FIG. 4.

Clinical outcomes. (A) Four of five cases of kernicterus (blue solid line) occurred within the first 6 weeks of age. Two (7%) patients died (purple dashed line): 1 from respiratory complications of neurological injury and the other from a cause unrelated to CN1 or its treatment. The youngest patient to receive a liver transplant (green dashed line) was 4.7 years old, and median age at transplant was 16.2 years. Perpendicular hatches indicate age at census. Note different scales (months and years) of the divided abscissa. (B) In all 17 transplanted patients, serum bilirubin concentration decreased within a few postoperative days and remained normal thereafter (shown for three representative cases, with timing of liver transplantation indicated by corresponding arrowhead along the upper frame). (C) Most explants showed canalicular bile plugs (black arrows), a sign of intrahepatic cholestasis. (D) Nine (60%) livers had evidence of fibrosis ranging from mild to severe, seen here as central–central bridging on Masson trichrome stain. (E) The weighted liver fibrosis score (L_f) correlated with serum bilirubin averaged over the patient’s lifetime (r = 0.60, P < 0.0023), calculated from a mean of 32 serum bilirubin levels per patient. (F) Based on data from all 28 UGT1A1 c.222C>A homozygotes (416 paired values), there was a modest but statistically significant correlation (r = 0.24; P < 0.0001) between simultaneously measured unconjugated bilirubin and alanine transaminase (ALT; log10 scale). Gray shading represents the normal reference range for ALT.