Search

International audience; Introduction - Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. Methods - We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. Results - The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10) and higher premorbid body mass index (26.37 ± 0.16 kg/m) than controls (24.44 ± 0.18 kg/m, P = 5.77 × 10). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. Discussion - If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.

International audience; BACKGROUND and AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to eight genetic loci identified previously as associated with alcohol-related cirrhosis and three clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of three single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated for cirrhosis risk. The odds ratio (OR) and 95% confidence intervals (CI) for the extreme score quintiles (Q1-Q5) of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18;8.60) (GenomALC-1); 2.81 (2.03;3.89) (GenomALC-2); and 3.10 (2.32;4.14) (UK Biobank). Patients with diabetes and high-risk score, compared to those without diabetes and a low-risk score, had ORs increased to 14.7 (7.69;28.1) (GenomALC-1) and 17.1 (11.3;25.7) (UK Biobank). Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76±0.06 versus 0.61±0.02, p=0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on three genetic risk variants and diabetes status can provide meaningful risk stratification for cirrhosis in excess drinkers, allowing earlier prevention planning including intensive intervention. LAY SUMMARY: Excessive chronic drinking leads to liver cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. Our study has developed a genetic risk score (GRS) test that can identify patients at high risk and shows that the risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and high GRS. Risk assessment using this test has potential for early and personalised management of this disease in high-risk patients.

International audience; Background and aims - Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. Approach and results - We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. Conclusions - Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

Sugar has been shown to be a powerful substitute for drugs in preclinical studies on addiction. However, the link between sugar intake and alcohol use disorder (AUD) is poorly understood. We assessed the influence of sucrose on ethanol drinking in both nondependent (ND) and dependent (D) Long-Evans rats during acute withdrawal using the postdependent state model. Ethanol (10%-40%) and sucrose (1%-4%) solutions were offered in an operant paradigm either independently or concurrently under ratio schedules of reinforcement. We showed that D rats displayed an enhanced motivation for both 10% ethanol solution (10E) and 4% sucrose solution (4S) as compared with ND rats, and a clear preference for 4S was observed in both groups. During acute withdrawal, D rats showed a strong motivation for 30% ethanol (30E), even when adulterated with quinine, but still preferred 4S despite the fact that a high level of negative reinforcement could be expected. However, when a premix solution (30E4S) was offered concurrently with 4S, the preference for 4S was lost in D animals, which consumed as much premix as 4S, whereas ND animals displayed preference for 4S. Altogether, those results suggest that reinforcing properties of sucrose surpass those of ethanol in D rats under acute withdrawal, which indicates that sugar is a powerful substitute for ethanol. Our results suggest that craving for sugar may be increased in AUD patients during withdrawal and raise the issue of dependence transfer from alcohol to sugar.

International audience; Researchers have claimed that craving and Attentional Bias (AB) towards alcohol-related cues can be explained by a common incentive-salience mechanism. However, the exact relationship between AB and craving is a matter of debate. The aim of this study was to show that metacognitions moderate the effect of AB on craving. A sample of 38 alcohol abusers undergoing post-withdrawal treating in a hospital setting completed the visual Dot Probe Detection Task (DPDT), while both pre- and post-task measures of craving were recorded. Our results confirmed significant effects of both exposure to pictures of alcohol, and metacognitions, on craving; in particular, the interaction Metacognition * DPDT was significant. Although we initially confirmed a significant main effect of AB on craving, it became non-significant when adjusted for inter-subject variance, and metacognitions. The effect of the interaction AB * Metacognition on craving was not significant. Our findings support the hypothesis that craving and AB share variance, but the relationship appears to be spurious, and caused by confounding factors. We discuss these results with reference to the metacognitive model of addiction.

International audience; Addiction transfer from alcohol to sugar has been demonstrated in the alcohol postdependent state model in rats. To assess whether changes in sugar intake and craving can occur during alcohol withdrawal in humans we conducted a prospective, observational study in a university hospital addictions treatment center. Recruited patients had severe alcohol use disorder, were hospitalized for 7 days in the short-stay unit for alcohol withdrawal and then for 6 weeks in the rehabilitation unit. During the hospital stay, they had no access to alcohol but had full access to sweet products and beverages in a shop and vending machines located inside the hospital. Alcohol craving was assessed using a visual analogue scale on days 1, 15 and 45. Sugar craving, sweet products stored by patients in their rooms and weight were assessed on the same days. Thirty-five patients were included. Sugar craving increased in 14 patients during the hospital stay while no change was observed in the remaining 21. Significant increases in both the amounts of sweet products stored in the patients' rooms (p

Les Interventions Non Medicamenteuses (INM) sont devenues des solutions incontournables pour ameliorer la qualite de vie et la sante. Elles presentent dans certains cas un impact positif sur la duree de vie et des benefices sociaux et economiques. Leur usage augmente sans cesse. Une plateforme universitaire collaborative basee a Montpellier, la Plateforme CEPS, reflechit aux manieres de les evaluer. Cet article presente plus en detail ses activites.

International audience; Background and aims: Completely substituting e-cigarettes (EC) for combustible tobacco cigarettes reduces exposure to toxicants and carcinogens. However, a large proportion of EC users (dual users) continue to smoke conventional cigarettes. This study aimed to compare estimated nicotine intake and e-cigarette use characteristics between exclusive EC users and dual users.Design: Web-based anonymous cross-sectional survey.Setting: France.Participants: A total of 3189 adults, current users of electronic cigarettes (EC). Data collection between 4 October 2014 and 11 November 2014.Measurements: Primary outcome: estimated nicotine intake per day (mg) from participants' reports.Secondary outcomes: duration, frequency of EC use and nicotine content of e-liquids used/day. Dual use was defined as using at least one cigarette per day while also using EC.Findings: A total of 2836 respondents reported exclusive EC use and 353 reported being dual users. Backward stepwise logistic regression showed that dual users had higher estimated combined daily nicotine intake from e-liquids and cigarettes [estimate: 2.14, standard error (SE) = 0.26, adjusted odds ratio (aOR) = 8.48, 95% confidence interval (CI) = 5.11-14.09, P < 0.001], but lower daily nicotine intake from EC (estimate: -2.14, SE = 0.26, aOR = 0.12, CI = 0.07-0.196, P < 0.001) and reported fewer months of EC use (estimate: -0.31, SE = 0.14, aOR = 0.73, CI = 0.56-0.95, P = 0.022) compared with exclusive EC users.Conclusion: Dual e-cigarette users in France may have higher nicotine intake overall than exclusive e-cigarette users, but they may take in less nicotine from their e-cigarettes.

International audience; Background: The objective was to explore the role of patient sex in cognitive recovery and to identify predictive factors for non-recovery in alcohol use disorder (AUD). Methods: All patients with AUD admitted to a residential addictions treatment center were systematically assessed at admission and after 6 weeks of abstinence in a controlled environment. The inclusion criteria were that patients were admitted for AUD with baseline alcohol-related cognitive impairment (baseline total Montreal Cognitive Assessment (MoCA) score \textless 26) and reassessed at 6 weeks (n = 395). A logistic regression model was built to determine the influence of sex on recovery status (MoCA \textless or >= 26) taking into account the interaction effect of sex with alcohol consumption on cognitive function. Results: The mean age was 50.10 years (SD = 9.79), and 27.41% were women. At baseline, the mean MoCA scores were 21.36 (SD = 3.04). Participants who did not achieve recovery (59.3% of women vs 53.8% of men) had lower total MoCA scores at baseline. The 2 factors that was significantly and independently associated with non-recovery and with a non-zero coefficient was being a woman and initial MoCA score (respective adjusted odds ratios (AOR) = 1.5 and 0.96, p-values \textless 0.05). Conclusions: These results could influence the time required in a controlled environment to maintain abstinence and the duration of in-care for women.

International audience; OBJECTIVE:The aim of this study was to evaluate the prevalence and the kind of psychoactive substances consumed by people with obesity.METHODS:Patients were included at their first visit for bariatric surgery. Socio-demographic characteristics, anxiety, depressive disorders and psychoactive substance consumption were assessed. The prevalence of psychoactive substance consumption was compared to that of the general population reported by the French National Institute of Prevention and Health Education.RESULTS:One hundred (100) patients were consecutively recruited: 60 women (mean age 41 ± 14 years) and 40 men (mean age 46 ± 13 years). Sixty-seven percent of subjects consumed alcohol. Consumption rates of cannabis (21% vs. 10%), cocaine (7.0% vs. 0.8%) and amphetamine (6.0% vs. 0.3%) were significantly (p < .0001) higher in people with obesity than in the general population.CONCLUSIONS:People with obesity have an excess risk of amphetamine, cocaine and cannabis consumption. This consumption may increase the risk of cardiovascular and psychiatric morbidity and should therefore be detected before surgery.

Introduction Screening of cognitive impairment is a major challenge in alcoholics seeking treatment, since cognitive dysfunction may impair the overall efficacy of rehabilitation programs and consequently increase relapse rate. We compared the performance of two screening tools: the MoCA (Montreal Cognitive Assessment), which is widely used in patients with neurological diseases and already used in patients with alcohol use disorder (AUD), and the BEARNI (Brief Evaluation of Alcohol-Related Neuropsychological Impairments), a recent test specifically developed for the alcoholic population. Methods We compared the sensitivity and specificity of the MoCA and the BEARNI in a sample of AUD patients with and without cognitive impairment assessed by a battery of neuropsychological tests. Results Ninety patients were included. There were 67 men and 23 women aged 48.9 ± 9.6 years. According to the neuropsychological tests, 51.1% of patients had no cognitive impairment, while it was mild or moderate to severe in 31.1 and 17.8%, respectively. The BEARNI sensitivity was extremely high (1.0), since all patients with cognitive impairment were identified, but its specificity was very low (0.04). The MoCA had a lower sensitivity (0.79) than the BEARNI, but its specificity was significantly better (0.65). A detailed analysis of the BEARNI scores showed a discrepancy between the qualitative and quantitative interpretation of the test which could, at least in part, explain its low specificity. Conclusion Both the MoCA and the BEARNI are screening tools which identified alcoholic patients with cognitive impairment. However, in routine use, the MoCA appeared to be more appropriate given the low specificity of the BEARNI.

International audience; BACKGROUND : The Montreal Cognitive Assessment (MoCA) score is a convenient and promising tool for estimating alcoholic patients' global cognitive functioning, a major challenge for all specialized alcohol treatment centers. However, whether or not the score should be corrected for education level and whether the proposed cutoff is relevant in patients with alcohol use disorders (AUD) should be determined.METHODS : We compared the MoCA scores in patients hospitalized for AUD with and without cognitive impairment assessed by a battery of neuropsychological (NP) tests. Sensitivity, specificity, and cutoff of the MoCA score were analyzed using receiver operating characteristic curve analysis.RESULTS : Thirty-one patients with and 25 without cognitive impairment were included in the study. There were 40 men and 16 women, with a mean age of 49.5 years. The mean uncorrected MoCA score was 23.1 ± 3.3 in those with and 27.0 ± 1.9 in those without cognitive impairment. NP tests were significantly correlated with the MoCA score. Uncorrected MoCA scores identified more than 80% of the patients with a cutoff score equal to 26, to obtain similar accuracy with the corrected score required using a cutoff score equal to 27.CONCLUSIONS : Our results confirm that the MoCA test is a convenient and reliable screening tool to measure cognition defects in alcoholic patients. As using the 1-point education adjustment increases the cutoff score by 1 point, it is suggested to use the noncorrected score and the usual cutoff, that is, 26. Being easy to administer and only moderately time-consuming, the MoCA score should be used extensively in addiction treatment centers.

Author(s): Whitfield, John B; Rahman, Khairunnessa; Haber, Paul S; Day, Christopher P; Masson, Steven; Daly, Ann K; Cordell, Heather J; Mueller, Sebastian; Seitz, Helmut K; Liangpunsakul, Suthat; Westerhold, Chi; Liang, Tiebing; Lumeng, Lawrence; Foroud, Tatiana; Nalpas, Bertrand; Mathurin, Philippe; Stickel, Felix; Soyka, Michael; Botwin, Gregory J; Morgan, Timothy R; Seth, Devanshi; GenomALC Consortium | Abstract: BackgroundThe risk of alcohol-related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS).MethodsThe GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high-risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected.ResultsWe have successfully recruited 859 participants including 538 matched case-control samples as of September 2014, using study-specific inclusion-exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95% confidence interval 1.31 to 4.87, pn=n0.0055).ConclusionsRecruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.

ObjectiveThe natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. Design We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR.ResultsAge at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. ConclusionsMost factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable. Refereed/Peer-reviewed

International audience; BACKGROUND:Alcohol relapses after liver transplantation (LT) constitute a critical issue. Because there is no widely accepted definition of LT, its prevalence varies from 7 to 95% across studies. Only a severe relapse, the frequency of which is estimated to be 11 to 26%, decreases life expectancy after 5 years of LT and requires specific care. To improve the early identification of alcohol consumption among transplanted patients, liver transplant teams may be helped by input from an addiction team. Nevertheless, added benefit of involvement by addiction specialists in treating posttransplant patients has not been demonstrated. Thus, the aim of this study was to compare the evaluation of the alcohol consumption after LT performed routinely during the transplant consultation or obtained from a specific addiction consultation.METHODS:This was a prospective single-site study. Patients were seen consecutively by their hepatologist and by an addiction specialist, and they completed the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Thus, the patient's alcohol status was assessed using 3 different sources of information: the hepatologist's interview, the AUDIT-C score, and the addiction specialist visit.RESULTS:One hundred forty-one patients were consecutively evaluated. Alcohol consumption was identified by the hepatologist in 31 patients (21.9%), in 52 (36.8%) using the AUDIT-C questionnaire, and in 58 (41.1%) by the addiction specialist. The 31 patients concerned reported an average of 6.5 alcohol units/wk to the transplant physician, a number which was significantly greater (p = 0.001) by 8.6 units/wk when they were interviewed by the addiction specialist.CONCLUSIONS:This study highlights the clinical utility of a systematic addiction consultation among liver transplant patients, irrespective of the reason for transplantation.

Alcoholic liver disease (ALD) causes more than 5000 deaths per year in France. Most of those deaths could be prevented by an early diagnosis, which would give the patients the opportunity to modify their alcohol consumption while liver lesions are still reversible. Hepatic histology is the main parameter that predicts morbidity and mortality in patients with ALD. Non-invasive methods such as biomarker tests (e.g. FibroTest(®) or FibroMetre A(®)) or hepatic elastography (FibroScan(®)) may allow diagnosing alcohol-induced liver lesion without systematic biopsy. Despite promising preliminary results, those methods are not validated yet in ALD. A validation of non-invasive methods for ALD could allow a large screening of the severe forms of this pathology.

We report a new strategy based on scientific education for sensitizing teenagers to the addiction-related harms. This strategy is diverted from a program called “Apprentis Chercheurs”. Pairs of young adolescents are welcome in research laboratories working on addiction all along the school year. They are fully integrated in the research team and directly participate to the experiments under the supervision of a senior researcher. At the end of the school year, they orally communicate their results to other students of their schools, their teachers, their parents and the research team in a peer-to-peer approach during a scientific conference organized within every participant research center.

Background: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment. Method: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later. Results: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%). Conclusion: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.

Aim : Optimal management of hepatitis C virus (HCV) infection is controversial in heavy drinkers. We compared the management of HCV infection of heavy drinkers with that of patients without a history of alcohol abuse. Methods : In a retrospective case–control study, 69 HCV-infected heavy drinkers [daily alcohol consumption at referral above 60 g/day, hereafter ‘alcohol group’] were compared with matched HCV-infected patients with low alcohol consumption (

This study aims to evaluate the effectiveness of a web-based intervention to reduce alcohol consumption among hazardous drinkers. A two-group parallel randomized controlled trial was conducted among adults identified as hazardous drinkers according to the Alcohol Use Disorders Identification Test. The intervention delivers personalized normative feedback and some general information about alcohol. Participants can review their motivations and fears regarding reducing their alcohol intake, set individual goals and monitor their progress via a consumption diary and other tools. Within the control group, participants were provided with the same diary but could not access other services from the program. The primary outcome measure was the absolute difference in weekly alcohol intake (WAI) between baseline and 6-week follow-up. Secondary outcome measures included: relative difference in WAI; difference in excessive drinking and significant WAI reduction (decrease of 10% or more in WAI). One thousand one hundred and forty-seven people participated in the trial and 339 subjects completed it. Relative to the control group, participants in the intervention group reported a significantly greater mean absolute reduction in WAI (-3.3 versus -1.2, P = 0.03). Secondary outcomes also presented significant effects. This trial provides preliminary support to the effectiveness of this program in helping hazardous drinkers reduce their drinking, provided it is completely and regularly used.

Background. Cognitive dysfunction is a common feature in alcohol use disorders. Its persistence following alcohol detoxification may impair quality of life and increase the risk of relapse. We analyzed cognitive impairment changes using the Montreal Cognitive Assessment (MoCA) score in a large sample of alcohol-dependent inpatients hospitalized for at least 4 weeks. Method. This was an observational longitudinal survey. Inclusion criteria were alcohol dependence (DSM-IV) and alcohol abstinence for at least one week. The MoCA test was administered on admission and at discharge. Results. 236 patients were included. The mean MoCA score significantly increased from 22.1±3.7 on admission to 25.11±3.12 at discharge. The corresponding effect-size of improvement was high, 1.1 [95% CI 1.0–1.2]. The degree of improvement was inversely correlated with the baseline MoCA score. The rate of high and normal, that is, >26, MoCA values increased from 15.8% on admission to 53.8% at discharge. MoCA score improvement was not correlated with the total length of abstinence prior to admission. Conclusion. The MoCA score seems to be a useful tool for measuring changes in cognitive performance in alcohol-dependent patients. A significant improvement in cognitive function was observed whatever the degree of impairment on admission and even after a long abstinence period.

Article disponible en ligne à l'adresse : http://www.scirp.org/journal/psych; International audience; We performed a community research program in order to analyze the evolution of interpersonal values following alcohol withdrawal in alcoholics attending to a self-help group. The Gordon ques-tionnaire on interpersonal values was administered every 3 months during one year to 145 indi-viduals having recently stopped drinking. At baseline, scores of 5 interpersonal categories (de-pendence, conformism, consideration, independence, kindness) were in the medium interval of usual values while that of command category was low, specifically in men. Values of conformism and independence increased according to time while those of dependence and consideration de-creased but the differences were significant only in those who remained abstinent all along the observation period. In those who relapsed, there were no modifications; however, sharing these values might have allowed these subjects to be less isolated. We will describe in details the nature of these evolutions.

SUMMARY. A new hepatitis B virus (HBV) protein, hepatitis B splice-generated protein (HBSP), has been detected in liver biopsy specimens from patients with chronic active hepatitis. The aim of this study was to characterize the phenotype and functions of peripheral HBSP-specific T cells and to determine whether these T-cell responses may be implicated in liver damage or viral control. Two groups of patients were studied: HBV-infected patients with chronic active hepatitis and HBV-infected patients who were inactive carriers of hepatitis B surface antigen. HBSP-specific T-cell responses were analysed ex vivo and after in vitro stimulation of peripheral blood mononuclear cells. Soluble cytokines and chemokines were analysed in sera and in cell culture supernatants. Few HBSP- or capsid-specific T-cell responses were detected in patients with chronic active hepatitis whereas frequency of HBV-specific T cells was significantly higher in inactive carrier patients. HBSP activated CD8+ and CD4+ T cells that recognized multiple epitopes and secreted inflammatory cytokines. The IL-12 level was significantly lower in sera from asymptomatic carrier patients compared to patients with chronic active hepatitis. IL-12 and IP-10 levels in the sera were significantly and independently correlated with both alanine amino transferase and HBV DNA levels. Our results show that the HBSP protein activates cellular immune responses in HBV-infected patients but has probably no prominent role in liver damage. The pattern of cytokines and chemokines in sera was linked to HBV viral load and was consistent with the level of inflammation during chronic hepatitis.

Background: Measurement of liver stiffness (LS) using real-time elastography appears as a promising tool to evaluate the severity of chronic liver diseases. Previous studies in patients with alcoholic liver disease have suggested that fibrosis was the only histological parameter to influence LS. To challenge this hypothesis, we have prospectively tested the short-term impact of alcohol withdrawal on LS value. Methods: Patients hospitalized for alcohol withdrawal in our Liver and Addiction Unit between 2007 and 2010 had an LS determination at entry (D0) and 7 days after alcohol withdrawal (D7). LS value was given as the median of 10 measurements performed with a FibroScan® device. For a given patient, variation of LS was considered as significant when the comparison of the 10 measurements at D0 and at D7 yielded a p-value under 0.05 (Wilcoxon test). Results: One hundred and thirty-seven patients were included in the study (median alcohol consumption: 150 g/d; hepatitis C: n = 21 [15.6%]). Considering all patients, median LS value decreased from 7.2 to 6.1 kPa between D0 and D7 (p = 0.00001, paired Wilcoxon test). LS decreased significantly in 62 patients (45.3%), and there was a reduction in the estimated stage of fibrosis in 32 (23.3%). LS increased significantly in 16 patients (11.7%). Subgroup analyses revealed that the decrease in LS was still significant in patients with or without hepatitis C infection, and aspartate transaminase level below or above 100 UI/l. Conclusions: LS decreases significantly in nearly half of heavy drinkers after only 7 days of abstinence. This result strongly suggests that nonfibrotic lesions (such as the presence of alcoholic hepatitis) may influence LS. From a practical point of view, it also shows that variation of alcohol consumption must be taken into account for the interpretation of LS value.

Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.

International audience; Supersonic shear imaging (SSI) has recently been demonstrated to be a repeatable and reproducible transient bidimensional elastography technique. We report a prospective clinical evaluation of the performances of SSI for liver fibrosis evaluation in 113 patients with hepatitis C virus (HCV) and a comparison with FibroScan (FS). Liver elasticity values using SSI and FS ranged from 4.50 kPa to 33.96 kPa and from 2.60 kPa to 46.50 kPa, respectively. Analysis of variance (ANOVA) shows a good agreement between fibrosis staging and elasticity assessment using SSI and FS (p , 10 25). The areas under receiver operating characteristic (ROC) curves for elasticity values assessed from SSI were 0.948, 0.962 and 0.968 for patients with predicted fibrosis levels F $ 2, F $ 3 and F 5 4, respectively. These values are compared with FS area under the receiver operating characteristic curve (AUROC) of 0.846, 0.857 and 0.940, respectively. This comparison between ROC curves is particularly significant for mild and intermediate fibrosis levels. SSI appears to be a fast, simple and reliable method for noninvasive liver fibrosis evaluation.

Background Only a minority of patients with chronic hepatitis C virus (HCV) infection develops severe liver fibrosis, a process that may be controlled by human genetic factors. Objective To investigate the role of 384 single nucleotide polymorphisms (SNPs) located in 36 candidate genes related to the fibrogenesis/fibrolysis process. Methods Patients with chronic HCV infection were gathered from two French cohorts (prospectively and retrospectively). The overall sample consisted of 393 HCV-infected subjects without known risk factors for fibrosis progression, including 134 patients with severe liver fibrosis and 259 without severe fibrosis. Results Only two SNPs in strong linkage disequilibrium (LD) in the interferon γ receptor 2 gene ( IFNGR2 ) were significantly associated with liver fibrosis in both the prospective and the retrospective samples. The strongest association (p=8×10 −5 ) was observed with the G/A SNP rs9976971 with an OR of severe fibrosis for AA versus AG or GG subjects at 2.95 (95% CI 1.70 to 5.11). This effect was higher (p=9×10 −7 ) when taking into account the time of follow-up, and the hazard ratio of progression towards severe fibrosis for AA patients was 2.62 (1.76 to 3.91). Refined sequencing and analysis of the IFNGR2 region identified two additional variants in strong LD with rs9976971. No haplotypes derived from this cluster of four variants provided stronger evidence for association than rs9976971 alone. Conclusions This identification of a cluster of four IFNGR2 variants strongly associated with fibrosis progression in chronic HCV infection underlines the role of IFNγ in the development of liver fibrosis that may pave the way for new treatments.

Background. Defective hepatitis B virus (HBV) particles, generated from singly spliced HBV RNA, have been detected in chronic carriers of HBV. The present study was designed to quantify the expression of defective HBV (dHBV) and wild-type HBV (wtHBV) genomes in the serum of patients with HBV infection and its relation to the severity of liver disease. Methods. HBV and dHBV loads were determined by quantitative polymerase chain reaction in the serum of 89 untreatedHBV-infectedpatients(31coinfectedwithhumanimmunodeficiencyvirus[HIV]type1)withliverdisease of different stages. The ratio of dHBV DNA to total (wtHBV plus dHBV) HBV DNA (dHBV/HBV ratio) was used to express data independently of the level of viral replication. Results. DespiteaglobalcorrelationbetweendHBVandwtHBVload,thedHBV/HBVratiorangedfrom0.001% to 69%. The variation in dHBV/HBV ratio was independent of HIV coinfection, HBV genotype, and precore mutations. The mean dHBV/HBV ratio was higher in patients with severe liver necrosis and fibrosis. Conclusions. OurdataindicatethatanelevateddHBV/HBVratioisassociatedwithlivernecroinflammationand fibrosis disease, suggesting a regulation of dHBV expression according to the severity of the liver disease. The dHBV/ HBV ratio may help to better define liver disease stage during HBV infection. Persistent human hepatitis B virus (HBV) infection is a major public health problem. The major complications of chronic HBV infection are the development of liver cirrhosis and hepatocellular carcinoma (HCC) [1‐3]. Evidence indicating a direct involvement of HBV in this process is now available [3]; indeed, recent data have demonstrated that serum HBV DNA levels are strong predictorsoftheriskofHCC,independentofhepatitisB e antigen (HBeAg) expression, serum alanine amino

Background: Liver biopsy indication for the evaluation of alcoholic liver disease is controversial. Our aim was to investigate the influence of the biopsy on the patients’ motivation for abstinence. Methods: We retrospectively analysed, in a population of 324 patients hospitalized for alcohol withdrawal, the impact of liver biopsy on the following clinical outcomes: rapid loss to follow-up (immediately after hospital discharge), early relapse ( 12 months). The biopsy was performed in 136 patients who had liver enzymes perturbations. Hepatic lesions were graded as mild (isolated steatosis and/or non-bridging fibrosis), moderate (bridging fibrosis and/or moderate alcoholic hepatitis) or severe (cirrhosis and/or marked alcoholic hepatitis) in 66 (48%), 41 (30%) and 29 (21%) cases, respectively. Results: In univariate analysis, patients who had a liver biopsy were less likely to be rapidly lost to follow-up (12% versus 27%, P = 0.003) but had a lower rate of long-term abstinence (20% versus 34%, P = 0.025). In multivariate analysis, age was the only factor significantly associated with clinical outcome: older patients had higher rate of long-term abstinence (OR = 1.041; P = 0.010). Among patients who had a biopsy, those with severe hepatic lesions had a lower rate of rapid relapse than those with moderate or mild lesions (32% versus 68% and 56%, P = 0.018) but the rate of long-term abstinence was similar in the three groups. Conclusion: This observational study does not support the notion that liver biopsy has a significant influence on the maintenance of alcohol abstinence in patients with alcoholic liver disease.

The clone C2 derived from a rat hepatoma cell line was used to investigate the mechanism of the induction of gamma-glutamyltransferase by ethanol. gamma-glutamyltransferase activity was detected in the C2 cell (1.4 mU per mg protein), and its kinetic properties were similar to normal rat liver gamma-glutamyltransferase. Ethanol provoked a dose- and time-dependent increase in gamma-glutamyltransferase activity, the maximum (2- to 3-fold) occurring 48 hr after the addition of ethanol (180 mM). In contrast, the activity of five other enzymes tested were not markedly modified by ethanol. Propanol was more potent than ethanol in inducing gamma-glutamyltransferase (5-fold stimulation), whereas methanol had no effect. The release of the enzyme in the medium was increased by ethanol and propanol. Several observations argue in favor of an increase in the biosynthesis of gamma-glutamyltransferase after ethanol addition: (i) ethanol increased the maximal velocity of the enzyme and did not modify the affinity for its substrates. It did not alter gamma-glutamyltransferase subcellular distribution; (ii) ethanol had no immediate effect when added directly to the assay mixture; (iii) the lag period and the time course of the increase in gamma-glutamyltransferase activity were those expected for an induction process; (iv) the increase in gamma-glutamyltransferase activity was prevented by cycloheximide and actinomycin D suggesting that ethanol acted at the transcriptional level. The effect of ethanol was not mimicked by acetaldehyde. In conclusion, we have demonstrated that ethanol increases the biosynthesis of gamma-glutamyltransferase in a rat hepatoma cell line which provides a new in vitro system.

To optimize the management of patients with chronic hepatitis C virus (HCV) infection, noninvasive tests to determine the degree of hepatic fibrosis have been developed. The aims of this study were (1) to validate a simple, inexpensive, noninvasive test called FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age, in a series of 847 liver biopsies performed in HCV-monoinfected patients; and (2) to compare the results of 780 FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected patients. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93), respectively. An FIB-4 index1.45 had a negative predictive value of 94.7% to exclude severe fibrosis with a sensitivity of 74.3%. An FIB-4 index higher than 3.25 had a positive predictive value to confirm the existence of a significant fibrosis (F3-F4) of 82.1% with a specificity of 98.2%. Using these ranges, 72.8% of the 847 liver biopsies were correctly classified. The FIB-4 index was strongly correlated to the FibroTest results for a score1.45 or3.25 (kappa = 0.561, P0.01). A FIB-4 value1.45 or3.25 (64.6% of the cases) was concordant with FibroTest results in 92.1% and 76%, respectively.For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and inexpensive method for assessing liver fibrosis and proved to be concordant with FibroTest results.

Objective No efficient medical treatment is available for severe acute hepatitis (SAH) except N-acetylcysteine for acetaminophen-induced acute liver failure. The human C-type lectin Reg3α, referred to as ALF-5755, improved survival in an animal model of acute liver failure and was well tolerated in a phase 1 trial in humans. We performed a phase 2a trial of ALF5755 in non-acetaminophen induced SAH. Design double-blind, randomized, placebo-controlled study. The primary end-point was the improvement in the coagulation protein synthesis assessed by the change of Prothrombin (PR) during the 72 hours following treatment initiation calculated as PRH0 minus PRH72 divided by 72 (PR slope H0H72). Intention to treat (ITT) and per-protocol (PP) analysis of the entire group and the Hepatitis B virus (HBV)/AIH (auto-immune hepatitis) sub-group were done separately. Results 57 patients were included. Twenty-eight received ALF-5755, 29 the placebo. Etiologies were: Hepatitis A (n = 10), HBV (n = 13), AIH (n = 9), drug-induced (n = 8), other (n = 17). On the whole group, nor the PR slope H0H72 (0.18±0.31 vs 0.25±0.32), nor the transplant-free survival rate at day 21 (75 vs 86%) differed between groups. Conversely, in the HBV-AIH subgroup, in which ALF was more severe, PR slope H0-H72 was higher in the ALF-5755 arm, the difference being significant in PP analysis (0.048±0.066 vs -0.040±0.099, p = 0.04); the median length of hospitalization was lower in the ALF-5755 group (8 vs 14 days, p = 0.02). Conclusion ALF-5755 was not efficient in a ITT analysis performed on the whole sample; however it led to a significant, although moderate, clinical benefit in a PP analysis of the sub-group of patients with HBV or AIH related SAH. As HBV is the major cause of SAH in Asia and Africa and AIH a growing cause, this study emphasizes the need to pursuit the evaluation of this novel medical treatment of SAH. Trial Registration ClinicalTrials.gov NCT01318525

International audience; BACKGROUND:Alcoholism is known to be associated with cognitive deficits mainly concerning visuospatial capacity, executive function, memory, and attention. These impairments may affect treatment efficacy which should therefore be adapted. We evaluated the potential utility of the Montreal Cognitive Assessment (MoCA) to evaluate cognitive impairment in a large series of alcoholic patients hospitalized for withdrawal and rehabilitation.METHODS:Consecutive recruitment during a time period of patients admitted to an addiction treatment unit of a teaching hospital. Administration of the MoCA test on admission by trained staff members.RESULTS:A total of 166 patients aged 49.9 ± 9.2 years were included. Mean duration of administration was 20 minutes. The mean MoCA score was 23.5 ± 3.5 and 68.1% had an impaired value (12 years) significantly increased the likelihood of having a high MoCA score.CONCLUSIONS:Owing to their severity and frequency, screening for cognitive deficits is necessary in alcoholics during rehabilitation. MoCA is an appropriate tool for this purpose.

An accurate diagnosis of hepatitis C virus (HCV)-related liver lesions is mandatory in dialysis patients and kidney recipients to better define the treatment of and contraindications to kidney transplantation. The aim of this study was to assess the diagnostic accuracy of the fibrotest (a noninvasive method to assess liver fibrosis in HCV on a scale from 0 to 1) in hemodialysis and renal transplant patients infected by chronic HCV.In all, 110 patients with biopsy-proven HCV (60 renal transplant recipients and 50 hemodialysis patients), determined using the METAVIR scoring system, were studied.Forty-six percent of patients had fibrosisor =F2. A positive predictive value of a score0.6 for the presence of significant fibrosis by comparison with liver biopsy was 71%, and an negative predictive value of0.2 for excluding significant fibrosis was 77%, respectively. The areas under the ROC curves for the diagnosis of significant fibrosis were 0.66, 0.47, and 0.71 in the global population, hemodialysis patients, and renal transplant patients, respectively. In all, 75% of patients were correctly classified using the fibrotest. If biopsy was restricted to scores in the intermediate range (0.6 and0.2), the index could reduce the indication for biopsy by 47%. The results did not differ significantly in hemodialysis and renal transplant patients.The fibrotest has a diagnostic value in hemodialysis and renal transplant patients which is similar to that reported in the general population (75%) and its use could avoid 32% of liver biopsies if it were interpreted in detail in nephrology patients.

Aim To evaluate the benefits of haematopoietic growth factors (HGFs) during the treatment of chronic hepatitis C virus (HCV) infection with severe haematotoxicity. Methods This was a 1-year retrospective study of HCV-positive patients receiving pegylated interferon and ribavirin. Patients received different HGFs, depending on certain criteria: they received erythropoietin (EPO) when their haemoglobin (Hb) levels were less than 10 g/dl and granulocyte colony-stimulating factor (G-CSF) when their neutrophil count was less than 750 cells/mm3. Haematological data, adherence and virological response were analysed and compared according to HGF use. Results In total, 132 patients were studied and 31 (23.5%) required HGF. Under multivariate analysis, baseline Hb levels of less than 13g/dl or a drop in Hb levels of over 2% per week predicted severe anaemia, and a base-line neutrophil count under 2900/mm3 predicted severe neutropaenia. HGF administration restored Hb values and the neutrophil count to above 10 g/dl and 1500 cells/mm3, respectively, in all 31 patients. Adherence to antiviral treatment was achieved in 25% of patients versus 58% of controls without severe haematotoxicity. The primary and sustained virological response did not differ statistically between HGF support and the control group (61% versus 57% and 32% versus 39%, respectively). Conclusion HGF administration counteracts the severe haematological adverse effects which occur during antiviral therapy and maintains the rate of sustained response.

AIMS: Although the prevalence of alcohol problems amongst detainees is suspected to be high, often only more flagrant problems are detected, restricting the possibilities for intervention in alcohol misuse and reducing opportunities for preventive efforts. This study examined the re-test reliability of AUDIT (the Alcohol Use Disorder Identification Test) in screening prisoners METHODS: AUDIT was administered for the first time on the day of entry to prison and again about 15 days later. The results were analysed according to two AUDIT thresholds: a score of 8 or higher and 12 or higher. RESULTS: Of 75 consecutive entrants tested, 47 male prisoners completed the study. At the first administration, 19.1% of these 47 men met criteria for a probable alcohol problem but this percentage rose to 59.6% on the second occasion (P = 0.0001). The proportion of subjects with a score 12 or higher (probably dependent) was 10.6% the first time versus 42.6% the second time (P = 0.0001). In the 19 who scored positive at the second administration only, changes in answers to the 10 items were coherent with a total score growing from 3.0 to 18.1 (P = 0.0001). No prisoner had a lower AUDIT score on the second administration. As alcohol problems are not routinely considered during the medical and biological examination at entry, no confirmation of the AUDIT results could be obtained, although those obtained at the second administration fitted well with the prevalence rates in previous reports. CONCLUSIONS: AUDIT, for the purpose of giving a prevalence estimate or to enter appropriate prisoners into more detailed assessment or interventions, should not be conducted immediately at entry, but some weeks later.

The aim of this retrospective study was to determine the potential reversibility of hepatitis C virus (HCV) cirrhosis with the combined antifibrotic effects of interferon-alpha and the increasing frequency of sustained virologic response. Sixty-four HCV-cirrhotic immunocompetent patients who underwent antiviral therapies (interferon-alpha with or without ribavirin) and pretreatment and posttreatment liver biopsies were included (group 1). Resolution of cirrhosis was defined as a decrease in the fibrosis score from 4 to 2 or less by the Metavir score after blinded analysis by 2 independent pathologists. An additional group of 4 HCV-infected dialysis patients (group 2) who had received antiviral treatment, among whom 3 underwent a combined renal and liver transplantation allowing the analysis of the whole liver, was also studied. In 5 (all stage Child A) of the 64 cirrhotic patients (7.8%), the final biopsy showed only F2 to portal and periportal fibrosis with rare fibrous septa without nodule formation. Four of these 5 were complete sustained responders (negative PCR and normal ALT), and 1 was a relapser. In group 2, reversibility of cirrhosis was observed in 3 of the 4 patients and was clearly shown in 2 patients by the analysis of the whole-liver examination at the time of the hepatectomy preceding the transplantation. In conclusion, long-lasting suppression of the necroinflammatory activity of liver disease and/or antifibrogenetic effects of interferon-alpha may allow regression of cirrhosis.

Background/Aims : Alcohol consumption accelerates the appearance of liver fibrosis and hepatocellular carcinoma in patients with chronic hepatitis C virus (HCV) infection, but the mechanisms of these interactions are unknown. We therefore investigated the effects of chronic ethanol consumption in HCV core protein-expressing transgenic mice. Methods : Ethanol was progressively added (up to 20%) to the drinking water that was given ad libidum. Results : In vivo fatty acid oxidation was not inhibited by ethanol consumption and/or HCV core expression. Both chronic ethanol consumption and HCV core expression decreased hepatic lipoprotein secretion and caused steatosis, but had no additive effects on lipoprotein secretion or steatosis. However, chronic ethanol consumption and HCV core protein additively increased lipid peroxidation and acted synergistically to increase the hepatic expression of transforming growth factor-β (TGF-β) and, to a less extent, tumor necrosis factor-α (TNF-α). Conclusions : HCV core protein expression and chronic alcohol consumption have no effects on in vivo fatty acid oxidation and do not additively impair hepatic lipoprotein secretion, but additively increase hepatic lipid peroxidation and synergistically increase hepatic TNF-α and TGF-β expression. These effects may be involved in the activation of fibrogenesis and the development of hepatocellular carcinoma in patients cumulating alcohol abuse and HCV infection.

Background/Aims : We have previously demonstrated the in vivo expression of a new spliced hepatitis B virus (HBV) protein (HBSP) encoded by a singly spliced pregenomic RNA. The present study was designed to evaluate the impact of HBSP expression on the clinical status and liver pathology of HBV infection. Methods : Sera from 125 chronic HBV carriers were tested for the presence of HBSP antibodies by an indirect enzyme-linked immunosorbent assay test. The severity of liver damage was evaluated using the Knodell score. Results : Anti-HBSP antibody prevalence in HBV chronic carriers was 46%. We highlighted the concomitant expression of HBSP protein and anti-HBSP antibody. An association between anti-HBSP antibody detection and serum markers of HBV replication was demonstrated. With respect to HBV-related liver disease, an association was only observed with the severity of fibrosis. Furthermore, an elevation of secreted tumor necrosis factor α (TNF α ), but not of soluble TNF α receptor 75, was observed in anti-HBSP-antibody-positive patients. Multivariate analysis showed that anti-HBSP antibody detection was independently associated with viral replication, severity of fibrosis and elevated TNF α secretion. Conclusions : Our data suggest the hypothesis that HBSP might play a role in the natural history of HBV infection and may be involved in the pathogenesis and/or persistence of HBV infection.

Article en libre accès : http://file.scirp.org/Html/5-6901050_44430.htm; International audience; Many studies have examined the risk factors for relapse in alcohol-dependent patients within the first year of treatment, and have generally focused on two personality dimensions: emotional instability and difficulty in establishing relationships. In this study, we examine if these weaknesses remain in prolonged alcohol abstinence. To do so, we administer the NEO PI-R to two groups of subjects. Group 1, Inactive Drinkers (ID), consists of 51 patients with at least two years of abstinence (average length of abstinence for this group is 6.2 years); Group 2, Recently Detoxified Drinkers (RDD), comprises 93 patients who have recently ceased consuming alcohol. Based on NEO PI-R scores, our results evidence that inactive drinkers experience significant reduction in emotional instability and improvement in relationships to others. We further observe that, with long-term abstinence, these personality dimensions normalize, ceasing to be risk factors for relapse. Additionally, we find that this long-term amelioration of traits altered by alcohol amounts to an improved behavioral adaptation to life events rather than an actual change in personality.

To analyze the spontaneous pathologic progression of chronic hepatitis C, we analyzed the histopathologic semiquantitative scores (Metavir and Knodell) of sequential liver biopsies performed in untreated hepatitis C virus (HCV)-infected patients. Subjects included 35 men and 41 women, with a mean age of 41 +/- 12 years, a duration of HCV infection of 11 +/- 5 years, and an interval between liver biopsies of 3.7 +/- 2.5 years. Results obtained using the Knodell score and the Metavir score were similar. At the first biopsy, 78.9% of patients had a low activity score (A0-A1) and 82.9% had a low fibrosis score (F0-F2). At the second biopsy, the activity decreased in 9.2%, was unchanged in 72.4%, and increased in 18.5%. An increase in activity was more frequently observed in patients infected with genotype 1 (28.9%) than with others (7.7%; P =.04); the yearly progression of activity was significantly higher in patients with a low rather than high initial activity score (0.11 v -0.02; P.01). An increase in fibrosis was noted in 13.3% of those with a low and 43.8% of those with a high initial activity score (P.01), with a highest rate of yearly fibrosis progression (0.12 U). In multivariate analysis, only a high activity score was significantly associated with an increased risk of fibrosis progression (relative risk, 25.5; 95% confidence interval, 2.7 to 238; P =.004). Spontaneous chronic hepatitis C evolution is worsening in only 20% of patients. Fibrosis progression is significantly associated with the necroinflammatory activity suggesting that this factor should be regarded as a major clue for deciding therapy.

The prevalence and pathogenicity of TT virus, recently identified in patients with non A-non G post-transfusional hepatitis, are questioned.We investigated the impact of this new viral infection in a large series of patients with non A-non G, cryptogenic, non-viral and viral-related, acute and chronic liver diseases (n=577) and blood donors (n=300). TTV DNA was detected in serum by hemi-nested polymerase chain reaction. Phylogenetic analysis was performed in 13 isolates.TTV DNA was detected in 6/25 and 15/127 patients with cryptogenic non A-non G acute and chronic liver disease, respectively. TTV DNA positive subjects with post-transfusional acute hepatitis scored negative before transfusion. TTV prevalence was increased in patients with cryptogenic non A-non G acute and chronic liver disease compared to blood donors (6/300; p0.001) and non-viral-related chronic liver diseases (6/137; p0.05). TTV/HBV coinfection was frequently identified (35/147), but this was not the case for HCV-infected subjects (4/77). Transaminase activity or liver histological score was not significantly increased among TTV positive, HBV infected or non A-non G patients. The HBV infection and Mediterranean origin were the risk factors associated with TTV infection. The majority of analysed sequences clustered in genotype 1 (8=1b; 3=1a). Two isolates showed homology to genotype 2.These results support the view that TTV is a widely spread infectious agent with a weak pathogenicity. It raises the possibility, however, that TTV might be implicated in a few cases of acute and chronic non A-non G hepatitis. TTV-DNA-analysed sequences are related to genotypes 1 and 2 described in Europe.