REVERSAL OF INDIAN CHILDHOOD CIRRHOSIS BY D-PENICILLAMINE THERAPY

Serial liver biopsy changes have been reviewed in 30 patients with Ind ian childhood cirrhosis (ICC) who were randomly allocated to receive t reatment with penicillamine in a dose of 20 mg/kg/day, 10 of whom also received prednisolone, and five receiving placebo. The latter died wi thin 185 (mean, 149) days of starting treatment. Nine receiving penici llamine died within 540 (mean, 338) days, but the remainder are well 5 .1-9.3 years after commencing treatment. Initial biopsies showed sever e hepatocellular injury, pericellular fibrosis, inflammatory infiltrat ion, and orcein-staining granules. Second biopsies taken within 6 mont hs of starting penicillamine usually showed persistence of inflammatio n and an increase in nodularity with thick and thin active septae. Sub sequently the appearances were of an inactive micronodular cirrhosis, with reduction in septal inflammatory infiltrate, hepatocellular injur y, and intensity of orcein staining. This further improved to a stage of incomplete fibrous septae. The last liver biopsies at 6-60 months ( in 21 survivors) showed almost normal histology in four, incomplete fi brous septae in five, and inactive micronodular cirrhosis with thin se ptae in 12. Mean liver copper concentrations decreased from 1,407 (SEM , 121) mu g/g at presentation to 925 (183), 317 (100), and 127 (35) at 6, 6-18, and >18 months after starting treatment. By contrast, a seco nd biopsy taken in the 6 months after diagnosis in placebo-treated chi ldren showed persistence of ICC with increase in inflammation, fibrosi s, and orcein staining.