Are stable postoperative biliary atresia patients really stable?

Abstract

Transforming growth factor-beta 1 (TGF beta-1) is an important mediator of liver-cell proliferation and replication that is implicated in hepatic fibrosis (HF). Hepatic stellate cells (HSC) are activated by TGF beta-1 and are the main precursor cells involved in fibrogenesis. The correlation between serum TGF beta-1, activated HSC in liver-biopsy specimens, and liver biochemistry was investigated to determine the value of TGF beta-1 as an indicator of clinical status in postoperative biliary atresia (BA) patients. Thirty-two postoperative BA patients (mean age 11.2 +/- 2.8 years) and 13 normal controls (mean age 10.3 +/- 3.7 years) were studied. Based on average liver function test (LFT) results over a 3-month period immediately prior to this study, the BA patients were divided into group I (anicteric, normal LFT; n = 10); group II (anicteric, elevated liver transaminases; n = 12), and group III (jaundiced end-stage liver fibrosis awaiting liver transplantation; n = 10). Serum TGF beta-1 was determined using ELISA. Liver-biopsy specimens were examined with antibody against TGF beta-1 and alpha-smooth muscle actin (SMA) antibody for detection of activated HSC. Serum TGF beta-1 was significantly higher in groups I (11.4 +/- 3.7 ng/ml; P < 0.01) and II (23.3 +/- 11.3 ng/ml; P < 0.001) than in group III (3.0 +/- 1.5 ng/ml) and controls (4.5 +/- 2.5 ng/ml) despite normal LFT in group I. The 3 subjects with the highest serum TGF beta-1 in group II had bile lakes. Biopsies from groups I and II were strongly positive for TGF beta-1 in hepatocytes and Kupffer cells and for activated HSC detected by SMA compared with group III and controls. Because serum TGF beta-1 and activated HSC are only present during active fibrosis, we conclude that there is progressive fibrogenesis even in seemingly normal postoperative BA patients. In particular, bile lakes should be regarded as a key sign of progressive HF, the presence of which should be regarded with extreme caution. We suggest that serum TGF beta-1 could be used as an accurate indicator of progressive fibrogenesis in postoperative BA patients.