Liver angiogenesis as a risk factor for hepatocellular carcinoma development in hepatitis C virus cirrhotic patients

Abstract

AIM:To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients. METHODS:One hundred-five patients (69 males, 36 females; age range, 51-90 year; median 66 year) with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 mo. Angiogenesis was assessed by using microvessel density (MVD), hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies. RESULTS:Forty six patients (43.8%) developed HCC after a median time of 55 (6-120) mo while 59 (56.2%) did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low (median MVD = 3; range 0-20) and high (median MVD = 7; range 1-24) MVD was statistically significant (χ 2 = 22.06; P < 0.0001) which was not the case for MIB1 or PCNA (MIB-1: χ 2 = 1.41; P = 0.2351; PCNA: χ 2 = 1.27; P = 0.2589). The median MVD was higher in patients who developed HCC than in those who did not. HCC-free interval was significantly longer in patients with the MVD ≤ 4 (P = 0.0006).No relationship was found between MIB1 or PCNA and MVD (MIB-1 r 2 = 0.00007116, P = 0.9281; PCNA: r 2 = 0.001950; P = 0.6692). MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk. CONCLUSION:Liver angiogenesis has a role for in HCVrelated liver carcinogenesis and for defining patients at higher risk.

Effect of Long-term Propranolol Treatment on Hepatocellular Carcinoma Incidence in Patients with HCV-Associated Cirrhosis

“…Indeed, high hepatic level of 8-hydroxy-2 0 -deoxyguanosine (marker of DNA damage induced by oxidative stress), as well as histologic markers of liver angiogenesis are associated with a higher incidence of HCC in patients with HCV cirrhosis (4,5). In liver, HCV proteins induce NADPH oxidase 4 expression and subsequent reactive oxygen species (ROS) production through an autocrine TGFb-dependent mechanism, trigger mitochondrion-derived ROS and angiogenesis (6)(7)(8).…”

Hepatocellular carcinoma: Epidemiology and clinical aspects

“…Moreover, HCV-positive sera and liver homogenates enhanced proliferation and migration of endothelial cells compared with controls and HBVpositive patients (Mazzanti et al, 1997). According to these data, it has been recently demonstrated that liver angiogenesis, estimated by the microvessel density in liver biopsies of patients affected by HCV-related liver cirrhosis, can be predictive of the occurrence of HCC (Mazzanti et al, 2007).…”

DNMT1-Induced miR-378a-3p Silencing Promotes Angiogenesis via NF-κB Signaling Pathway by Targeting TRAF1 in Hepatocellular Carcinoma

“…Low expression of MVD was for scores from 0 to 3. The ones with scores ≥ 4 were considered high MVD [29].…”