Predicting and managing liver fibrosis in biliary atresia

Regardless of the underlying etiology and success of PE, progressive liver fibrosis and eventually cirrhosis represent the dominant pathology and the end-stage of BA. Ascending bile duct injury-induced cholestasis, inflammation and ductular reaction provide profibrogenic cytokine environment leading to myofibroblast activation and rapid progression of fibrosis especially after unsuccessful portoenterostomy. Although liver fibrosis and development of cirrhosis play a crucial role in determining BA outcomes, the exact prognostic significance and dynamics of mild to moderate liver fibrosis remain unclear. Manual scoring systems categorizing the degree of liver fibrosis are prone to intra- and interobserver variability, whereas novel combinations of digital pathology with artificial intelligence quantification can provide accurate information on fibrosis structure and dynamics at the level of individual collagen fibers. Although several studies have analyzed noninvasive assessment of fibrosis at time of PE, including imaging-based elastography and different serum biomarkers, current knowledge on their accuracy during the postoperative follow-up of BA is scarce. While therapeutic management of liver fibrosis in BA remains in its infancy, the resolution potential for liver fibrosis has been demonstrated after successful PE. Achievement of effective antifibrotic treatment may require combination of different therapies with complementary modes of action like anti-inflammatory medication, antioxidants and bile acid lowering agents.