The results of a randomized double blind controlled trial evaluating malotilate in primary biliary cirrhosis. A European multicentre study group

Abstract

One hundred and one patients were included in a double-blind controlled trial to determine whether malotilate (diisopropyl 1,3-dithiol-2-ylidene malonate) is therapeutically effective in primary biliary cirrhosis. Fifty-two patients received malotilate (500 mg three times a day) and 49 patients placebo. The mean follow-up time was 28 months (range 6-46 months). The large majority of patients did not have advanced liver disease since only ten patients were in Child-Pugh class B and none in class C, and the median bilirubin and albumin at entry were normal. Malotilate had no clear effect on pruritus. In malotilate recipients the following statistically significant biochemical changes occurred: alkaline phosphatase decreased 21%, AST 20%, ALT 40%, IgA 12% and IgM 26%. In the placebo group no significant changes occurred. Evaluation of entry and 2-year liver biopsies indicated that malotilate diminished plasma cell and lymphocytic infiltrate and piece-meal necrosis, but had no effect on liver fibrosis. There was no difference in survival or in disease progression according to Child-Pugh criteria. In six patients receiving malotilate, but in none on placebo, treatment was discontinued due to suspected side effects. All patients recovered completely. We conclude that malotilate has an immune-modulating, anti-inflammatory but not anti-fibrotic effect in primary biliary cirrhosis. The clinical relevance of the observed benefits, however, appears too slight to recommend malotilate as single drug therapy in primary biliary cirrhosis.