The association between vitamin D status and hepatocellular carcinoma has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. ...Our objective was to investigate the association between pre-diagnostic circulating 25-hydroxyvitamin D 25(OH)D serum levels and risk of hepatocellular carcinoma in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRR) of hepatocellular carcinoma associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of pre-diagnostic 25(OH)D. Higher 25(OH)D levels were associated with a 49% reduction in the risk of hepatocellular carcinoma (highest vs. lowest tertile: multivariable IRR = 0.51, 95% confidence interval, 0.26 to 0.99; Ptrend = 0.04; per 10 nmol/L increase: IRR = 0.80, 95% confidence interval, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of pre-existing liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on Western European populations, serum levels of 25(OH)D were inversely associated with risk of hepatocellular carcinoma. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;).
Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied ...prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.
Elevated pre-diagnostic testosterone and insulin-like growth factor-I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these ...hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk (OR for top versus bottom tertile of 3.86 (1.32-11.3), ptrend =0.009). As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p=0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with pre-diagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as pre-diagnostic risk marker for HCC.
L’objectif de l’étude était d’évaluer l’acceptabilité et de décrire la perception de la vaccination contre l’herpès zoster (HZ) chez les patients ambulatoires et hospitalisés à Lyon, en France, âgés ...de 65 ans et plus. Une étude observationnelle était basée sur un questionnaire rempli lors d’une entrevue en personne de janvier 2018 à mars 2019. Les patients externes bénévoles qui ont fréquenté des laboratoires médicaux privés ou qui ont été hospitalisés dans le service de gériatrie, ou qui étaient à la clinique médicale ambulatoire pour une consultation ont été invités à participer. Au total, 907 personnes ont été interrogées, avec un âge moyen de 75,8 ans. Une grande majorité de 87,6 % (795) connaissaient le ZONA et 68,9 % (625) accepteraient d’être vaccinés contre l’AS S’ils présentaient des facteurs de risque. Les participants connaissaient le HZ en tant que maladie, mais la sensibilisation au vaccin fait encore défaut dans le grand public.
Response Trichopoulos, Dimitrios; Bamia, Christina; Lagiou, Pagona ...
JNCI : Journal of the National Cancer Institute,
2012, Letnik:
104, Številka:
21
Journal Article
BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess ...the inter-laboratory variability of these tests, and their 6 components (gamma-glutamyl transpeptidase, alanine aminotransferase, alpha2-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When gamma-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of gamma-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of gamma-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and gamma-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.
HepaRG human liver progenitor cells exhibit morphology and functionality of adult hepatocytes. We investigated the susceptibility of HepaRG hepatocytes to in vitro infection with serum‐derived ...hepatitis C virus (HCV) particles (HCVsp) and the potential neutralizing activity of the E1E2‐specific monoclonal antibody (mAb) D32.10. The infection was performed using HCVsp when the cells actively divided at day 3 postplating. HCV RNA, E1E2, and core antigens were quantified in HCV particles recovered from culture supernatants of differentiated cells for up to 66 days. The density distributions of particles were analyzed on iodixanol or sucrose gradients. Electron microscopy (EM) and immune‐EM studies were performed for ultrastructural analysis of cells and localization of HCV E1E2 proteins in thin sections. HCV infection of HepaRG cells was documented by increasing production of E1E2‐core‐RNA(+) HCV particles from day 21 to day 63. Infectious particles sedimented between 1.06 and 1.12 g/mL in iodixanol gradients. E1E2 and core antigens were expressed in 50% of HCV‐infected cells at day 31. The D32.10 mAb strongly inhibited HCV RNA production in HepaRG culture supernatants. Infected HepaRG cells frozen at day 56 were reseeded at low density. After only 1‐3 subcultures and induction of a cell differentiation process the HepaRG cells produced high titer HCV RNA and thus showed to be sustainably infected. Apolipoprotein B‐associated empty E1E2 and complete HCV particles were secreted. Characteristic virus‐induced intracellular membrane changes and E1E2 protein‐association to vesicles were observed. Conclusion: HepaRG progenitor cells permit HCVsp infection. Differentiated HepaRG cells support long‐term production of infectious lipoprotein‐associated enveloped HCV particles. The E1E2‐specific D32.10 mAb neutralizes the infection and this cellular model could be used as a surrogate infection system for the screening of entry inhibitors. (HEPATOLOGY 2011;)
Although risk factors for cirrhosis in chronic hepatitis C virus (HCV) infection have been identified, the role of HCV-genotype 3 remains controversial, and limited data are available in drug users. ...The aim of the study was to assess risk factors for severe liver disease (cirrhosis/hepatocellular carcinoma) in HCV-infected drug users between 2001 and 2007 in France. Patients who reported drug use and who had been referred for HCV infection to hepatology centers from a national surveillance system were identified. The severity of liver disease was assessed clinically and histologically (Metavir score). Factors associated with severe liver disease were analyzed after estimating missing values by multiple imputation (MI). Of the 4,065 drug users naive to anti-HCV treatment who were referred to the 26 participating centers, 8.0% had severe liver disease, 25.7% were infected with HCV-genotype 3. Factors associated independently with an increased risk of severe liver disease were HCV-genotype 3 (adjusted odds ratio, multiple imputation (aORMI) = 1.6, 95% confidence interval, 95% CI: 1.2-2.1), HIV infection (aORMI = 1.8, 1.2-2.8), male sex (aORMI = 2.0, 1.4-2.8), age over 40 years (aORMI = 2.1, 1.6-2.9), history of excessive alcohol consumption (aORMI = 2.8, 2.1-3.7), and duration of infection ≥18 years (aORMI = 2.9, 2.0-4.3). This analysis shows that HCV-genotype 3 is associated with severe liver disease in drug users, independently of age, sex, duration of infection, alcohol consumption, and co-infection with HIV. These results are in favor of earlier treatment for drug users infected with HCV- genotype 3 and confirm the need for concomitant care for excessive alcohol consumption. J. Med. Virol. 82:1647-1654, 2010. 2010 Wiley-Liss, Inc.
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