Abnormal methylation capacity in human liver cirrhosis.

To investigate the influence of liver cirrhosis on the capacity of methylation, the urinary excretion of the methylated forms of arsenic was measured by atomic absorption spectrometry after the administration of a small dose of inorganic arsenic. The study was carried out in 13 normal controls, 18 patients with various clinical conditions, but without evidence of parenchymal liver disease, and 38 with cirrhosis of varied aetiology and severity. In normal controls, the percentage of arsenic excreted as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) averaged 12.3 +/- 2.8% and 23.3 +/- 6.4%, respectively, and was not significantly different from that obtained in disease controls. The presence of liver cirrhosis did not affect the percentage of the injected dose excreted within 24 h. However, cirrhotic patients excreted significantly less MMA (4.7 +/- 3.3, p less than 0.001) and more DMA (40.4 +/- 16.6%, p less than 0.001). The amount of MMA correlated with the 14C aminopyrine breath test (r = 0.43) and was invariably lower than the normal range in patients with severe liver disease. These findings indicate that liver cirrhosis is associated with profound abnormalities of the methylation pathway, which might have potential consequences in the metabolism of endogenous amines and xenobiotics.