Portal vein branch occlusion induces cell proliferation of cholestatic rat liver.

Portal vein branch occlusion induces atrophy of occluded hepatic lobes, concomitantly associated with the complementary hypertrophy of unoccluded lobes. In this context, selective embolization of the portal vein branch supplying the area to be resected has been performed prior to extended hepatectomy to reduce the risk of postoperative liver failure. However, carcinoma of the hepatic hilus is often associated with obstructive jaundice. At present it is still obscure whether cholestatic hepatocytes can also respond well to the proliferation stimuli caused by the portal vein branch embolization. To clarify this point, we made a rat model of portal vein branch ligation in combination with cholestasis. As an indicator of proliferation, we determined the activity of DNA polymerase alpha and the mitotic index. The results demonstrate that, even in the cholestatic liver, the expression of DNA polymerase alpha in unoccluded lobes was induced by contralateral portal vein branch ligation. The maximal degree of DNA polymerase alpha induction in the cholestatic liver was similar to that in the noncholestatic liver, i.e., fivefold above that in the resting liver. The level of DNA polymerase alpha activity correlated well with the mitotic index in the same tissue. Furthermore, the cell proliferation after the portal vein branch occlusion is not suppressed by the preceding external biliary drainage, which had been shown to suppress the liver regeneration after partial hepatectomy. From these results, it is concluded that portal vein branch ligation induces liver cell proliferation in unoccluded lobes, irrespective of the presence of cholestasis.