Digoxin-like immunoreactive substances in chronic liver disease

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Abstract
Digoxin-like immunoreactive substances, which cross-react with digoxin antibody, have been found to have natriuretic effect and Na+,K+-ATPase inhibitory effect. The role of digoxin-like immunoreactive substances in chronic liver disease was studied by radioimmunoassay in 63 serum and 60 urine samples from 58 patients with chronic liver disease and compared with 16 controls. Although the mean serum digoxin-like immunoreactive substances level of compensated chronic liver disease patients (0.06 ± 0.05 ng per ml, p < 0.01) was higher than that of controls (0.02 ± 0.03 ng per ml), only four patients had serum digoxin-like immunoreactive substances higher than 0.10 ng per ml. Mean serum digoxin-like immunoreactive substances level was much higher in patients with decompensated chronic liver disease who had ascites (0.32 ± 0.17 ng per ml, p < 0.001), hepatorenal syndrome (0.57 ± 0.20 ng per ml, p < 0.001) and hepatic encephalopathy (0.43 ± 0.20 ng per ml, p < 0.001). Five patients with recent variceal hemorrhage requiring transfusions and saline infusion had significantly increased serum digoxin-like immunoreactive substances (mean: 0.16 ± 0.06 ng per ml, p < 0.001) before the development of clinically detectable ascites. The serum digoxin-like immunoreactive substances level was positively correlated with serum total bilirubin (r = 0.581, p < 0.001), AST (r = 0.454, p < 0.001), serum creatinine (r = 0.539, p < 0.001), urine digoxin-like immunoreactive substances (ng of urine digoxin-like immunoreactive substances per gm of urine creatinine, r = 0.578, p < 0.001) and negatively correlated with serum albumin (r=−0.604, p < 0.001), prothrombin activity (r=−0.589, p < 0.001), serum sodium (r=−0.685, p < 0.001) and urine sodium (mEq of urine sodium per gm of urine creatinine; r=−0.476, p < 0.001). The present study shows increased serum digoxin-like immunoreactive substances in decompensated chronic liver disease. The negative correlation between serum digoxin-like immunoreactive substances and urine sodium suggests that digoxin-like immunoreactive substances level is higher in patients having low urinary sodium output. This finding may be explained by a possible renal insensitivity to digoxin-like immunoreactive substances in decompensated chronic liver disease.