To assess whether hepatic peptidyl prolyl hydroxylase (PPH) activity could serve as a practical quantitative indicator of hepatic fibrosis or aid in the categorization, diagnosis or prognosis of hepatobiliary disorders in infancy and childhood, the activity of this enzyme has been determined prospectively by a tritium release method in 97 biopsies from 94 infants and children with the following conditions: acute hepatitis of infancy, 10 patients; extrahepatic biliary atresia, 13; previous hepatitis of infancy, 8; α-1-antitrypsin deficiency, 6; chronic active hepatitis, 17; chronic persistent hepatitis, 5; glycogen storage disease, 5; and 25 patients with a miscellanea of other liver disorders. PPH activity was considered in relation to diagnosis, biochemical and histological abnormality and subsequent prognosis over a 4-year period. Five liver biopsies which showed no histological abnormality were considered as “controls” having PPH values of 0.72 ± 0.47 (mean ± S.D.). PPH activity was significantly elevated in acute hepatitis of infancy, 9 of the 10 infants having PPH >1.66 units (i.e., mean ± 2 S.D. of the “control” value). Nine infants (70%) with extrahepatic biliary atresia also had PPH activity above this value, as did two with a-1-antitrypsin deficiency and 12 patients all in different diagnostic categories. PPH activity did not correlate with hepatic fibrosis as indicated by hepatic hydroxyproline concentration or by histological assessment, or with biochemical tests of liver function within any diagnostic group or in the series as a whole.
PPH activity was similar in biopsies with and without histological features of cirrhosis. Of the 32 patients with significantly elevated PPH activity, deterioration of their hepatic state in the subsequent 4 years occurred in only 10: 5 with extrahepatic biliary atresia and individual children with acute hepatitis of infancy, α-1-antitrypsin deficiency, biliary hypoplasia, cystic fibrosis and biliary cirrhosis associated with hypogammaglobulinemia.
Thus, although elevated PPH activity may indicate an increase in hepatic collagen biosynthesis at the time of biopsy, it does not appear to be a prognostic indicator of progressive liver damage. We conclude that the determination of hepatic PPH activity is of no diagnostic or prognostic value in hepatobiliary disorders in childhood, and the need for a practical method of monitoring persisting or continuing accumulation of fibrous tissue within the liver remains.