Intrahepatic angiogenesis increases portal hypertension in hepatitis B patients with cirrhosis

Le Wang; Xinya Zhao; Yuemin Feng; Xiaowen Ma; Hao Wu; Qiang Zhu

doi:10.1111/hepr.12732

Intrahepatic angiogenesis increases portal hypertension in hepatitis B patients with cirrhosis

Hepatol Res. 2017 Mar;47(3):E94-E103. doi: 10.1111/hepr.12732. Epub 2016 Jun 1.

Authors

Le Wang¹, Xinya Zhao², Yuemin Feng¹, Xiaowen Ma¹, Hao Wu¹, Qiang Zhu¹

Affiliations

¹ Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
² Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

PMID: 27115574
DOI: 10.1111/hepr.12732

Abstract

Aim: It remains unclear whether intrahepatic angiogenesis increases portal hypertension (PH) in hepatitis B with cirrhosis. We aim to investigate the relationship between intrahepatic angiogenesis and PH in hepatitis B patients with cirrhosis.

Methods: Sixty hepatitis B patients with cirrhosis and 40 healthy subjects were included in this study. Angiogenesis markers vascular endothelial growth factor receptor-2 (VEGFR2), von Willebrand factor (vWF), and fibrosis marker α-smooth muscle actin (α-SMA) were observed by immunohistochemistry. Sirius Red staining was also used to determine liver fibrosis. Correlations between levels of intrahepatic angiogenesis and Child-Pugh classes, liver fibrosis degree, and portal vein pressure were examined. We also analyzed the relationship between levels of intrahepatic angiogenesis and complications of PH, including esophageal varices (EV), ascites, and hypersplenism.

Results: Correlation was observed between the levels of VEGFR2 (r = 0.590, P < 0.01), vWF (r = 0.524, P < 0.01) in tissue, and Child-Pugh classes. Significant correlations were observed between levels of VEGFR2 and α-SMA (r = 0.710, P < 0.01), VEGFR2 and Sirius Red (r = 0.841, P < 0.01), vWF and α-SMA (r = 0.768, P < 0.01), and vWF and Sirius Red (r = 0.825, P < 0.01). Patients with hepatic venous pressure gradient (HVPG) ≥12 mmHg showed higher levels of VEGFR2 and vWF expression compared to those with (HVPG) <12 mmHg (2.60 ± 1.28% vs. 1.09 ± 0.73%; 5.85 ± 2.45% vs. 2.31 ± 1.34%, P < 0.01), respectively. Moreover, complications of PH, including size of esophageal varices (P < 0.01), presence of ascites (P < 0.01), and spleen volume (P < 0.01) were significantly affected by the levels of intrahepatic angiogenesis.

Conclusion: Intrahepatic angiogenesis increases PH in hepatitis B patients with cirrhosis. The study provides the potential ways to intervene in the progresses for therapeutic benefits in cirrhosis and PH.

Keywords: intrahepatic angiogenesis; liver cirrhosis; liver fibrosis; portal hypertension; vascular endothelial growth factor recetpor-2.