Higher serum methionine levels as a predictive factor in patients with irreversible fulminant hepatic failure

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Fulminant hepatic failure (FHF) is characterized by acute massive liver necrosis in the absence of chronic liver disease, and also shows an imbalance of the amino acid levels that results from the acute necrosis of hepatocytes. In this study, we investigated the plasma free amino acid profiles in rats with FHF. Acute liver injury was induced by an intragastric administration of 4-hydroxyace-tanilide (APAP) diluted in saline in doses of 7.5 and 3.75 g of APAP per kg b.w. Animals were sacrificed at 1, 6, 12 and 24 hours after treatment. The pre-treatment amino acid profiles of plasma were typical for hepatic failure, with abnormally high levels of phenylalanine, and tyrosine and decreased levels of valine, leucine, and isoleucine. In addition, the levels of many other amino acids such as alanine, lysine, glutamine, methionine, or arginine increased. Among these increased serum amino acids levels, a significant increase of the serum methionine levels was observed in rats with FHF who died, compared to those with FHF who survived after treatments. The markedly increased serum levels of methionine may be associated with the severity of liver damage, which could lead to impaired liver regeneration and multipleorgan failure in patients with FHF.