Abstract
BackgroundHepatocellular carcinoma (HCC) is the most common primary liver cancer, usually arising after years of chronic liver inflammation that could result from viral infections such as hepatitis B virus (HBV) and hepatitic C virus (HCV) infections. Human cytomegalovirus (HCMV) infects primary human hepatocytes and remains an important cause of morbidity in immunocompromised persons where it may manifest as symptomatic end-organ disease including hepatitis. The goal of the present study was to determine a potential correlation between HCMV infection and the appearance of HCC.MethodsFirst, we analyzed the seroprevalence of HCMV in a cohort of 11,318 patients hospitalized between 2003 and 2009 in different departments of a French University Hospital. Second, we studied HCMV seroprevalence in a cohort of 190 subjects who were stratified on the basis of age, gender, HCC, cirrhosis (Cir), and the exposition to hepatotropic viruses (HCV, HBV). We further determined whether HCMV DNA was present specifically in tumour area in liver biopsies from HCC-positive patients by using nested PCR.ResultsWe found that the HCMV seroprevalence was high in the Hepatology department. The HCMV seroprevalence was significantly higher in patients infected with HCV and/or HBV than in patients who were not infected by those later viruses (76.2% versus 56.5%, p < 0.001). The HCMV seroprevalence was significantly higher in patients with HCC (74%) and lower in patients without HCC (54% for HCC-/Cir+ patients, 57% for HCC-/Cir- subjects). We observed a positive correlation between serum IL-6 levels and HCMV seroprevalence in cirrhotic patients, but not in HCC patients. Serum IL-6 levels correlated positively with C-reactive protein (CRP) levels. Preliminary histological studies from liver biopsies from HCC-positive patients highlighted that HCMV DNA can be detected in tumour area of some of the patients studied.ConclusionsOur results indicate that HCMV seroprevalence in patients with HCC is significantly higher than in patients without HCC, is positively correlated with serum IL-6 levels in cirrhotic patients, and is positively associated with the presence of other hepatotropic viruses such as HCV and HBV.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, usually arising after years of chronic liver inflammation that could result from viral infections such as hepatitis B virus (HBV) and hepatitic C virus (HCV) infections
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections can lead to HCC, whereas non-infectious inflammatory states, such as chronic inflammation induced by alcohol consumption and hereditary iron overload can contribute to HCC
The Human cytomegalovirus (HCMV) seroprevalence was significantly higher in patients infected with HCV and/or HBV than in patients who were not infected by those later viruses (76.2% versus 56.5%, p < 0.001) (Table 2)
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, usually arising after years of chronic liver inflammation that could result from viral infections such as hepatitis B virus (HBV) and hepatitic C virus (HCV) infections. Hepatocellular carcinoma (HCC) is the most common primary liver cancer, usually arising after years of chronic liver inflammation. Human cytomegalovirus (HCMV) is an opportunistic, species-specific herpesvirus that infects a large part of the population worldwide and causes asymptomatic latent infection in healthy subjects. It can cause severe disease in the absence of an effective immune response, especially in patients with AIDS and in immunocompromised solid-organ and bone marrow allograft recipients [8]. Virion binding activates multiple intracellular signal transduction pathways, including the phosphatidylinositol kinase, MAPK/ERK and protein kinase C pathways, all of which lead to the activation of nuclear factors such as NF-kB and p38 [18,19], which are known inducers of IL-6 gene transcription [20]
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