Plasma carnitine is associated with fatigue in chronic hepatitis C but not in irritable bowel syndrome : Carnitine and fatigue in hepatitis C

International audienceObjectives Fatigue is an important determinant of altered quality of life in patients affected by chronic hepatitis C (CHC) or the irritable bowel syndrome (IBS). In this study, we aimed at determining the contributory role of plasma levels of leptin and carnitine on fatigue in CHC and IBS. Methods We enrolled 70 patients with CHC, 42 with IBS and 44 healthy subjects. Fatigue was evaluated using the Fatigue Impact Scale questionnaire. Body composition was assessed through impedance analysis. Plasma carnitine and leptin were measured. Results Fatigue scores were significantly more elevated in patients with CHC and IBS than in healthy subjects. Patients with CHC, but not with IBS, had significant lower plasma levels of total and free carnitine adjusted for fat mass compared to healthy subjects. In patients with CHC, and not with IBS, fatigue scores were negatively correlated with plasma levels of carnitine. Levels of free carnitine were significantly and independently associated with the severity of fatigue in patients with CHC (OR=2.019, p=0.02, CI 95% [1.01-1.23]).Conclusions In patients with CHC, the severity of fatigue is associated with low level of carnitine, suggesting that an oral supplementation may be effective to relieve fatigue in CHC. The underlying mechanism of fatigue in IBS does not seem to involve carnitine

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

peer reviewedBackground: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010

Etude de la fatigue chez les malades porteurs d'une hépatite chronique virale C (thèse)

NICE-BU Médecine Odontologie (060882102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evaluation des d-dimères comme facteur prédictif précoce de gravité des pancréatites aigües

La pancréatite aiguë (PA) est une pathologie potentiellement grave, pouvant être responsable d une morbidité élevée voire de décès. Certaines de ces complications peuvent être prévenues par une prise en charge adaptée précoce, avec notamment une orientation dans un service spécialisé de soins intensifs ou de réanimation, un remplissage vasculaire et une nutrition entérale. Toute la difficulté de cette pathologie réside dans la détection précoce des formes graves. En effet, les marqueurs pronostiques validés actuellement n évaluent la gravité qu à partir de 48-72 heures. Ces PA graves s accompagnent dès la phase initiale de troubles de la microcirculation entrainant un état d hypercoagulabilité et l activation de la fibrinolyse, et parfois une coagulation intra-vasculaire disséminée. Il en résulte une modification des marqueurs de la coagulation parmi lesquels une élévation des d-dimères. Le but de cette étude était d évaluer le caractère prédictif précoce des d-dimères dans les PA graves. Il s agit d une étude prospective, monocentrique, portant sur 71 patients admis au Centre Hospitalo-Universitaire de Nice pour PA, d octobre 2010 à avril 2012. Etaient exclus les faux positifs des d-dimères, notamment une cirrhose, un traitement par AVK, un cancer, une infection ou un accident thromboembolique récent ou en cours associés. Chaque patient bénéficiait d un dosage des d-dimères dès l admission, puis deux fois par jour pendant les 4 jours suivants l apparition de la douleur. En parallèle, les différents scores pronostics validés, comme le score de Ranson, la CRP et le score de Balthazar, étaient recueillis. Etaient également recueillis le terrain, le service, la durée d hospitalisation, ainsi que la nécessité d une nutrition artificielle et la survenue de complications. Les deux étiologies les plus représentées étaient la cause biliaire dans 42,2 % des cas et alcoolique dans 33,8 % des cas. Sur les 71 patients admis dans le service, 41 patients avaient une PA classée sévère (soit 57,7 %) selon les critères d Atlanta, le taux de CRP, le score de Ranson et de Balthazar. Trente pancréatites graves (42,3 %) ont nécessité une hospitalisation dans un service de soins intensifs ou de réanimation. Le taux de décès était de 2,8 %. Un taux de d-dimères supérieur à 1474 ng/ml à 48 heures de la douleur, était corrélé à la gravité de façon significative (p < 0,05) avec une sensibilité de 80,4 % et une spécificité de 73,3 %. Il était également corrélé de façon significative avec la survenue de complications, telles qu un état de choc, un syndrome de détresse respiratoire aigue, un syndrome de réponse inflammatoire systémique, une insuffisance rénale ou une infection de nécrose (p < 0,05). A 36 heures du début des symptômes, les d-dimères prédisaient également la gravité de la PA avec une sensibilité de 74,2 % et une spécificité de 69,2 % pour un taux supérieur à 1474 ng/ml. Dès 36 heures, les d-dimères sont prédictifs de gravité dans la PA mais aussi de survenue de complications. L utilisation de ce marqueur simple, facilement réalisable et reproductible en pratique clinique pourrait améliorer la prise en charge précoce des PA graves.NICE-BU Médecine Odontologie (060882102) / SudocSudocFranceF

Dépistage et prévention de la consommation d'alcool chez la femme enceinte suivie par la protection maternelle et infantile des Alpes-Maritimes

NICE-BU Médecine Odontologie (060882102) / SudocSudocFranceF

Gastrojejunocolic fistula after gastric surgery for duodenal ulcer: case report

Gastrojejunocolic fistulae, a late complication of gastroenterostomy, are presently uncommon. Patients can present with symptoms of a fistula 20 years or more after their original gastric surgery. The knowledge of this rare condition can allow prevention, through a better operative strategy and a medical treatment at the phase of stomal ulcer with proton pump inhibitor and Helicobacter pylori eradication. We present a case of gastrojejunocolic fistula and discuss the modern management of this condition. Its etiological, clinical, and surgical features were briefly discussed

Efficacy of ferric carboxymaltose on haemoglobin response among older patients with gastrointestinal bleeding: a randomised clinical trial

International audienceAbstract Background Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied. Aims This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB. Methods This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9–11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180. Results From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups. Conclusions Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585)

Pancreatology

BACKGROUND: PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. METHODS: We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. RESULTS: We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. CONCLUSIONS: The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection