Abstract

Abstract
Study background: Hepatitis C virus (HCV) is a major risk factor for the development of hepatocellular
carcinoma (HCC), however, the mechanism of hepatocarcinogenesis in HCV infection is still undefined. Chemokines,
which induce leukocyte migration and activate inflammatory/immune responses, have recently been implicated in the
regulation of tumour growth. This work was designed to study the role of macrophage inflammatory protein-1α (MIP-
1α), a potent macrophage chemo-attractant, in the development and progression of HCV-related HCC.
Methods: Thirty patients with HCV-related cirrhosis (15 patients with HCC who underwent surgical hepatic
resection and 15 patients without HCC) and 15 healthy subjects were enrolled in the study. Immunohistochemical
staining of HCC and adjacent non-neoplastic liver tissue was performed using antibodies against MIP-1α, CD68 [for
assessment of tumour-associated macrophage (TAM) count] and CD105 [for determination of microvessel density
(MVD)]. Pre-operative serum MIP-1α levels were measured using enzyme linked immunosorbant assay kit.
Results: HCV-related HCCs showed significantly higher MIP-1α expression, CD68+ TAM count and CD105-MVD
compared with adjacent non-neoplastic liver tissue. Serum MIP-1α levels were significantly higher in patients with and
without HCC than in healthy subjects and in HCC patients than in patients without HCC. The sensitivity and specificity
of serum MIP-1α in discriminating cirrhotic patients with and without HCC were 100% and 93.3% respectively at a
cut-off value of 17.5 pg/ml. The MIP-1α expression in HCCs showed positive correlations with serum MIP-1α levels;
tumour size, stage and histopathological grade; and intratumoural CD68+ TAM count and CD105-MVD. Moreover,
CD68+ TAM count had direct correlation with CD105-MVD in HCC.
Conclusion: MIP-lα plays an important role in the development and progression of HCC in chronic HCV infection,
possibly through recruitment of macrophages into tumour microenvironment and fostering tumour angiogenesis. MIPlα
may also serve as a potential serum biological marker and a useful therapeutic target in HCV-related HCC.

Keywords: Hepatocellular carcinoma; Macrophage inflammatory protein-1 alpha; Tumour-associated macrophages