1Ghada F. Helaly and 2Lobna A. Abou Shamaa
Departments of 1Microbiology and 2Immunology,
Medical Research Institute,
Infection with hepatitis C virus (HCV) is characterized by
inflammatory liver damage and a long viral persistence associated with an
increased risk of developing hepatocellular carcinoma (HCC). Intercellular
adhesion molecule-1 (ICAM-1) plays a key role during liver inflammation and
also expressed in HCC. Its cellular expression is associated with the release
of soluble form (sICAM-1) in the peripheral blood. The process of angiogenesis
plays a critical role in liver damage-associated HCV infection and in tumor
growth and metastasis. Vascular Endothelial Growth Factor (VEGF) is an
important angiogenic factor regulating tumor angiogenesis. This study aimed at
investigating the influence of HCV infection on serum profile of sICAM-1 and
VEGF in patients with hepatitis C and HCC and their diagnostic value as useful
markers reflecting progressive liver damage and development of HCC. Serum
levels of sICAM-1 and VEGF were determined in the serum of fifteen HCV infected
patients, fifteen HCV-positive patients with superimposed HCC as well as ten
healthy control subjects by enzyme linked immunosorbent assay. HCV RNA copy
numbers were analyzed by Real-time polymerase chain reaction using TaqMan probe
technology. Alpha-fetoprotein levels and serum aminotransferases activities
were also measured. The group of patients with hepatitis C and superimposed HCC
had significantly higher sICAM-1 and VEGF values than HCV infected patients
(1178.113±631.87 vs. 313.67±82.72 & 320.88±117.99 vs132.45±91.56,
p<0.001 respectively). In comparison to healthy subjects, HCV infected
patients showed dramatically elevated serum levels of VEGF (132.45±91.56 vs.
7.76±7.41, p<0.001). On the other hand, sICAM-1 levels were elevated in
patients with HCV as compared with healthy controls, but this did not reach
statistical significance (313.67±82.72 vs.230.3±47.4, p>0.05). A highly
significant correlation was found between VEGF and sICAM-1 levels in all patients(r=0.731,
p<0.001) also between VEGF, sICAM-1 and AFP(r=0.473, p<0.001, r= 0.690,
p<0.001, respectively) as well as between sICAM-1 and AST
activities(r=0.367, p<0.05). A weak correlation was found between the level
of viremia and VEGF, sICAM-1 levels, yet this did not reach statistical
significance (r =0.312, p=0.09&r =0.228, p>0.05 respectively). The sensitivity of HCC detection using AFP
alone was 93.3%. It yielded 100% detection sensitivity when combined with
sICAM-1 and/or VEGF with diagnostic accuracy reaching 96.67%. In
conclusion, HCV infection and the development of HCC on top greatly affect the
serum profile of VEGF and sICAM-1. VEGF as it stimulates endothelial cell
growth, it could modulate the expression of sICAM-1 and both could be considered
as convenient markers of progressive liver damage, endothelial activation and
therefore could improve detection and management of HCC.