[Hepatotoxicity of isaxonine phosphate: 4 cases of severe subacute hepatitis]

Isaxonine phosphate is known to induce acute hepatitis which in most cases is reversible after withdrawal of the drug. The authors describe 4 new cases of hepatitis which differ from those previously reported by their evolutive and pathological features. In 3 cases, the outcome was fatal within a delay of 15-40 days despite discontinuation of the drug, and was associated with hepatic encephalopathy and ascites. In the 4 cases plasma concentration of alanine- and aspartate-aminotransferases were initially increased (up to 33 X upper normal range) and decreased to normal values in 2 cases. Plasma bilirubin levels were also elevated at first and continued to increase during the first 15 days of evolution. Pathological examination of the liver showed mild necrosis, sometimes with a piecemeal or a bridging aspect, marked fibrosis infiltrated with mononuclear and neutrophil polymorphonuclear cells and a conspicuous biliary neogenesis. In these particular cases of hepatitis due to isaxonine phosphate, occurrence in women, increased serum immunoglobulin levels, presence of autoantibodies, clinical and pathological aspects resembling those observed in iproniazid hepatitis may be suggestive of an immunological, or even autoimmune, mechanism.