Very low bilirubin after portoenterostomy improves survival of the native liver in patients with biliary atresia by deferring liver fibrogenesis

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.

Regulation of bile acid metabolism in biliary atresia: reduction of FGF19 by Kasai portoenterostomy and possible relation to early outcome

“…LCA and DCA are not presented in Table , as both free and conjugated LCA and DCA were below detection limit in the majority of the samples at both time‐points. The median level of conjugated bilirubin, which is routinely used to monitor disease progression in biliary atresia after KPE , had decreased from 169 μmol L −1 at KPE to 50 μmol L −1 at follow‐up, Fig. e.…”

Peri-Operative Liver Fibrosis and Native Liver Survival in Pediatric Patients with Biliary Atresia: A Systematic Review and Meta-Analysis

“…Characteristics of the 28 studies with 1,171 pediatric patients who had BA and underwent Kasai operation are located in Table 1 . Briefly, there were 25 cohort [ 26 27 28 29 30 31 32 33 34 36 37 39 40 41 45 46 47 48 49 50 51 52 53 54 55 ] and 3 case control studies [ 35 56 57 ]. Six hundred and thirty-one patients survived with their native liver, while 573 required Ltx and 99 reportedly died after Kasai during follow-up.…”

“…Apart from 11 studies that were based on a selected group of users limited to a small sample size, patients were identified via electronic health records or referred to as a consecutive sample later subdivided into ideal vs. non-ideal outcomes [ 28 29 32 35 36 37 39 40 51 54 57 ]. Fourteen studies described pathologists being independently blinded to NLSR status [ 29 31 32 33 34 35 36 39 40 48 49 51 54 57 ]. Length of follow-up was 12 months for capturing survival outcomes in 17 studies [ 26 27 28 29 31 34 35 36 37 46 47 48 50 51 54 56 57 ].…”

“…Fourteen studies described pathologists being independently blinded to NLSR status [ 29 31 32 33 34 35 36 39 40 48 49 51 54 57 ]. Length of follow-up was 12 months for capturing survival outcomes in 17 studies [ 26 27 28 29 31 34 35 36 37 46 47 48 50 51 54 56 57 ]. The studies were mainly scored as ‘poor’ because they did not describe adjusting for confounders in a regression model, such as age at Kasai operation, anatomical pattern, polysplenia syndrome, level of centre experience, sex, albumin, total or direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and/or degree of liver failure.…”

“…Consequently, we extracted the actuarial survival rate at the designated follow-up period (2-, 5-, 10- or 20-years) [ 26 ]. For studies that did not explicitly state NLSR, we extracted data based on how the authors defined “favourable outcome” or “success of operation.” Hence, we extracted the frequency of patients with normal living function without cholangitis or portal hypertension [ 27 ], patients with good quality of life without jaundice relapsing [ 28 ], normal lab parameters and no evidence of medical chronic liver disease [ 29 ], absence of cirrhosis [ 30 31 ] or serum total bilirubin <2 mg/dL at follow-up post-Kasai operation [ 32 33 34 35 36 ].…”