A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry.

BACKGROUND: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis. METHODS: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239). RESULTS: A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis. CONCLUSIONS: PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.

Predictive Value of Circulating Tumor Cells Detected by ISET® in Patients with Non-Metastatic Prostate Cancer Undergoing Radical Prostatectomy.

There is an unmet need for reliable biomarkers to predict prostate cancer recurrence after prostatectomy in order to better guide the choice of surgical treatment. We have evaluated the predictive value of the preoperative detection of Circulating Tumor Cells (CTC) for prostate cancer recurrence after surgery. A cohort of 108 patients with non-metastatic prostate adenocarcinoma undergoing radical prostatectomy was tested for the presence of CTC before prostatectomy using ISET®. Disease recurrence was assessed by the increase in serum PSA level after prostatectomy. The following factors were assessed for statistical association with prostate cancer recurrence: the presence of CTC, serum PSA, Gleason score, and pT stage using univariate and multivariate analyses, with a mean follow-up of 34.9 months. Prostate cancer recurrence was significantly associated with the presence of at least 1 CTC at the preoperative time point (p < 0.001; Predictive value = 0.83). Conversely, the absence of prostate cancer recurrence was significantly associated with the lack of CTC detection at diagnosis (Predictive value = 1). Our multivariate analysis shows that only CTC presence is an independent risk factor associated with prostate cancer recurrence after prostatectomy (p < 0.001). Our results suggest that CTC detection by ISET® before surgery is an interesting candidate predictive marker for cancer recurrence in patients with non-metastatic PCa.

A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.

BACKGROUND & 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 = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) 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 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 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 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles 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 scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 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 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Relationships between Attentional Bias and craving in Alcohol Use Disorder: Role of metacognitions.

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.

Sugar, a powerful substitute for ethanol in ethanol postdependent rats: Relevance for clinical consideration?

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.

Sugar intake and craving during alcohol withdrawal in alcohol use disorder inpatients.

To assess whether changes in sugar intake and craving 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 and 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, whereas no change was observed in the remaining 21. Significant increases in both the amounts of sweet products stored in the patients' rooms (p < 0.02) and weight (p < 0.05) were observed only in the sugar craving group. During the same period, alcohol craving decreased significantly in all patients. Changes in tobacco smoking were not different according to the sugar craving status and therefore cannot explain the observed differences. In conclusion, increased intake and craving for sugar after alcohol withdrawal were observed in 40% of the patients included in our prospective study, and these results were similar to those of a study conducted in the alcohol post-dependent state model in rats.

Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers.

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 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). 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.

Genome-wide Association Study and Meta-analysis on Alcohol-Associated Liver Cirrhosis Identifies Genetic Risk Factors.

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 × 10-17 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10-10 ) 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 × 10-8 ) 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.

Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing.

Despite the astonishing progress in treating chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents, liver fibrosis remains a major health concern in HCV infected patients, in particular due to the treatment cost and insufficient HCV screening in many countries. Only a fraction of patients with chronic HCV infection develop liver fibrosis. While there is evidence that host genetic factors are involved in the development of liver fibrosis, the common variants identified so far, in particular by genome-wide association studies, were found to have limited effects. Here, we conducted an exome association study in 88 highly selected HCV-infected patients with and without fibrosis. A strategy focusing on TGF-ß pathway genes revealed an enrichment in rare variants of the endoglin gene (ENG) in fibrosis patients. Replication studies in additional cohorts (617 patients) identified one specific ENG variant, Thr5Met, with an overall odds ratio for fibrosis development in carriers of 3.04 (1.39-6.69). Our results suggest that endoglin, a key player in TGF-ß signaling, is involved in HCV-related liver fibrogenesis.

Comparison of e-cigarette use characteristics between exclusive e-cigarette users and dual e-cigarette and conventional cigarette users: an on-line survey in France.

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.

Role of Patient Sex in Early Recovery from Alcohol-Related Cognitive Impairment: Women Penalized.

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 < 26) and reassessed at 6 weeks (n = 395). A logistic regression model was built to determine the influence of sex on recovery status (MoCA < 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 < 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.

Comparison of the MoCA and BEARNI tests for detection of cognitive impairment in in-patients with alcohol use disorders.

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 ±â€¯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.

Determination of MoCA Cutoff Score in Patients with Alcohol Use Disorders.

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.

Maintenance of Abstinence in Self-Help Groups.

AIM: To analyse abstinence rates 12 months after alcohol cessation in a sample of French subjects participating in support group meetings. METHOD: The project was co-designed with support group representatives, and co-investigator roles were delegated to meeting managers. Subjects who had stopped drinking for <3 months were included. An independent investigator evaluated alcohol intake and group attendance every 3 months using a questionnaire, and time to first drink was analysed using survival curves. RESULTS: Overall, 145 participants were included, mean age 47 years. At 1 year, 43% of the 119 who could be evaluated were abstinent. Relapse rates did not differ by gender, withdrawal method, previous stays in a rehabilitation unit or time of first contact with the self-help association. However, participants receiving specialist medical and/or psychological support in addition to attending group meetings had a significantly lower abstinence rate than those who only attended group meetings, although their attendance at group meetings was similar. CONCLUSION: Self-help associations can participate in rigorous scientific studies. The present results identified a subgroup of individuals with alcohol problems who attended self-help groups, but not traditional care pathways. Having additional specialist support was not associated with better outcome.

Evaluation of laboratory tests for cirrhosis and for alcohol use, in the context of alcoholic cirrhosis.

Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women). Comparisons were also made between 631 cases who had reportedly been abstinent from alcohol for over 60 days and 364 who had not. ROC curve analysis was used to estimate and compare tests' ability to distinguish patients with and without cirrhosis, and abstinent and drinking cases. The best tests for presence of cirrhosis were INR and bilirubin, with areas under the ROC curve (AUCs) of 0.91 ± 0.01 and 0.88 ± 0.01, respectively. Confining analysis to patients with no current or previous ascites gave AUCs of 0.88 ± 0.01 for INR and 0.85 ± 0.01 for bilirubin. GGT and AST showed discrimination between abstinence and recent drinking in patients with cirrhosis, including those without ascites, when appropriate (and for GGT, sex-specific) limits were used. For AST, a cut-off limit of 85 units/L gave 90% specificity and 37% sensitivity. For GGT, cut-off limits of 288 units/L in men and 138 units/L in women gave 90% specificity for both and 40% sensitivity in men, 63% sensitivity in women. INR and bilirubin show the best separation between patients with alcoholic cirrhosis (with or without ascites) and control patients with similar lifetime alcohol exposure. Although AST and GGT are substantially increased by liver disease, they can give useful information on recent alcohol intake in patients with alcoholic cirrhosis when appropriate cut-off limits are used.

BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease.

The molecular mechanisms of hepatocellular carcinoma (HCC) carcinogenesis are still not fully understood. DNA repair defects may influence HCC risk. The aim of the study was to look for potential genetic variants of DNA repair genes associated with HCC risk among patients with alcohol- or viral-induced liver disease. We performed four case-control studies on 2,006 European- (Derivation#1 and #2 studies) and African-ancestry (Validation#1 and #2 studies) patients originating from several cohorts in order to assess the association between genetic variants on DNA repair genes and HCC risk using a custom array encompassing 94 genes. In the Derivation#1 study, the BRIP1 locus reached array-wide significance (Chi-squared SV-Perm, P=5.00×10-4) among the 253 haplotype blocks tested for their association with HCC risk, in patients with viral cirrhosis but not among those with alcoholic cirrhosis. The BRIP1 haplotype block included three exonic variants (rs4986763, rs4986764, rs4986765). The BRIP1 'AAA' haplotype was significantly associated with an increased HCC risk [odds ratio (OR), 2.01 (1.19-3.39); false discovery rate (FDR)-P=1.31×10-2]. In the Derivation#2 study, results were confirmed for the BRIP1 'GGG' haplotype [OR, 0.53 (0.36-0.79); FDR-P=3.90×10-3]. In both Validation#1 and #2 studies, BRIP1 'AAA' haplotype was significantly associated with an increased risk of HCC [OR, 1.71 (1.09-2.68); FDR-P=7.30×10-2; and OR, 6.45 (4.17-9.99); FDR-P=2.33×10-19, respectively]. Association between the BRIP1 locus and HCC risk suggests that impaired DNA mismatch repair might play a role in liver carcinogenesis, among patients with HCV- or HBV-related liver disease.

Effectiveness of a web-based intervention to reduce alcohol consumption among French hazardous drinkers: a randomized controlled trial.

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.

Use of Psychoactive Medication in Short- and Long-term Abstainers from Alcohol.

AIM: To document the use of prescribed psychoactive medicines in France in patients recovering from alcohol use disorders (AUDs). METHOD: Survey among short- and long-term abstainers attending groups of French self-help associations for AUDs, recording socio-demographic profile, duration of abstinence, prescription of psychoactive medication and attitudes towards that, and whether or not in medical or psychological follow-up for AUD. RESULT: Five hundred seventy-five abstainers participated. More than a half had stopped drinking for at least 5 years. About 25% of the very long-term abstainers were still in follow-up. Benzodiazepines, then antidepressants, were the most frequently used medication. Prescriptions of medication decreased with length of abstinence; was always higher in women than in men and in those with a medical follow-up. About 45% claimed that they were 'dependent' on their pills. Ten years after having stopping drinking, 19 and 42.1% of men and women, respectively, were still under medication. Cluster analysis of self-opinion on medication showed that in ~30% of the subjects medication seemed to be prescribed for precautionary reasons. CONCLUSION: Psychoactive medication in France is frequently prescribed for years following alcohol withdrawal. While it is possible that this is over-prescription, and further work in this regard is needed, changes in an on-going treatment for a given patient would need to be cautious. SHORT SUMMARY: Psychoactive medication in alcohol use disorders often prescribed for long-term abstainers in France. Benzodiazepines and antidepressants are the most frequently prescribed drugs. Prescription is more frequent in women and in those subjects having medical follow-up for their alcohol problem. Over-prescription is discussed.

Follow-Up of Alcohol Consumption After Liver Transplantation: Interest of an Addiction Team?

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.