New findings on long-term liver injury after Kasai portoenterostomy for biliary atresia

New findings on long-term liver injury after Kasai portoenterostomy for biliary atresia

BA is characterized by early destruction of the bile ducts, leading to cholestasis, inflammation, and rapid fibrosis shortly after birth. Kasai portoenterostomy can restore bile flow in many infants and delay liver transplantation. However, some patients still develop progressive postoperative liver fibrosis over time. Traditional assessment methods are based on liver biopsy, which is invasive and prone to sample variability, while existing non-invasive markers are not sufficiently accurate. Furthermore, the biological drivers of fibrosis following successful surgery appear to be different from those present at the onset of the disease. Therefore, there is an urgent need to better understand the mechanisms of postoperative liver fibrosis and to develop a reliable tool for long-term disease monitoring and intervention.

Researchers at the University of Helsinki report new findings on long-term liver damage after Kasai portoenterostomy for BA in a review published on December 30, 2025 (DOI: 10.1136/wjps-2025-001098).World Journal of Pediatric Surgery. The review examines how liver fibrosis progresses after initially successful surgery, evaluates current methods for fibrosis assessment, and links molecular and histological changes to long-term clinical outcomes. These results illustrate why surgery alone is not enough to prevent chronic liver damage and provide new targets for improved follow-up and treatment strategies.

The review shows that postoperative liver fibrosis has very different courses. While more than half of patients eventually develop liver cirrhosis, a significant proportion of patients demonstrate stable or even regressive fibrosis, particularly when bile flow is restored efficiently and permanently. Molecular profiling analyzes show that although inflammation decreases after surgery, gene signatures associated with fibrogenesis and extracellular matrix production remain. Central to this process is the ductular response—an abnormal expansion of bile duct-like cells and transdifferentiating hepatocytes—which correlates strongly with the severity of fibrosis and survival of the native liver.

Advanced imaging and AI-assisted histological analyzes suggest that these ductular cells are actively involved in matrix remodeling and do not represent a passive repair response. Elevated serum bile acids emerge as important predictors of fibrosis progression, portal hypertension and long-term sequelae, possibly through stimulation of ductular response and myofibroblast activation. The review also evaluates non-invasive fibrosis markers, including elastography and serum biomarkers, and notes their usefulness in detecting advanced disease, but notes limited sensitivity for early stages of fibrosis. Taken together, these results portray BA as a chronic, evolving liver disease in which surgery alters – but does not eliminate – the biological drivers of fibrotic damage.

According to the authors, to understand the progression of fibrosis after surgery, the focus must shift from short-term bilirubin normalization to long-term changes at the tissue level. They emphasize that persistent ductular reactions and bile acid dysregulation represent active disease processes and not residual damage. Recognition of these mechanisms may explain why patients with similar surgical outcomes experience significantly different disease courses. The authors emphasize that improved risk stratification based on molecular and histological markers is essential for identifying patients who may benefit most from new antifibrotic or bile acid modulating therapies.

These findings have important clinical implications for BA management. Reliable non-invasive biomarkers could reduce the reliance on repeat biopsies and enable earlier detection of high-risk patients. Targeting bile acid signaling pathways or ductular responses could provide new therapeutic opportunities to slow fibrosis progression and prolong native liver survival. More broadly, the review highlights the need for long-term, mechanism-based follow-up strategies rather than considering surgical success as the final endpoint. Such an approach could improve patient outcomes, optimize the timing of transplantation, and guide future clinical trials aimed at altering disease progression rather than simply managing its consequences.

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