Etude des facteurs associés à la gravité de la maladie hépatique chez les patients co-infectés par le virus de l'immunodéficience humaine (VIH) et le virus de l'hépatite B (VHB)

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Clinical Usefulness of the Iowa Gambling Task in Severe Alcohol Use Disorders: Link with Relapse and Cognitive-Physiological Deficits.

BACKGROUND: Decision-making impairments have been repeatedly evaluated in severe alcohol use disorders (SAUD) using the Iowa Gambling Task (IGT). The IGT, capitalizing on strong theoretical background and ecological significance, allowed identifying large-scale deficits in this population and is now a standard decision-making assessment in therapeutic settings. However, the clinical usefulness of the IGT, particularly regarding its ability to predict relapse and its link with key cognitive-physiological deficits, remains to be clarified. METHODS: Thirty-eight recently detoxified patients with SAUD and 38 matched healthy controls performed the IGT, a neuropsychological task using monetary rewards to assess decision making under uncertainty and under risk. Disease characteristics (e.g., duration and intensity), cognitive abilities, psychopathological comorbidities, and physiological damage were also measured, as well as relapse rates 6 months later. RESULTS: Compared to controls, patients with SAUD presented a dissociation between preserved decision making under uncertainty and impaired decision making under risk. In the SAUD group, while relapsers (55% of the sample) presented lower global cognitive functioning and stronger liver damage than nonrelapsers at detoxification time, no difference was found between these subgroups for the IGT. IGT results were not related to alcohol-consumption characteristics or cognitive-physiological deficits. CONCLUSIONS: SAUD is not related to a global IGT deficit, as suggested earlier, but rather to a specific impairment for decision making under risk. This deficit is not associated with other disease-related variables and has no relapse prediction power. These results question the clinical usefulness of the IGT as a tool identifying key treatment levers and guiding (neuro)psychological rehabilitation

Characterisation of hepatitis B virus X protein mutants in tumour and non-tumour liver cells using laser capture microdissection

International audienceBackground/Aims: The analysis of hepatitis B virus (HBV) X protein genetic variability and is correlation with liver disease severity have only been addressed, so far, on whole liver extracts. We have studied, therefore, the HBV X protein (HBx) gene sequence in morphologically well-characterised tumour and non-tumour liver cells from patients with HBV-related hepatocellular carcinoma.Methods: Using laser capture microdissection (LCM), we picked up six to eight groups of tumour and non-tumour hepatocytes in serial frozen sections from six patients. After global DNA preamplification followed by HBx-specific polymerase chain reaction, the HBx gene was sequenced in each group of microdissected cells. We also validated the quantification of HBV-DNA in microdissected hepatocytes using HBV Amplicor®.Results: Heterogeneous mutations in HBx gene were found in distinct cirrhotic nodules and tumour areas from the same patient. Mutations at aa 127, 130 and 131 were frequently detected but there was no distinct point mutation profile between tumour and non-tumour samples. In contrast, deletions in HBx gene, which were found in five/six patients, were more frequent in tumour-derived sequences (6/18) than in non-tumour-derived sequences (1/20).Conclusions: We have shown that LCM provides a direct insight of intrahepatic HBV infection. Using this technique, we demonstrated the persistence of distinct HBx encoding sequences in clonally expanding cells, thus supporting the hypothesis that HBx deletions may be implicated in liver carcinogenesis

Magnesium in the treatment of alcohol withdrawal syndrome: a multicenter randomized controlled trial

International audienceObjective: Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebocontrolled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. Material and Methods: Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. Results: A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was −0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. Conclusions: The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS

Intrahepatic hepatitis C virus RNA quantification in microdissected hepatocytes

International audienceBackground/Aims: Debate continues on whether serum and intrahepatic HCV viral loads are correlated and if HCV viral load correlates with the severity of liver disease. These difficulties may at least in part be linked to liver cell heterogeneity, when total liver extracts from HCV-infected individuals are tested for HCV RNA quantification. We have therefore investigated the feasibility of quantifying HCV replication using a laser-based microdissection technique.Methods: We compared the results with those obtained for serum HCV RNA quantification and immunochemistry in the case of HCV antigen detection in the liver. Twenty-one HCV-positive patients with chronic active hepatitis (n=10) or cirrhosis (n=11) were analyzed.Results: A positive correlation (P=0.0019) was observed between HCV RNA quantifications in sera and microdissected cells. Immunohistochemistry demonstrated that HCV antigen hepatocytes were randomly distributed within liver lobules. Their percentage varied in different patients (0–40%), but did not correlate with the HCV viral load.Conclusions: We have designed a sensitive methodology to evaluate the intrahepatic HCV viral load by combining a standardized RNA quantification method with microdissected hepatocytes from frozen liver needle biopsies. Our results directly demonstrate a positive correlation between serum and intrahepatic viral loads, which therefore provides a reliable reflection of intrahepatic HCV replication

Childhood trauma and the severity of past suicide attempts in outpatients with cocaine use disorders

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Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines

International audienceExcessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol-related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Study of the Liver wished to organise guidelines together with the French Alcohol Society in order to summarise the best evidence available about several key clinical points in ARLD. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe how patients with ARLD should be managed nowadays and discuss the main unsettled issues in the field