Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a lower prevalence of steatosis in patients with type 2 diabetes

Summary Background & aims Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome and type 2 diabetes. Although dietary fat contributes substantially to the accumulation of liver fat, the role of individual fatty acids in this accumulation is unclear. Objective In this study, we set out to determine whether liver fat content (LFC), was associated with red blood cell fatty acid (RBC-FA) composition in people with type 2 diabetes. Design, settings, and participants One hundred and sixty-two type 2 diabetic patients were included in this study. LFC was measured using 1H-MR Spectroscopy. RBC-FA composition was measured by gas chromatography. Results One…

Clinical and economic impact of drug eluting beads in transarterial chemoembolization for hepatocellular carcinoma

Summary What is known and objective Drug eluting beads (DEBs) theoretically improve the efficacy and safety of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Nonetheless, their economic profile has not been assessed. Our retrospective before/after study aimed to compare efficacy, safety and economic profile of two strategies of TACE without (Period 1) or with the possibility of using DEBs (Period 2). Methods All HCC patients treated by TACE in our hospital between March 2006 and May 2013 were included. Economic analyses were performed from the French Public Health Insurance point of view according to the French Diagnosis-Related Group prospective payment system an…

Idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma: results of the IDASPHERE phase I trial

SummaryBackground A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC). Aim To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life. Methods Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300–500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients. Results Twenty-one patients were enrolled, inclu…

Dietary components modulate the risk of hepatocellular carcinoma in cirrhotic patients.

Abstract Eighty percent of hepatocellular carcinoma (HCC) cases occur after cirrhosis from various etiologies. The association between diet and cancer is well accepted, but the links with cirrhosis progression and HCC risk have been poorly investigated. However, we hypothesized that diet could be a modifiable preventive factor for HCC. Thus, the aim of our study was to explore the relationships between dietary factors and the risk of HCC in a population of cirrhotic patients. A total of 582 cirrhotic patients were studied: 401 without HCC (controls) and 181 with HCC (cases). These patients were recruited between 2008 and 2012 for the “CiRCE” case-control study conducted in six French univer…

Application of the new eLIFT test for the non-invasive diagnosis of advanced liver fibrosis in people with type 2 diabetes

PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes

Context: Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance. Objective: In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in unselected patients with type 2 diabetes. Design, setting and participants: Two hundred and thirty-four patients with type 2 diabetes were included in this study. Main outcome measures: LFC was evaluated using 1H-MR spectroscopy; fibrosis was measured using the non-invasive FibroTest®. Results: Advanced liver fibrosis (stage F2 or above) was o…

Triple therapy in treatment-experienced patients with HCV-cirrhosis in a multicentre cohort of the French Early Access Programme (ANRS CO20-CUPIC) – NCT01514890

International audience; Background & AimsIn phase III trials, the safety profile of triple therapy (pegylated interferon/ribavirin with boceprevir or telaprevir) seems to be similar in HCV treatment-experienced cirrhotic and non-cirrhotic patients, but few cirrhotics were included. We report the week 16 safety and efficacy analysis in a cohort of compensated cirrhotics treated in the French Early Access Programme.Methods674 genotype 1 patients, prospectively included, received 48 weeks of triple therapy. The analysis is restricted to 497 patients reaching week 16.ResultsA high incidence of serious adverse events (40.0%), and of death and severe complications (severe infection or hepatic dec…

Effectiveness of telaprevir or boceprevir in treatment-experienced patients with HCV genotype 1 infection and cirrhosis. : Triple therapy in HCV genotype 1 cirrhotics

International audience; BACKGROUND & AIMS: We investigated the effectiveness of the protease inhibitors peginterferon and ribavirin in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis. METHODS: In the Compassionate Use of Protease Inhibitors in Viral C Cirrhosis study, 511 patients with HCV genotype 1 infection and compensated cirrhosis who did not respond to a prior course of peginterferon and ribavirin (44.3% relapsers or patients with viral breakthrough, 44.8% partial responders, and 8.0% null responders) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks. We assessed percentages of patients with sustained viral respo…

A 30-Year, Population-Based Study Shows Improved Management and Prognosis of Hepatocellular Carcinoma

Background & Aims Little is known about the impact of changes in the management of hepatocellular carcinoma (HCC) over time. We assessed trends in the pattern of care and in prognosis at a population level. Methods Data on diagnostic conditions, treatment, and prognosis from 1976–2005 were collected by the population-based digestive cancer registry of Burgundy (France). A nonconditional logistic regression was used to identify factors associated with treatment for cure. A multivariate relative survival analysis was also performed. Results The context of HCC diagnosis has changed; the proportion of asymptomatic patients increased from 5.6% (1976–1985) to 37.2% (1996–2005). The proportion of …

Type 1 diabetes is not associated with an increased prevalence of hepatic steatosis

Aim Non-alcoholic fatty liver disease (NAFLD) is commonly associated with Type 2 diabetes. Recently, it has been suggested that NAFLD is also frequently associated with Type 1 diabetes and diabetic complications. In this study, we set out to determine whether Type 1 diabetes was associated with liver fat content measured using magnetic resonance imaging. Methods One hundred and twenty-eight patients with Type 1 diabetes, 264 patients with Type 2 diabetes and 67 participants without diabetes were included in this study. Hepatic steatosis was defined as a liver fat content > 5.5%. Results People with Type 1 diabetes and controls were similar for age and BMI. Liver fat content was significantl…

Hepatitis E virus-induced primary cutaneous CD30(+) T cell lymphoproliferative disorder.

International audience; BACKGROUND & AIM:Several types of unexplained extra-hepatic manifestations, including haematological disorders, have been reported in the context of hepatitis E virus (HEV) infection. However, the underlying mechanism(s) of these manifestations are unknown. We provide evidence that HEV has an extra-hepatic endothelial tropism that can engage cutaneous T cells towards clonality.METHODS:A patient with a CD30(+) cutaneous T cell lymphoproliferative disorder (T-LPD) and biopsy-proven chronic HEV infection received three rounds of oral ribavirin treatment, administered either without or with interferon, and eventually achieved a sustained virologic response (SVR). Patholo…

Potentiel inflammatoire de l’alimentation et risque de carcinome hépatocellulaire chez des patients atteints de cirrhose

Introduction et but de l’etude La repetition d’episodes inflammatoires de plusieurs origines (virales, alcooliques, metaboliques) conduisant a la cirrhose sont sans doute des causes majeures de carcinogenese hepatique. La relation entre alimentation et carcinome hepatocellulaire (CHC) sur cirrhose a encore ete peu exploree. Notre objectif etait d’examiner l’association entre le potentiel inflammatoire de l’alimentation (evalue par Dietary Inflammatory Index, DII) et le risque de CHC chez des patients cirrhotiques. Materiel et methodes Dans l’etude multicentrique CiRCE (Cirrhose et Risque de Carcinome hepatocellulaire dans le grand Est), 181 patients cirrhotiques avec CHC (cas) et 401 patien…

Intravoxel incoherent motion diffusion-weighted imaging in nonalcoholic fatty liver disease: a 3.0-T MR study.

International audience; PURPOSE: To compare pure molecular diffusion, D, perfusion-related diffusion, D*, and perfusion fraction, f, determined from diffusion-weighted (DW) magnetic resonance (MR) imaging on the basis of the intravoxel incoherent motion (IVIM) theory in patients with type 2 diabetes with and without liver steatosis. MATERIALS AND METHODS: This prospective study was approved by the appropriate ethics committee, and written informed consent was obtained from all patients. Between December 2009 and September 2011, 108 patients with type 2 diabetes (51 men, 57 women; mean age, 50 years) underwent 3.0-T single-voxel point-resolved proton MR spectroscopy of the liver (segment VII…

Randomised controlled trial of lipiodol transarterial chemoembolisation with or without amiodarone for unresectable hepatocellular carcinoma.

Abstract Background There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma. Aim The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group. Methods Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions. Results Thirteen patients were randomised in the amiodarone group, and 14 we…

Potential role of oxidative DNA damage in the impact of PNPLA3 variant (rs 738409 CG) in hepatocellular carcinoma risk.

International audience

Impact économique de la chimioembolisation avec microsphères chargées dans le traitement du carcinome hépatocellulaire

Resume La chimioembolisation est le traitement de premiere ligne pour les patients atteints d’un carcinome hepatocellulaire (CHC) non resecable, non metastatique. Les microspheres chargees d’anticancereux recemment commercialisees ont pour objectif d’augmenter l’efficacite de la chimioembolisation en permettant un relargage controle et prolonge de l’anticancereux au plus proche de la tumeur. Notre etude monocentrique compare selon deux methodes de valorisation, les couts medicaux hospitaliers directs d’une premiere cure de chimioembolisation conventionnelle et d’une premiere cure de chimioembolisation avec microspheres chez 30 patients atteints de CHC. Le cout moyen valorise par la comptabi…

Impact pronostique de la concentration de 3-hydroxymyristate sur la survie des patients atteints de cirrhose alcoolique ou virale

Etat de la question Le role de l’endotoxemie liee a la translocation bacterienne sur l’aggravation de la cirrhose fait l’objet de nombreuses etudes, mais son impact sur la mortalite au cours de la cirrhose est mal connu. Le but de ce travail etait d’etudier l’impact de la concentration sanguine de 3-hydroxymyristate (3-HM) total (composant specifique des lipopolysaccharides, endotoxine), sur le risque de deces et de complications des malades cirrhotiques. Materiel et methodes Au total, 593 patients atteints de cirrhose alcoolique ou virale, sans carcinome hepatocellulaire ont ete inclus entre 2008 et 2012 dans six centres hospitalo-universitaires francais. Le dosage de 3-HM total, libre et …

Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents.

Abstract Purpose. A better identification of patients who are more likely to benefit from vascular endothelial growth factor–targeted therapy is warranted in metastatic renal cell carcinoma (mRCC). As adipose tissue releases angiogenic factors, we determined whether parameters such as visceral fat area (VFA) were associated with outcome in these patients. Experimental Design. In 113 patients with mRCC who received antiangiogenic agents (bevacizumab, sunitinib, or sorafenib) (n = 64) or cytokines (n = 49) as first-line treatment, we used computed tomography to measure VFA and subcutaneous fat area (SFA). We evaluated associations linking body mass index (BMI), SFA, and VFA to time to progres…

Liver methylene fraction by dual- and triple-echo gradient-echo imaging at 3.0T: Correlation with proton MR spectroscopy and estimation of robustness after SPIO administration

Purpose To assess the systematic errors in liver methylene fraction (LMF) resulting from fat–fat interference effects with dual- and triple-echo gradient-recalled-echo Dual/Triple GRE) sequences and to test the robustness of these sequences after iron overloading. Materials and Methods Forty type-2 diabetic patients underwent LMF measurement by 3.0T 1H magnetic resonance spectroscopy (corrected for T1 and T2 decays) as the reference standard and liver fat fraction (%Fat) measurement by four Dual/Triple GRE sequences with 20° and 60° flip angle (α), corrected for T1 recovery. The same four sequences were repeated in eight patients after ferumoxide injection. Corrections for systematic errors…

Predictive factors of transarterial chemoembolisation toxicity in unresectable hepatocellular carcinoma

Abstract Background Transarterial chemoembolisation (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity. Aim To identify predictive factors of severe TACE-related toxicity in patients with unresectable HCC. Methods All HCC patients who underwent TACE at the Dijon University Hospital between 2008 and 2011 were included in this retrospective study. Severe TACE-related toxicity was defined as the occurrence of any adverse event grade ≥4, or any adverse event that caused a prolongation of hospitalisation of >8 days, or any additional hospitalisation within 1 month after TACE. Factors predicting toxicity were identified using a logistic…

Résultat et coût de la chimioembolisation hépatique avec des billes chargées chez 21 patients

Resume Objectif L’objectif de notre travail est d’evaluer le resultat et le cout global d’une strategie de traitement des patients atteints d’un carcinome hepatocellulaire (CHC) non resecable non metastatique par chimioembolisation (CHE) avec billes chargees. Patients et methodes L’ensemble des patients traites par CHE avec billes chargees pour un CHC entre janvier 2009 et decembre 2010 dans notre etablissement a ete inclus dans l’etude. Tous les patients etaient traites selon une strategie « a la demande » avec evaluation apres chaque cure de CHE. Resultats Vingt et un patients ont recu en moyenne 1,3 cures. La mediane de temps jusqu’a arret du traitement et la mediane de survie sans progr…

Result and cost of hepatic chemoembolisation with drug eluting beads in 21 patients.

Abstract Purpose The aim of our study was to assess the results and cost of a treatment strategy involving transarterial chemoembolisation with drug eluting beads (DEB-TACE) in patients with unresectable non-metastatic hepatocellular carcinoma (HCC). Patients and methods This study included all patients treated with DEB-TACE in our hospital between January 2009 and December 2010. All patients received DEB-TACE on demand and were evaluated after each session. Results Twenty-one patients received an average of 1.3 sessions. The median time to treatment discontinuation and median progression-free survival was 181 days and 295 days, respectively. Toxicity caused treatment discontinuation in thr…

Facteurs nutritionnels et risque de carcinome hépatocellulaire chez des personnes atteintes de cirrhose

Introduction et but de l’etude Le carcinome hepatocellulaire (CHC) se developpe dans 80 % des cas sur un foie cirrhotique. En France, l’incidence augmente et les traitements restent peu efficaces. L’alimentation peut etre un moyen de prevention interessant mais les resultats d’etudes dans ce domaine restent rares et divergents. Notre objectif etait donc d’etudier les liens entre differents facteurs alimentaires et le risque de CHC dans une population francaise atteinte de cirrhose. Materiel et methodes Pour l’etude multicentrique Cirrhose et risque de carcinome hepatocellulaire dans le grand est (CiRCE), des patients cirrhotiques avec CHC histologiquement confirme (cas) et des patients cirr…

L’obésité : un état précancéreux digestif ignoré

An explorative study to assess the association between health-related quality of life and the recommended phase II dose in a phase I trial: idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma

Objectives The objective of this study was to explore the association between health-related quality of life (HRQoL) and the recommended phase 2 dose in a phase I clinical trial according to the Time to HRQoL deterioration approach (TTD). Setting This is a phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads performed in cirrhotic patients with hepatocellular carcinoma. Patients had to complete the EORTC QLQ-C30 HRQoL questionnaire at baseline and at days 15, 30 and 60 after TACE. Participants Patients aged ≥18 years with HCC unsuitable for curative treatments were evaluated for the study (N=21). Primary and secondary outcome measurements The …

Dans l’hépatite chronique C, les délais entre diagnostic et traitement sont liés à la relation médecins-patients

Une etude epidemiologique menee en 2004 en Cote d’Or et dans le Doubs revelait que parmi 1 251 patients porteurs du VHC, un sur 4 etait traite et un sur 6 ne beneficiait d’aucune prise en charge. Une etude qualitative faite en Bourgogne en 2006-2008 visait a identifier les raisons de l’insuffisance de soins ; 25 medecins ont ete interroges sur leur confrontation a l’infection par le VHC et les difficultes de sa prise en charge, et 27 patients atteints d’hepatite chronique C sur les circonstances du depistage et du diagnostic, l’itineraire de soins, la representation et le vecu de la maladie et du traitement, les relations avec les soignants. L’etude a revele une grande variabilite dans les …

Représentations des professionnels et dépistage des hépatites B et C chez les migrants : une étude qualitative en Côte-d'Or

Les hepatites B et C sont un probleme de sante publique important en France, en particulier chez les migrants. La naissance et un sejour prolonge en pays d’endemie sont des facteurs de risque frequents, surtout pour l’hepatite B. Pourtant ces maladies restent insuffisamment depistees chez les migrants. L’objectif principal de cette etude est d’identifier les representations des professionnels de sante de Cote-d’Or du risque d’infection virale B et C des migrants pour comprendre les freins au depistage et les facteurs le favorisant. Cette etude qualitative par entretiens semi-directifs a ete menee aupres de 23 professionnels de sante et 8 travailleurs sociaux. Les professionnels de sante ont…

Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data

The incidence of hepatocellular carcinoma (HCC) is increasing in Western countries. Although several clinical factors have been identified, many individuals never develop HCC, suggesting a genetic susceptibility. However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) in the PNPLA3 gene is associated with liver damage in chronic liver diseases. Interestingly, several studies have reported that the minor rs738409[G] allele is more represented in HCC cases in chronic hepatitis C (CHC) and alcoholic liver disease (ALD). However, a significant association with HCC related to CHC has not b…

Prognostic Impact of 3-HM Concentration in Patients with Alcoholic or Viral Cirrhosis

The role of endotoxemia related to intestinal bacterial translocation in worsening liver disease is the subject of many studies, but its impact on cirrhosis mortality has not been well evaluated. In this study, 3-hydroxymyristate (3-HM) (specific lipid of lipopolysaccharides) was directly quantified by an innovative patented assay with the aim of assessing the impact on cirrhosis mortality. The 3-HM concentration was measured in 593 patients with alcoholic or viral cirrhosis in stable clinical condition. A Cox hazards regression model was used to evaluate association between 3-HM and its fractions bound or nor bound to lipoprotein and the mortality. The 3-HM concentration was increased in p…

Obesity, type 2 diabetes and risk of digestive cancer.

The frequency of obesity has been increasing worldwide for 20 years. Many epidemiological studies support a correlation between obesity and increased risk of cancer, particularly digestive cancers in both genders, and gynaecological cancer in women. Currently, about 5% of cancers could be directly related to overweight. Carcinogenesis mechanisms induced by obesity involve insulin resistance, adipokine and angiogenic factor secretions, and inflammation. Experimental and clinical evidence suggest that insulin resistance plays a major role in carcinogenesis. Insulin and non-protein banded IGF-1, whose levels are increased in type 2 diabetes, stimulate cellular growth and inhibit apoptosis. Abn…