UDP-glucuronosyltransferase UGT1A7 genetic polymorphisms in hepatocellular carcinoma: a differential impact according to seropositivity of HBV or HCV markers?

<p>Abstract</p> <p>Background:</p> <p>We conducted a case-control study to evaluate the role of UDP-glucuronosyltransferase 1A7 (UGT1A7) polymorphisms in the onset of hepatocellular carcinoma (HCC).</p> <p>Methods:</p> <p>The study included 165 patients with HCC, 134 with cirrhosis and 142 controls without liver disease, matched for age and hospital. All were men younger than 75 years. HCC and cirrhosis patients were stratified according to time since cirrhosis diagnosis.</p> <p>Results:</p> <p>We found a positive association between the UGT1A7*3/*3 genotype and HCC when the comparison was restricted to patients whose disease was of viral origin [OR = 3.4 (0.3–45)] but a negative association when it included only alcoholic patients [OR = 0.1 (0.02–0.6), p = 0.01].</p> <p>Conclusion:</p> <p>Our study shows that UGT1A7 may play a role in hepatocellular carcinogenesis and that this role may differ according to the primary cause of the cirrhosis.</p

Bile Acids Specifically Increase Hepatitis C Virus RNA-Replication

<div><h3>Background</h3><p>Hepatitis C virus (HCV) patients with high serum levels of bile acids (BAs) respond poorly to IFN therapy. BAs have been shown to increase RNA-replication of genotype 1 but not genotype 2a replicons. Since BAs modulate lipid metabolism including lipoprotein secretion and as HCV depends on lipids and lipoproteins during RNA-replication, virus production and cell entry, BAs may affect multiple steps of the HCV life cycle. Therefore, we analyzed the influence of BAs on individual steps of virus replication.</p> <h3>Methods</h3><p>We measured replication of subgenomic genotype (GT) 1b and 2a RNAs as well as full-length GT2a genomes in the presence of BAs using quantitative RT-PCR and luciferase assays. Cell entry was determined using HCV pseudoparticles (HCVpp). Virus assembly and release were quantified using a core-specific ELISA. Replicon chimeras were employed to characterize genotype-specific modulation of HCV by BAs. Lunet CD81/GFP-NLS-MAVS cells were used to determine infection of Con1 particles.</p> <h3>Results</h3><p>BAs increased RNA-replication of GT1b replicons up to 10-fold but had no effect on subgenomic GT2a replicons both in Huh-7 and HuH6 cells. They did not increase viral RNA translation, virus assembly and release or cell entry. Lowering replication efficiency of GT2a replicons rendered them susceptible to stimulation by BAs. Moreover, replication of full length GT1b with or without replication enhancing mutations and GT2a genomes were also stimulated by BAs.</p> <h3>Conclusions</h3><p>Bile acids specifically enhance RNA-replication. This is not limited to GT1, but also holds true for GT2a full length genomes and subgenomic replicons with low replication capacity. The increase of HCV replication by BAs may influence the efficacy of antiviral treatment in vivo and may improve replication of primary HCV genomes in cell culture.</p> </div

Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study

BACKGROUND/AIMS—A study was undertaken of liver biopsy samples from 229 consecutive patients with alcoholic or hepatitis C virus related cirrhosis who were prospectively followed until January 1996 to evaluate the influence of liver iron content on survival and the occurrence of hepatocellular carcinoma.
METHODS—Hepatic iron content was measured with a validated semiquantitative score, and its predictive value for survival and the occurrence of hepatocellular carcinoma was assessed.
RESULTS—130 patients had detectable iron at enrolment. During follow up (57 (28) months), 95 patients died and 39 patients developed hepatocellular carcinoma. No significant relation was found between hepatic iron and the occurrence of hepatocellular carcinoma. Conversely, the presence of iron was predictive of death in alcoholic patients (p = 0.007) by the log rank test but not in patients with hepatitis C virus related (p = 0.71) or mixed (p = 0.98) cirrhosis. The predictive value of hepatic iron content in patients with alcoholic cirrhosis was confirmed by the Cox model using either a binary coding (p = 0.009; relative risk = 2.27; 95% confidence interval 1.2 to 4.19) or the continuous values (p = 0.002).
CONCLUSIONS—These results suggest that hepatic iron enhances liver lesions caused by alcohol but not those caused by hepatitis C virus.


Keywords: cirrhosis; liver; iron; survival; hepatocellular carcinoma; alcoho

Identification of serum proton NMR metabolomic fingerprints associated with hepatocellular carcinoma in patients with alcoholic cirrhosis

International audiencePurpose Metabolomics depicts metabolic changes in biologic systems using a multiparametric analysis technique. This study assessed the metabolomic profiles of serum, obtained by proton nuclear magnetic resonance (NMR) spectroscopy, from cirrhotic patients with and without hepatocellular carcinoma (HCC). Experimental Design The study included 154 consecutive patients with compensated biopsy-proven alcoholic cirrhosis. Among these, 93 had cirrhosis without HCC, 28 had biopsy-proven HCC within the Milan criteria and were eligible for curative treatment (small HCC), and 33 had HCC outside the Milan criteria (large HCC). Proton spectra were acquired at 500 MHz. An orthogonal partial latent structure [orthogonal projection to latent structure (OPLS)] analysis model was built to discriminate large HCC spectra from cirrhotic spectra. Small HCC spectra were secondarily projected using previously built OPLS discriminant components. Results The OPLS model showed discrimination between cirrhotic and large HCC spectra. Metabolites that significantly increased with large HCC were glutamate, acetate, and N-acetyl glycoproteins, whereas metabolites that correlated with cirrhosis were lipids and glutamine. Projection of small HCC samples into the OPLS model showed a heterogeneous distribution between large HCC and cirrhotic samples. Small HCC patients with metabolomic profile similar to those of large HCC group had higher incidences of recurrence or death during follow-up. Conclusions Serum NMR-based metabolomics identified metabolic fingerprints that could be specific to large HCC in cirrhotic livers. From a metabolomic standpoint, some patients with small HCC, who are eligible for curative treatments, seem to behave as patients with advanced cancerous disease. It would be useful to further prospectively investigate these patients to define a subgroup with a worse prognosis. ©2012 AACR

Bone mineral density assessed by dual-energy X-ray absorptiometry in patients with viral or alcoholic compensated cirrhosis. A prospective study.

International audienceBackground/aim: Cirrhosis is considered as a risk factor for osteoporosis whose prevalence is poorly known. The aim was to assess prospectively bone mineral density (BMD) in patients with alcoholic or viral compensated cirrhosis. Methods: From 2006 to 2008, patients with viral or alcoholic compensated cirrhosis had BMD assessment by dual-energy X-ray absorptiometry. The prevalence of osteopenia (-2.5 SD < T-score < -1 SD) and osteoporosis (T-score <= -2.5 SD), and the influence of age, gender and aetiology of cirrhosis were assessed using univariate and multiple regression analysis. Results: One hundred and nine patients were studied (72 men, 55.3 +/- 11.4 years and 37 women, 65.2 +/- 11.0); with HBV (n = 35), HCV (n = 43), or alcoholic cirrhosis (n = 31). At the lumbar spine, 25 patients had osteopenia and 12 had osteoporosis. At the femoral site, 23 had osteopenia and 4 had osteoporosis. Female gender had an independent decreased effect on the total BMD. Conclusions: The prevalence of osteoporosis was up to 11% at the lumbar spine, greater in women independently of age, without significant difference according to the aetiology of cirrhosis. (C) 2011 Elsevier Masson SAS. All rights reserved