BA is characterized by early destruction of the bile ducts, leading to cholestasis, inflammation, and rapid fibrosis shortly after birth. Kasai portoenterostomy can re-establish bile flow in many infants and delay liver transplantation, yet some patients still develop progressive post-surgical liver fibrosis over time. Traditional assessment methods rely on liver biopsy, which is invasive and prone to sampling variability, while existing non-invasive markers lack sufficient accuracy. Moreover, the biological drivers of fibrosis after successful surgery appear to differ from those present at disease onset. Therefore, there is a critical need to better understand the mechanisms of post-surgical liver fibrosis and to develop a reliable tool for long-term disease monitoring and intervention.
Researchers from the University of Helsinki report new insights into long-term liver injury after Kasai portoenterostomy for BA in a review published (DOI: 10.1136/wjps-2025-001098) on December 30, 2025, in 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 findings clarify why surgery alone is insufficient to prevent chronic liver damage and highlight emerging targets for improved follow-up and treatment strategies.
The review shows that post-surgical liver fibrosis follows highly variable trajectories. While more than a half of patients eventually develop cirrhosis, a substantial subset demonstrates stable or even regressing fibrosis, particularly when bile flow is efficiently and durably restored. Molecular profiling reveals that although inflammation decreases after surgery, gene signatures associated with fibrogenesis and extracellular matrix production persist. Central to this process is ductular reaction—an abnormal expansion of bile duct–like cells and transdifferentiating hepatocytes—which strongly correlates with fibrosis severity and native liver survival.
Advanced imaging and AI–assisted histological analyses indicate these ductular cells actively participate in matrix remodeling rather than representing a passive repair response. Elevated serum bile acids emerge as key predictors of fibrosis progression, portal hypertension, and long-term outcomes, potentially by stimulating ductular reaction and myofibroblast activation. The review also evaluates non-invasive fibrosis markers, including elastography and serum biomarkers, noting their usefulness in detecting advanced disease but limited sensitivity for early fibrosis stages. Together, these findings depict BA as a chronic, evolving liver disorder in which surgery alters—but does not eliminate—the biological drivers of fibrotic injury.
According to the authors, understanding fibrosis progression after surgery requires shifting focus from short-term bilirubin normalization to long-term tissue-level changes. They emphasize that persistent ductular reaction and bile acid dysregulation represents active disease processes rather than residual damage. Recognizing these mechanisms may explain why patients with similar surgical outcomes experience markedly different disease courses. The authors stress that improved risk stratification, informed by molecular and histological markers, is essential for identifying patients who may benefit most from emerging antifibrotic or bile acid–modulating therapies.
These insights have important clinical implications for the BA management. Reliable non-invasive biomarkers could reduce reliance on repeated biopsies and enable earlier detection of high-risk patients. Targeting bile acid signaling pathways or ductular reaction may offer new therapeutic avenues to slow fibrosis progression and prolong native liver survival. More broadly, the review underscores the need for long-term, mechanism-based follow-up strategies rather than viewing surgical success as a definitive endpoint. Such an approach could improve patient outcomes, optimize timing for transplantation, and guide future clinical trials aimed at modifying disease progression rather than simply managing its consequences.
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References
DOI
10.1136/wjps-2025-001098
Original Source URL
https://doi.org/10.1136/wjps-2025-001098
About World Journal of Pediatric Surgery (WJPS)
World Journal of Pediatric Surgery (WJPS), founded in 2018, is the open-access, peer-reviewed journal in pediatric surgery area. Sponsored by Zhejiang University and Children’s Hospital Zhejiang University School of Medicine, and published by BMJ Group. WJPS aims to be a leading international platform for advances in pediatric surgical research and practice. Indexed in PubMed, ESCI, Scopus, CAS, DOAJ, and CSCD, WJPS achieved the latest Impact Factor (IF) of 1.3/Q3 and an estimate 2025 IF of 2.0.