Serum bile acid accumulation predicts liver injury after portoenterostomy in biliary atresia

The accumulation of altered serum bile acids appears to increase the risk of liver disease progression and result in poorer transplant-free survival following Kasai portoenterostomy (KPE) for biliary atresia (BA), a study has shown.

Researchers prospectively obtained 244 serum and 105 liver specimens from 54 patients with BA after KPE. They analysed bile acids using mass spectrometry, gene expression with quantitative PCR, and histopathology through a neural network model.

After KPE, serum bile acids showed a positive association with biochemical liver injury, paediatric end-stage liver disease score, liver stiffness, histological ductular reaction, and liver fibrosis.

During follow-up, higher bile acids were observed among patients who developed portal hypertension (79.6 vs 11.9 μmol/L; p<0.0001), esophageal varices (91.6 vs 16.2 μmol/L; p<0.0001), or required liver transplantation (LT; 115.3 vs 22.0 μmol/L; p<0.0001). In time-dependent regression models, these outcomes were predicted by bile acids.

The accumulation of conjugated bile acids, cholic acid, and taurine conjugates correlated with the risk of LT and with histological liver injury. Higher serum C4 (0.04 vs 0.00 μmol/L; p=0.04) and liver CYP7A1 were seen in native liver survivors vs LT recipients (fold-change: 16.9 vs 7.0; p=0.02).

Furthermore, primary bile acids were negative associated with C4 (R, –0.38; p<0.001) and CYP7A1 (R, –0.49; p=0.01). Unlike in native liver survivors (R, –0.19; p=0.66), serum fibroblast growth factor 19 (FGF19) correlated with liver FGF19 (R, 0.59; p=0.04) without inversely correlating with serum primary bile acids in LT recipients (R, 0.26; p=0.08).

“Poor prognosis was associated with low bile acid synthesis and aberrantly increased liver FGF19,” the researchers said.