Expression of Transforming Growth Factor-α and -β in Hepatic Lobes After Hemihepatic Portal Vein Embolization

Abstract

Hemihepatic portal vein embolization (PVE) concomitantly induces atrophy in embolized and compensatory hypertrophy in nonembolized hepatic lobes. The aim of the present study was to evaluate the involvement of growth stimulatory and inhibitory factors in these hepatic lobes after PVE. Liver specimens from the embolized and nonembolized lobes of ten patients who underwent hepatectomy (8-22 days) after undergoing PVE were obtained. Proliferation and apoptosis were examined immunohistochemically using Ki-67 and the Tdt-mediated dUTP-biotin nick end-labeling method. The expression of transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta (TGF-beta) was also examined by immunohistochemical staining. PVE induced hepatocyte apoptosis in the embolized lobe and hepatocyte proliferation in the nonembolized lobe. TGF-alpha expression in the hepatocytes of the nonembolized lobe was markedly increased, whereas TGF-alpha was also overexpressed, albeit moderately, in the embolized lobe. In contrast, TGF-beta expression in the hepatocytes of the embolized lobe was significantly increased, and TGF-beta expression was also increased, although to a lesser extent, in the nonembolized lobe. The degree of volume changes of the nonembolized lobe and the embolized lobe after PVE was statistically correlated with the ratios of TGF-alpha and TGF-beta expression in these lobes (r = 0.886, P < .0001). In conclusion, these findings indicate that TGF-alpha and TGF-beta expression (assessed by immunohistochemical staining) increase in relation to hepatocyte proliferation and apoptosis, respectively, after PVE in humans and the balance of the two factors may contribute to hepatic atrophy and hypertrophy concomitantly observed in this model.

Portal Vein Embolization Before Liver Resection: A Systematic Review

“…The exact mechanisms leading to atrophy of the embolized lobe and hypertrophy of the FRL are still unknown. Recent studies have shown that in addition to the redistribution of portal blood flow PVE induces an increase in hepatic growth factor (HGF) and transforming growth factor (TGF)-α and -β, which contribute to the hypertrophy of the non-embolized lobe [60, 61]. …”

Effect of portal vein embolisation on the growth rate of colorectal liver metastases

“…Several cytokines and growth factors are known to play important roles in liver regeneration (Kusaka et al, 2006;Yokoyama et al, 2007), and could Effect of portal vein embolisation V Pamecha et al increase tumour growth after PVE. Mueller et al, reported, in a rat model of portal branch ligation, an association between hepatic atrophy and increased expression of genes known to promote tumour growth and angiogenesis (Mueller et al, 2003).…”

“…Expression of hepatocyte growth factor (HGF)-mRNA is markedly increased after portal vein ligation (Uemura et al, 2000), which is known to stimulate growth of colorectal carcinoma cells in vitro (Ueno et al, 1996;Nabeshima et al, 1998). Negative regulators of hepatocyte proliferation, such as transforming growth factor (TGF)-b1 (Braun et al, 1988;Kusaka et al, 2006), are strongly expressed in the ligated lobe (Uemura et al, 2000;Kusaka et al, 2006) and these may contribute to increased cancer-cell proliferation. The survival analysis showed excellent long-term survival in patients undergoing major liver resection for CRC metastases with Figure 3 Typical example of mitosis expression (dark brown stain) in CRC metastases for a patient who had not undergone PVE (A) compared with that post PVE (B), suggesting high cancer-cell proliferation post PVE.…”

Limits of and Complications after Embolization of the Hepatic Artery and Portal Vein to Induce Segmental Hypertrophy of the Liver: A Large Mini-Pig Study

“…The physiological triggers, which control liver regeneration and hypertrophy after PVE, are still not fully understood. It has been shown that stimulating with hepatotrophic substances - like hepatic growth factor and transforming growth factor-α and -β - contributes to hypertrophy of the non-embolized lobe [12,13]. As a second mechanism, hemodynamic changes with an upregulation of portal flow are known to regulate liver regeneration and hypertrophy.…”