Regression of bile duct damage and bile duct proliferation in the non-rearterialized transplanted rat liver is associated with spontaneous graft rearterialization



The aim of this study was to investigate the long-term consequences of non-rearterialization of the graft in rat liver transplantation. Liver transplantation with (AOLT) and without graft rearterialization (NOLT) was performed in anesthetized male Lewis rats. Quantitative morphometry and semiquantitative histopathology of the liver were performed at various times after operation. Volume fractions of tissue components were determined. The number of arteries and bile ducts per portal tract were measured in histological sections from both groups. Hepatic blood flow was measured using the radioactive microsphere technique in rats after NOLT (6 months). AOLT livers had a preserved lobular architecture at all time points and unaltered volume fractions. In addition, AOLT livers maintained approximately one artery and one bile duct per portal tract after transplantation. NOLT livers showed bile duct damage at 3 days, cellular infiltration and ductular proliferation at 1 week, increased ductular proliferation at 4 weeks, and fibrosis at 6 months. The volume fractions for nonhepatocyte parenchyma (3 days, 19.14 ± 1.29; 1 week, 20.44 ± 1.76; 4 weeks, 15.46 ± 3.14), bile ducts/ductules (1 week, 4.88 ± 1.07; 4 weeks, 7.20 ± 2.42), and connective tissue (4 weeks, 4.02 ± 1.66; 6 months, 14.94 ± 0.63) were significantly increased. Hepatocyte volume fraction was significantly decreased at all time points. A total of 1.58 ± 0.08 arteries/portal tract were found in NOLT livers after 4 weeks, rising to 2.44 ± 0.10 arteries/portal tract after 6 months. At 6 months, hepatic arterial blood flow (0.69 mL/min/g) was significantly higher (P < 0.02) than control (0.25 mL/min/g). The findings indicate that NOLT leads to a time-dependent overall derangement of liver structure, possibly due to bile duct damage induced by lack of an arterial blood supply. Spontaneous graft rearterialization may be responsible for the regression of bile duct damage and proliferation noted at the later stages. Nevertheless, biliary fibrosis may be a long-term consequence of NOLT.