The effect of extrahepatic cholestasis on liver regeneration after partial hepatectomy in the rat.

Liver regeneration after partial hepatectomy was studied in four groups of rats: control rats (n = 12), rats with 1 week of common bile duct obstruction (n = 11), rats with restoration of bile flow after 1 week of obstruction (n = 9) and a sham-operated group (n = 7). Parameters of DNA synthesis--thymidine kinase activity and in vivo bromodeoxyuridine incorporation--were measured at partial hepatectomy (T = 0), and 24 and 48 h after partial hepatectomy. During common bile duct obstruction, DNA synthesis was already stimulated at T = 0, but partial hepatectomy in common bile duct obstruction rats induced a delayed DNA synthesis. After 1 week of restoration of bile flow, normal DNA synthesis had returned at T = 0, but DNA synthesis after partial hepatectomy was still delayed. The sham-operated rats showed a normal regeneration response after partial hepatectomy assessed by bromodeoxyuridine incorporation but delayed as assessed by thymidine kinase activity, partly due to the impaired physical condition of the animals. The present data support the hypothesis that during cholestasis, regeneration promoting, and inhibitory factors accumulate in the liver, their balance determining whether regeneration after partial hepatectomy will occur in a normal, enhanced or delayed way.