JUVENILE WILSON'S DISEASE: HISTOLOGICAL AND FUNCTIONAL CORRELATIONS DURING PENICILLAMINE THERAPY

Abstract

Clinical improvement and cupruresis occur during penicillamine(PCN) therapy for Wilson's Disease(WD), but long-term effects of the drug on hepatic morphology are virtually unknown. We studied 6 patients(pts) with WD (diagnosed at 7-24 yrs) who were clinically asymptommatic at follow-up(f/u) liver biopsy 2-7 yrs after onset of treatment. By comparison to pre-treatment biopsies (3 pts), there was marked reduction in portal fibrosis in 1 (7 yr f/u) and significant but less impressive decreases in 2 (2 yr f/u). Portal inflammation was greatly diminished in all 3, with periportal necrosis still present in 1 (2 yr f/u). None had complete restitution of normal architecture. At f/u, 3 pts on therapy for 3,5 or 7 yrs (without initial biopsy) had dense portal cirrhosis; in 2, portal lymphocytic infiltration was prominent; in 1, there was marked fatty change. Hepatocellular non-bilirubin pigment was abundant in 5/6 f/u specimens. Hepatic Cu⁺⁺ levels were 80-750 μg/g (n1<50) and did not correlate with the degree of pigment deposition or healing. Liver function reverted to normal in 5/6 pts; serum Cu⁺⁺ levels fell 50% and remained low. Hypoceruloplasminemia persisted in all. K-F rings faded or disappeared. One pt has hepatic dysfunction, cirrhosis and K-F rings despite therapy. The data show that morphological improvement occurs in some PCN-treated pts with WD, but that this is not predicted by function tests. Sequential biopsies are needed to evaluate fully the extent of healing.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD