Analysis of the reversibility of biliary cirrhosis in young rats submitted to biliary obstruction

Abstract

Background/purpose: Biliary atresia and other liver biliary obstructions are relevant conditions in pediatric surgery due to their progression to biliary cirrhosis and indication for liver transplantation. It is known that the period during which biliary obstruction persists determines the development of cirrhosis and its reversibility after a biliary drainage procedure. However, no time or histological markers of biliary cirrhosis reversibility have been established. Materials and methods: One hundred and twenty-nine young Wistar rats underwent surgery for ligation of the common bile duct and were maintained until 8 weeks. A part of these animals was submitted to biliary drainage surgery at 2, 3, 4, 5, or 6 weeks after the initial procedure. After cyst formation at the site of obstruction, cystjejunal anastomosis was performed to restore bile flow. After biliary obstruction and drainage, liver samples were collected for histological and molecular analysis of the genes responsible for collagen deposition and fibrosis. Results: The mortality rates were 39.8% and 56.7% after the first and second procedures, respectively. Ductular proliferation (p = 0.001) and collagen deposition increased according to the period under obstruction (p = 0.0001), and both alterations were partially reduced after biliary drainage. There were no significant differences in the values of desmin and alpha-actin according to the period during which the animal remained with biliary obstruction (p = 0.09 and p = 0.3, respectively), although increased values of transforming growth factor beta 1 (TGF beta 1) occurred after 8 weeks (p = 0.000). Desmin levels decreased, and alpha-actin and TGF beta 1 levels increased according to the period under obstruction. The molecular alterations were partially reversed after biliary drainage. Conclusions: The histologic and molecular changes in the liver parenchyma promoted by biliary obstruction in the young animal can be partially reversed by a biliary drainage procedure.