Increased HCMV seroprevalence in patients with hepatocellular carcinoma.
BACKGROUND
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. 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.


METHODS
First, 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.


RESULTS
We 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.


CONCLUSIONS
Our 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.
Department of Virology, University of Franche-Comte, EA 4266, IFR 133 INSERM, CHU Besancon, F-25030 Besançon, France.
Quentin
Q
Lepiller
Manoj K
MK
Tripathy
Vincent
V
Di Martino
Bernadette
B
Kantelip
Georges
G
Herbein
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000453:epidemiology* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D060085:Coinfection; D015897:Comorbidity; D003587:Cytomegalovirus / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000453:epidemiology*; D005260:Female; D005602:France / Q000453:epidemiology; D016174:Hepacivirus / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000302:isolation & purification; D006785:Hospitals, University; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016036:Seroepidemiologic Studies
D015850:Interleukin-6