Évolution et facteurs prédictifs de dysthyroïdie induite par l'interféron-alpha chez les malades traités pour hépatite chronique C

La survenue d une dysthyroïdie au cours du traitement par interféron des hépatites chroniques C (HCC) est un effet secondaire connu. Le but de notre étude est de décrire le suivi à long terme de cette complication et d en définir les facteurs prédictifs. 301 malades traités pour une hépatite chronique C entre 1999 et 2004, dans le service d hépato gastroentérologie de l hôpital du Kremlin Bicêtre ont été inclus dans notre étude. Ont été pris comme groupe témoin les malades traités pour une HCC n ayant pas développé de dysthyroïdie durant la même période. 30 malades ont développé une dysthyroïdie (10%) après un délai médian de 5 mois de traitement. L évolution de la dysthyroïdie s est faite sous 3 formes: hypothyroïdie (n=10), hyperthyroïdie (n=12), forme biphasique (n=8). 40% ont récupéré une fonction thyroïdienne normale. Le sexe féminin, la positivité avant traitement des anticorps anti-thyroglobuline, des anticorps anti-peroxydase ainsi qu un score modéré de fibrose apparaissent comme prédictifs de la survenue d une dysthyroïdie sous interféron alpha.PARIS13-BU Serge Lebovici (930082101) / SudocSudocFranceF

Hépatite alcoolique

National audienceAlcoholic hepatitis. In a context of chronic alcoholic intoxication, the diagnosis of alcoholic hepatitis (AH) relies on a histological definition. When it is symptomatic, AH is a clinical syndrome associating jaundice, moderate fever, sensitivity of the right upper quadrant, loss of appetite and signs of hepatocellular insufficiency in severe forms. Typical biological tests show a moderate cytolysis with predominant AST, a high level of ãGT, and leukocytosis on neutrophils. Rising level of bilirubin and INR rates and low TP ratio are markers of severity of the disease. Regardless, the initial severity, abstinence has a decisive influence on long-term survival. In severe forms (Maddrey ≥ 32), corticosteroid for one month improves short-term survival, which response is evaluated by the Lille score. Accelerated procedure liver transplantation may be offered to some non-responders to medical treatment

Marqueurs sériques de fibrose au cours de l'hépatite chronique virale C

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Evolution and predictive factors of thyroid disorder due to interferon alpha in the treatment of hepatitis C

AIM: To study predictive factors of thyroid dysfunction associated with interferon-alpha (IFNα) therapy in chronic hepatitis C (CHC) and to describe its long-term evolution in a large population without previous thyroid dysfunction

Chlordecone potentiates auto-immune hepatitis and promotes brain entry of MHV3 during viral hepatitis in mouse models

International audienceChlordecone is an organochlorine used in the 1970's as a pesticide in banana plantations. It has a long half-life in the soil and can potentially contaminate humans and animals through food. Chlordecone targets, and mainly accumulates in, the liver, leading to hepatomegaly and neurological signs in mammals. Chlordecone does not cause liver injuries or any inflammation by itself at low doses, but it can potentiate the hepatotoxic effects of other chemicals and drugs. We studied the impact of chlordecone on the progression of acute hepatitis in mouse models of co-exposure to chlordecone with Concanavalin A or murine hepatitis virus type 3. We examined the progression of these two types of hepatitis by measuring hepatic transaminase levels in the serum and inflammatory cells in the liver, liver histological studies. Amplified tremors presented in the MHV3- chlordecone mouse model had led us to study the expression of specific genes in the brain. We show that chlordecone amplifies the auto-immune hepatitis induced by Concanavalin A by increasing the number of liver NKT cells, which are involved in liver damage. Chlordecone also accelerated the death of mice infected by murine hepatitis virus and enhanced the entry of the virus into the cervical spinal cord in infected mice, leading to considerable neurological damage. In conclusion, chlordecone potentiates both the Concanavalin A-induced hepatitis and brain damage caused by an hepatotropic/neurotropic virus

Chlordecone potentiates hepatic fibrosis in chronic liver injury induced by carbon tetrachloride in mice

International audienceChronic liver damage due to viral or chemical agents leads to a repair process resulting in hepatic fibrosis. Fibrosis may lead to cirrhosis, which may progress to liver cancer or a loss of liver function, with an associated risk of liver failure and death. Chlordecone is a chlorinated pesticide used in the 1990s. It is not itself hepatotoxic, but its metabolism in the liver triggers hepatomegaly and potentiates hepatotoxic agents. Chlordecone is now banned, but it persists in soil and water, resulting in an ongoing public health problem in the Caribbean area. We assessed the probable impact of chlordecone on the progression of liver fibrosis in the population of contaminated areas, by developing a mouse model of chronic co-exposure to chlordecone and a hepatotoxic agent, carbon tetrachloride (CCl4). After repeated administrations of chlordecone and CCl4 by gavage over a 12-week period, we checked for liver damage in the exposed mice, by determining serum liver transaminase (AST, ALT) levels, histological examinations of the liver and measuring the expression of genes encoding extracellular matrix components. The co-exposure of mice to CCl4 and chlordecone resulted in significant increases in ALT and AST levels. Chlordecone also increased expression of the Col1A2, MMP-2, TIMP-1 and PAI-1 genes in CCl4-treated mice. Finally, we demonstrated, by quantifying areas of collagen deposition and alpha-SMA gene expression, that chlordecone potentiated the hepatic fibrosis induced by CCl4. In conclusion, our data suggest that chlordecone potentiates hepatic fibrosis in mice with CCl4-induced chronic liver injur

Hepatitis B virus-associated hepatocellular carcinoma is still a matter of concern in the French Caribbean Island of Guadeloupe

International audienc

Submucosal hematoma: a new distinctive sign during emergency upper digestive endoscopy for ammonia ingestion

Abstract Background Submucosal hematoma has never been associated with caustic injuries. Long-term follow-up of patients who ingested ammonia is not well known and ammonia ingestion is rare. Methods In a Single-center observational study, prospective data were collected from 2009 to 2013, in patients over the age of 14 years old referred for ammonia ingestion. The emergency and follow-up endoscopic data and the outcome were reported. Results Ammonia ingestion occurred in 43 patients. Submucosal hematoma of the gastric wall was a distinctive endoscopic sign observed in 15 (34.8%) cases. Oropharyngeal lesions were present in 30 (69.8%) patients, which was associated with ingestion with suicidal intent in 18 cases. Mild and severe endoscopic lesions (grade IIB to IIIB) were found in 16 (37.2%) cases with 10 (23.3%) cases presenting submucosal hematoma at initial endoscopy. A complete spontaneous gastric healing was frequently observed in 36 (83.7%) cases. In 11 cases with submucosal hematoma, a favourable outcome was observed with a medical treatment, however 6 of these patients had severe endoscopic lesions initially. Conclusions Submucosal hematoma of the gastric wall is an endoscopic sign occurring frequently in ammonia ingestion. Submucosal hematoma should be distinguished from necrosis in order to avoid false misclassification in favour of more severe lesions, which would lead to an abusive surgery

MELD Score Kinetics in Decompensated HIV+/HCV+ Patients: A Useful Prognostic Tool (ANRS HC EP 25 PRETHEVIC Cohort Study)

International audienceTo assess prognostic factors for survival and describe Model for End-Stage liver disease (MELD) dynamics in human immunodeficiency virus+/hepatitis C virus+ (HIV+/HCV+) patients after an initial episode of hepatic decompensation.An HIV+/HCV+ cohort of patients experiencing an initial decompensation episode within the year preceding enrollment were followed prospectively. Clinical and biological data were collected every 3 months. Predictors for survival were identified using Kaplan-Meier curves and Cox models. A 2-slope-mixed linear model was used to estimate MELD score changes as a function of survival.Sixty seven patients were included in 32 centers between 2009 and 2012 (72% male; median age: 48 years [interquartile ratio (IQR):45-52], median follow-up: 22.4 months [range: 0.5-65.3]). Overall survival rates were 86%, 78%, and 59% at 6, 12, and 24 months, respectively. Under multivariate analysis, the MELD score at initial decompensation was predictive of survival, adjusted for age, type of decompensation, baseline CD4 counts, and further decompensation during follow-up as a time-dependent variable. The adjusted hazard ratio of death was 1.32 for a score 3 points higher (95% CI: [1.06-1.63], P = 0.012). MELD score kinetics within the 6 months after initial decompensation differed significantly between non-deceased and deceased patients, with a decreased (-0.49/month; P = 0.016), versus a flat (+0.06/month, P = 0.753) mean change in score.MELD is an effective tool to predict survival in HIV+/HCV+ patients with decompensated cirrhosis. A non-decreasing MELD score within 6 months following this initial decompensation episode may benefit from privileged access to liver transplantation in this poor prognosis populatio