Long-term consequence of rat orthotopic liver transplantation with and without hepatic arterial reconstruction: a...

Our aim was to investigate the time-related changes in various parameters following orthotopic rat liver transplantation with (AOLT) and without (NOLT) arterial reconstruction in male Lewis rats. Body weight and biochemical parameters were measured weekly, and a liver biopsy was obtained at 4, 8, and 12 weeks. Hemodynamics were evaluated at 12 weeks using the microsphere technique and compared with matched controls. Following AOLT, rats gained weight normally without any noticeable complication. In NOLT, two subgroups (NOLT-1 and NOLT-2) could clearly be identified retrospectively. In the NOLT-1 group, the body weight increased normally, although animals presented transient cholestasis. In these rats, the ductular proliferation found at 4 weeks had regressed by the 12th week with near-normal biopsies. By contrast, in the NOLT-2 group, rats did not gain body weight and had persistent cholestasis. Marked ductular proliferation with increasing fibrosis was observed, resulting in a secondary biliary cirrhosis by the 12th week. Surprisingly, rearterialization of the grafted liver occurred in both NOLT-1 and NOLT-2 irrespective of their clinical course. All transplanted rats showed portal hypertension with marked portosystemic shunts, probably caused by the portal cuff. However, a hyperdynamic circulatory state was only observed in the NOLT-2 group with cirrhotic changes. These findings further show the combined role of an intact hepatic innervation and of hepatocellular insufficiency in the genesis of the hyperdynamic circulatory state associated with portal hypertension.