Dataset Information

Increased HCMV seroprevalence in patients with hepatocellular carcinoma.

ABSTRACT:

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.

SUBMITTER: Lepiller Q

PROVIDER: S-EPMC3224784 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Publications

Increased HCMV seroprevalence in patients with hepatocellular carcinoma.

Lepiller Quentin Q Tripathy Manoj K MK Di Martino Vincent V Kantelip Bernadette B Herbein Georges G

Virology journal 20111027

<h4>Background</h4>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 stu ...[more]

PMID: 22032643

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Project description:Background & aimsHepatocellular carcinoma (HCC) screening of patients with cirrhosis is recommended by professional societies to increase detection of early stage tumors and survival, but is underused in clinical practice.MethodsWe conducted a retrospective cohort study of 13,714 patients diagnosed with HCC from 2003 through 2013 included in the Surveillance, Epidemiology, and End Results Program-Medicare database. We characterized receipt of HCC screening in the 3 years before HCC diagnosis using mutually exclusive categories (consistent vs inconsistent vs no screening) and the proportion of time covered with screening. Correlates for screening receipt were assessed using a multivariable 2-part regression model. We examined the association between screening receipt and early detection of tumors using multivariable logistic regression. We evaluated associations between screening receipt and overall survival using a Cox proportional hazards model, after adjustments for effects of lead-time bias and length-time bias on survival rate estimators.ResultsMost patients with cirrhosis (51.1%) did not receive any screening in the 3 years before a diagnosis of HCC, and only 6.8% of patients underwent consistent annual screening. The proportion with consistent screening increased from 5.4% in 2003 to 2006 to 8.8% in 2011 to 2013 (P < .001). The mean proportion of time covered was 13.4% overall, which increased from 11.7% in 2003 to 2006 to 15.2% in 2011 to 2013. Receipt of consistent screening was associated with detection of early stage tumors (odds ratio, 1.98; 95% CI, 1.68-2.33) and a reduced risk of death after correction for lead-time bias (hazard ratio, 0.76; 95% CI, 0.70-0.83). Inconsistent screening was associated with a slightly smaller increase in early detection of HCC (odds ratio, 1.31; 95% CI, 1.20-1.43) and a reduced risk of death (hazard ratio, 0.86; 95% CI, 0.83-0.90). After correction for lead- and length-time biases, higher proportions of patients with consistent (23%; 95% CI, 21%-25%) and inconsistent screening (19%; 95% CI, 19%-20%) survived for 3 years compared with patients without screening (13%; 95% CI, 12%-14%).ConclusionsIn an analysis of the Surveillance, Epidemiology, and End Results Program-Medicare database, we found HCC screening to be underused for patients with cirrhosis. This contributes to detection of liver tumors at later stages and shorter times of survival. However, the proportion of patients screened for HCC has increased over time.

Project description:BACKGROUND:Hepatocellular carcinoma (HCC) is a frequent type of primary liver cancer, and its prevalence is increasing worldwide. Indeed, the underlying molecular mechanism is not well understood. Previous studies have shown evidence that tight junction (TJ) components were correlated with carcinogenesis and tumor development. Our aims were to determine the serum levels of tight junction protein Zonula Occludens (ZO)-1 and an inflammatory marker such as high-sensitive C-reactive protein (hs-CRP) in HCC patients compared to healthy volunteers and also to identify the association between ZO-1 and inflammation in HCC. METHODS:Thirty HCC patients and 30 healthy volunteers were recruited in the current study. Clinical data regarding child class, BCLC staging, the number of lesions, tumor size, absence or presence of metastasis, cirrhosis and hepatitis infection were also collected in HCC patients. Plasma ZO-1 and serum hsCRP were analyzed by EIA and ELISA respectively and biochemical parameters by autoanalyser (AU680 Beckman Coulter, USA). Furthermore, hepatic ZO-1 protein expression and tissue localization were examined. RESULTS:Compared to healthy individuals, the serum levels of bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) were elevated significantly (P?<?0.0001) whilst serum albumin level was significantly (P?<?0.0001) decreased in HCC patients. Furthermore, tight junction protein ZO-1 concentration was significantly elevated in HCC patients compared to control subjects (648?±?183.8 vs. 396.4?±?135.8 pg/ml, respectively; P?<?0.0001). Serum hsCRP level was also significantly increased in HCC patients compared to control subjects (17.25?±?3.57 vs. 5.54?±?2.62 mg/L, respectively; P?<?0.0001). Moreover, decreased protein expression of ZO-1 was found in liver tissue obtained from HCC patients. CONCLUSION:Our findings show for the first time that the systemic concentration of ZO-1 was significantly elevated in HCC patients and is positively correlated with inflammatory markers. Thus, the current study showing evidence that inflammation promotes plasma ZO-1 concentration and raises the possibility that it could be used as a potential diagnostic biomarker for HCC progression.

Dataset Information

Increased HCMV seroprevalence in patients with hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

Increased HCMV seroprevalence in patients with hepatocellular carcinoma.

Similar Datasets

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