher than cirrhosis alone.
The hepatic venous pressure gradient correlated with asymmetric dimethylarginine measurement.
The doctors found that both plasma asymmetric- and symmetric -dimethylarginine were higher in alcoholic hepatitis patients, and in nonsurvivors.
Dimethylarginine-dimethylamino-hydrolase protein expression was reduced and protein-arginine-methyltransferase-1 increased in alcoholic hepatitis livers.
The team termed the combined sum of asymmetric dimethylarginine and symmetric dimethylarginine a dimethylarginine score.
The doctors observed that the dimethylarginine scores were better predictors of outcome compared with Pugh score.
In addition, the team noted that this score was a better predictor of outcome than Model End-Stage Liver Disease score, and Maddrey's discriminant-function.
Dr Jalan's team concludes, “Alcoholic hepatitis patients have higher portal pressures associated with increased asymmetric dimethylarginine.”
“This may result from decreased breakdown or decreased hepatic dimethylarginine-dimethylamino-hydrolase, and/or increased production.”
“Elevated dimethylarginines may serve as important biological markers of deleterious outcome in alcoholic hepatitis.”