Blood methanethiol in alcoholic liver disease with and without hepatic encephalopathy.

Abstract

SUMMARY Blood methanethiol and ammonia concentrations were measured in 16 healthy volunteers, 52 consecutive alcoholic cirrhotics without overt hepatic encephalopathy (HE), and 42 consecutive patients with alcoholic liver disease and overt HE. The mean concentration of blood methanethiol was significantly greater than normal in the cirrhotics without overt HE, and the means of both methanethiol and ammonia were significantly greater in the patients with than in those without overt HE. Only one patient with overt HE had both normal ammonia and methanethiol blood concentrations. Twenty of the patients with HE were followed serially. The directions of change in methanethiol and ammonia were consistent with the direction of change in mental status in 85 % and 60 % respectively. All of the patients who deteriorated and died had changes in blood methanethiol that correlated with the change in mental status. We conclude that blood methanethiol is a valuable adjunct to the ammonia determination in the evaluation of the patient with possible HE. It is especially helpful in following the course of a patient with hepatic encephalopathy, both as to prognosis and as an indicator of response to therapy. Mercaptans are extremely toxic sulphur-containing compounds that appear to be largely derived from colonic bacterial metabolism of methionine. Like ammonia, mercaptans are normally efficiently removed by the liver but escape detoxification with hepatic failure or shunting of intestinal blood around the liver. Animal studies have shown that small amounts of mercaptans can cause reversible coma and can act synergistically with ammonia and fatty acids to enhance the toxicity of these substances.' In 1955, Challenger and Walshe2 established the association of mercaptans with hepatic failure by isolating methanethiol (methyl mercaptan) from the urine of a woman in deep hepatic coma, and, in 1970, Chen and his colleagues3 reported a four-fold increase in breath methanethiol in patients with hepatic failure. Recently, a method for measuring mercaptans was developed that was sufficiently sensitive to detect methanethiol in the blood of patients for the first time.4 We have applied this method to patients with hepatic failure over the past two years and are now reporting the results of this initial experience.

Breath biomarkers for detection of human liver diseases: preliminary study

“…The branched chain 2-oxyacid dehydrogenase complex probably controls the transaminative¯ux of these compounds. Degradation of methionine can also occur in the gut by the action of bacterial methionine ®-lyase (Johnston et al 1981), although it has been proposed that the gut is not the source of methanethiol and dimethyl sulphide in liver disease (McClain et al 1980). The production of methanethiol depresses the synthesis of urea (Derr and Zieve 1982), with the result that circulating levels of ammonia, biogenic amines and short-chain fatty acids are increased, thereby setting up the scenario for hepatic encephalo- Figure 6.…”

The mechanism of hepatic coma

“…With development of encephalopathy, blood methanethiol increased further. Serial changes in blood methanethiol concentration correlate well with changes in the clinical grade of encephalopathy (10).…”

Liver Disease and Protein Needs

“…Mercaptans, which are derived from bacterial metabolism of methionine, can produce coma in animals and have synergistic properties when administered with ammonia and fatty acids (188). Changes in the blood concentration of methanethiol (methyl mercap-MEZEY tan) were found to correlate with changes in the severity of encephalopathy in man (106).…”