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  • Title: Very low bilirubin after portoenterostomy improves survival of the native liver in patients with biliary atresia by deferring liver fibrogenesis.
    Author: Hukkinen M, Kerola A, Lohi J, Jahnukainen T, Heikkilä P, Pakarinen MP.
    Journal: Surgery; 2019 Apr; 165(4):843-850. PubMed ID: 30514566.
    Abstract:
    BACKGROUND: Progression of fibrosis and ensuing complications determine the postoperative course of patients operated on for biliary atresia. We evaluated predictors of the progression of fibrosis in the native liver after operative treatment. METHODS: Among patients whose bilirubin decreased to <34 µmol/L after portoenterostomy (n = 41), predictors of follow-up cirrhosis and the progression of fibrosis were analyzed with logistic regression and survival of their native liver was evaluated with the Kaplan-Meier method. Areas under receiving operating characteristic were used to define optimal cutoffs. RESULTS: After median follow-up of 5.2 years (interquartile range 1.6-10.2) after portoenterostomy, liver biopsies showed cirrhosis in 53% of patients, and the Metavir stage remained stable or decreased in 38%. The development of cirrhosis was predicted by total or conjugated bilirubin ≥170/120 µmol/L at the time of portoenterostomy (P ≤ .009); normalization of bilirubin within 1.9 months (P = .002); total or conjugated bilirubin ≥ 12.5/7.5 µmol/L (P = .002) and aspartate aminotransferase-to-platelet ratio ≥ 0.55 at 3 months postoperatively (P = .001); and total or conjugated bilirubin ≥ 7.5/2.5 µmol/L (P ≤ .001), aspartate aminotransferase-to-platelet ratio ≥ 0.63 (P = .004), and gamma glutamyl transferase ≥ 266 U/L (P = .007) at 6 months postoperatively. In multiple regression analysis, conjugated bilirubin ≥ 2.5 µmol/L at 6 months increased the risk of cirrhosis 35-fold (P = .020), and other predictors were not predictive. Total or conjugated bilirubin < 12.5/7.5 µmol/L (P ≤ .014), aspartate aminotransferase-to-platelet ratio < 0.55 at 3 months (P = .006), and total or conjugated bilirubin < 7.5/2.5 µmol/L at 6 months postoperatively (P ≤ .014) were the strongest predictors of a stable, nonprogressive fibrosis. Decreases in total or conjugated bilirubin to < 12.5/7.5 µmol/L by 3 months and to < 7.5/2.5 µmol/L by 6 months improved survival of the native liver (log-rank P ≤ .025). Age at follow-up or at portoenterostomy, anatomic type of biliary atresia, use of postoperative steroids, and episodes of cholangitis were unrelated to the progression of fibrosis or the development of cirrhosis (P = not significant). CONCLUSION: Among patients whose serum bilirubin normalizes after portoenterostomy, its rapid decrease to very low levels prolongs the survival of their native liver by delaying the progression of fibrosis.
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