Changes in serum immunoreactive prolyl hydroxylase protein (IRPH), galactosylhydroxylysyl glucosyltransferase activity (GGT) and the aminoterminal propeptide of type III procollagen [Pro(III)-N-P] were studied in 21 patients with primary biliary cirrhosis during a follow-up period of up to three years. The patients received either D-penicillamine (600 mg/day), medroxyprogesterone acetate (5 mg/day), or a placebo, or no treatment after the D-penicillamine or medroxyprogesterone medication, each period lasting from nine to 15 months. The individual serum IRPH, GGT, and Pro(III)-N-P concentrations exceeded the upper normal limit in most patients. No significant changes were found in any of these three serum markers during any of the five different periods, nor was there any evidence for a decrease in the raised prolyl 4-hydroxylase activity in the hepatic biopsy specimens in response to any of the treatments. Galactosylhydroxylysyl glucosyltransferase activity decreased significantly in these specimens during medroxyprogesterone therapy, but the interpretation of this, the only positive change, remains unclear. The data suggest that D-penicillamine or medroxyprogesterone therapy may have no favourable effect on the increased hepatic collagen formation involved in primary biliary cirrhosis.
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