Abstract

It has been suggested that mercaptans are important factors in the pathogenesis of hepatic encephalopathy. Using a gas liquid chromatographic technique which uses propanethiol as internal standard and a sulphur specific detector, blood methanethiol concentration was found to be significantly risen in encephalopathic patients with liver disease (13.2 +/- 1.0 nmol/ml; n = 47) compared with control subjects (5.7 +/- 0.3, n = 29; p less than 0.05) and non-encephalopathic patients with liver disease (7.7 +/- 1.1, n = 35; p less than 0.05) but ethanethiol and dimethylsulphide concentrations were similar in the three groups. Blood methanethiol, however, was not clearly related to coma grade, similar values being found in deeply comatosed patients to those showing only mild cerebral dysfunction. When rats were injected with 40-120 mumol methanethiol a range of responses was obtained which varied between normal consciousness and coma. The minimum blood concentration of methanethiol associated with coma (200 nmol/ml) was at least 10-fold greater than in patients with hepatic encephalopathy but brain concentrations were similar in comatose rats and those which remained awake. Blood methanethiol concentrations were similar in control and germ free rats and did not rise in cirrhotics or controls after ingestion of 2 g methionine. It is concluded that while methanethiol may accumulate in hepatic coma, it is unlikely to be of major pathogenetic importance. Endogenous mercaptans are unlikely to originate from bacterial metabolism in the gut.