Immunohistochemical study on liver fibrosis in biliary atresia

Although advanced liver fibrosis is a critical complication in influencing the outcome of biliary atresia (BA), the mechanism is poorly understood. In adult hepatic disorders, the relationships between sinusoidal liver cells (SLC) such as hepatic stellate cells (HSCs), some growth factors and enzymes concerned with extracellular matrix (ECM) metabolism have been clarified, but are unknown in BA. This study aimed to investigate such relationships in BA.

Seventeen liver samples from 14 patients with BA were immunohistochemically examined using primary antibodies such as alpha smooth muscle actin (alphaSMA), transforming growth factor beta (TGFbeta), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP)-1, MMP-2, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. The degree of liver fibrosis and these immunohistochemical findings were compared and examined semiquantitatively. Ultrathin sections from two samples were also examined with electron microscopy.

The immunoreactivity of alphaSMA and MMPs increased with the degree of liver fibrosis, whereas that of TGFbeta, PDGF, and TIMPs showed no difference in expression in groups with any degrees of fibrosis. The immunoreactivity of MMPs statistically significantly increased in fibrotic livers. Electronmicroscopically, HSCs had many filaments in their cytoplasm, showing myofibroblastic morphology.

The present study gave a different result than other reports on adult liver fibrosis. Livers with BA may be in a predominant state of fibrolysis, indicating the presence of the similar process to recovery from liver fibrosis in adults.