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International audience; Background In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. Aim To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. Methods In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. Results The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m(2)/month, P=0.03) independently of the pre-treatment eGFR (P=0.99), ribavirin administration (P=0.26), mycophenolate mofetil administration (P=0.51) and stage of fibrosis (F3 and F4 vs lower stages, P=0.18; F4 vs lower stages, P=0.08; F4 Child-Pugh B and C vs lower stages, P=0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m(2)/month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P=0.34, 0.08, 0.73). Conclusion The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

International audience; EASL International Liver Congress, APR 13-17, 2016, Barcelona, SPAIN

International audience; no abstract

International audience; no abstract

International audience; no abstract

Hepatitis C virus (HCV) remains a challenging public health problem worldwide. The identification of viral variants establishing de novo infections and definition of the phenotypic requirements for transmission would facilitate the design of preventive strategies. We explored the transmission of HCV variants in three cases of acute hepatitis following needlestick accidents. We used single-genome amplification of glycoprotein E1E2 gene sequences to map the genetic bottleneck upon transmission accurately. We found that infection was likely established by a single variant in two cases and six variants in the third case. Studies of donor samples showed that the transmitted variant E1E2 amino acid sequences were identical or closely related to those of variants from the donor virus populations. The transmitted variants harbored a common signature site at position 394, within hypervariable region 1 of E2, together with additional signature amino acids specific to each transmission pair. Surprisingly, these E1E2 variants conferred no greater capacity for entry than the E1E2 derived from nontransmitted variants in lentiviral pseudoparticle assays. Mutants escaping the antibodies of donor sera did not predominate among the transmitted variants either. The fitness parameters affecting the selective outgrowth of HCV variants after transmission in an immunocompetent host may thus be more complex than those suggested by mouse models. Human antibodies directed against HCV envelope effectively cross-neutralized the lentiviral particles bearing E1E2 derived from transmitted variants. These findings provide insight into the molecular mechanisms underlying HCV transmission and suggest that viral entry is a potential target for the prevention of HCV infection.

Resume Introduction. – L’avitaminose B1 est une cause classique d’insuffisance cardiaque a debit eleve classiquement liee a l’alcoolisme en Occident, elle peut en fait etre uniquement en rapport avec une carence d’apport alimentaire. Exegese. – Nous rapportons l’observation d’un patient jeune, chez qui la mise en evidence d’un epanchement pericardique a l’echocardiogramme conduit, au cours du bilan etiologique, a la decouverte d’une insuffisance cardiaque a debit eleve en raison d’un deficit en thiamine. Le diagnostic a ete etabli apres le bilan hemodynamique et le dosage sanguin de thiamine. L’evolution a ete favorable par le traitement vitaminique, avec une regression rapide de l’insuffisance cardiaque. Conclusion. – Bien que peu frequent, le diagnostic de beriberi cardiovasculaire doit donc etre systematiquement evoque en presence d’une insuffisance cardiaque a debit eleve. Notre observation permet en outre de rappeler qu’une carence alimentaire de cette vitamine est rare, mais doit etre actuellement recherchee lorsqu’elle est associee a d’autres stigmates de denutrition.

Resume Nous rapportons un cas de carcinome pulmonaire a petites cellules se manifestant initialement par une pseudo-obstruction intestinale chronique et decouvert a l’occasion de l’exploration d’une achalasie du sphincter inferieur de l’œsophage. L’obtention d’une remission tumorale de plus de 21 mois apres radiochimiotherapie n’empechait pas le syndrome paraneoplasique de persister et le traitement medical restait sans effet sur la pseudo-obstruction et la dysphagie qui n’etait amelioree que par une dilatation œsophagienne.

Most clinical studies suggest that the prevalence and severity of liver steatosis are higher in patients infected with hepatitis C virus (HCV) genotype 3 than in patients infected with other genotypes. This may reflect the diversity and specific intrinsic properties of genotype 3 virus proteins. We analyzed the possible association of particular residues of the HCV core and NS5A proteins known to dysregulate lipid metabolism with steatosis severity in the livers of patients chronically infected with HCV. We used transmission electron microscopy to quantify liver steatosis precisely in a group of 27 patients, 12 of whom were infected with a genotype 3 virus, the other 15 being infected with viruses of other genotypes. We determined the area covered by lipid droplets in liver tissues and analyzed the diversity of the core and NS5A regions encoded by the viral variants circulating in these patients. The area covered by lipid droplets did not differ significantly between patients infected with genotype 3 viruses and those infected with other genotypes. The core and NS5A protein sequences of the viral variants circulating in patients with mild or severe steatosis were evenly distributed throughout the phylogenic trees established from all the collected sequences. Thus, individual host factors seem to play a much greater role than viral factors in the development of severe steatosis in patients chronically infected with HCV, including those infected with genotype 3 viruses.

Hepatitis E virus (HEV) is an emerging problem amongst transplant recipients. We report a patient with chronic HEV hepatitis after a heart transplant. The patient received a 3-month course of oral ribavirin (17 mg/kg/day). HEV RNA became undetectable in the serum after 1 month of treatment and remained undetectable in serum and stool samples until the last follow-up, 2 months after completion of ribavirin therapy. The values of liver function indicators returned to normal reference ranges. The main ribavirin-induced side effect was a significant but well-tolerated anemia. We confirmed that ribavirin may induce a sustained virologic response (4 months after ribavirin cessation) in heart transplant patients with chronic HEV infection. Liver cytolysis is rather common in patients after heart transplantation. Rapid evolution to liver fibrosis lesions and available anti-viral therapy highlight the need to look for HEV infection in heart transplant recipients with unexplained hepatitis.

We report a case of a small cell carcinoma of the lung revealed by chronic intestinal pseudo-obstruction associated with achalasia of the lower esophageal sphincter. Tumoral remission was achieved for more than 21 months after chemoradiotherapy but this did not prevent the paraneoplasic syndrome from persisting and medical treatment was not successful in treating the intestinal pseudo-obstruction or the dysphagia, which was not improved by esophageal dilation.

Pregnancy in patients with portal hypertension is rare but worrying for the clinician. Although the effects of portal hypertension during pregnancy have not been fully elucidated, there is an evident increase in morbidity, especially associated with cirrhosis, which justifies the idea of at-risk pregnancy and requires management by a multidisciplinary team. The prevention and treatment of gastrointestinal haemorrhage is quite similar to that in nonpregnant patients. Investigation and management of portal hypertension before and at the beginning of pregnancy can reduce the risks of foetal loss, restricted intra-uterine growth, premature birth and maternal mortality, which are closely related to gastrointestinal haemorrhage. The risks related to the underlying disease, such as liver failure with cirrhosis and thromboembolic risk with vascular diseases associated with thrombophilia must be taken into consideration. Generally, vaginal delivery with early analgesics for the mother assisted by an extraction device should be preferred to caesarean section, which must be reserved for obstetrical indications.

International audience; We prospectively assessed contrast-enhanced sonography for evaluating the degree of liver fibrosis as diagnosed via biopsy in 99 patients. The transit time of microbubbles between the portal and hepatic veins was calculated from the difference between the arrival time of the microbubbles in each vein. Liver biopsy was obtained for each patient within 6 months of the contrast-enhanced sonography. Histological fibrosis was categorized into two classes: (1) no or moderate fibrosis (F0, F1, and F2 according to the METAVIR staging) or (2) severe fibrosis (F3 and F4). At a cutoff of 13 s for the transit time, the diagnosis of severe fibrosis was made with a specificity of 78.57%, a sensitivity of 78.95%, a positive predictive value of 78.33%, a negative predictive value of 83.33%, and a performance accuracy of 78.79%. Therefore, contrast-enhanced ultrasound can help with differentiation between moderate and severe fibrosis.

We report the case of a 37-year-old-man having a chronic myelogenous leukemia, who presented, one month after a splenic acutization, massive gastrointestinal bleeding from ulcerated nodules of the gastric fundus. The histologic examination of one of these nodules showed granulocytic sarcoma. In spite of an endoscopic treatment by sclerotherapy with adrenalined serum, the death occurred during a hemorrhagic recurrence. This observation, which is the third case reported of gastric granulocytic sarcoma during the acutization of a myelogenous chronic leukemia, and the first revealed by fatal gastrointestinal bleeding, shows the particular gravity of gastrointestinal bleeding complicating granulocytic sarcoma.

The aim of this retrospective study was to determine the risk factors of early complications after progressive pneumatic dilation for achalasia.Five hundred four dilations were performed in 237 consecutive achalasic patients between 1980 and 1994 with the same technique: low-pressure pneumatic dilation every other day with balloons of increasing diameter until success criteria were obtained (depending on manometric examination and esophageal x-ray transit performed 24 h after each dilation). Clinical, radiographical, endoscopical, and manometrical data as technical procedure characteristics for patients with perforations or other early complications were compared with those without complications.We observed 15 complications (6% of patients): 7 perforations (3%), 3 asymptomatic esophageal mucosal tears, 4 esophageal hematomas, and 1 fever. Perforations occurred in 6 of 7 patients during the first dilation. The mean age was 68.5 yr in the group with complications versus 56.4 yr for the remainder (p0.05). Two deaths occurred in patients older than 90 yr. Instability of the balloon during dilations was noted in 8 of 15 cases of complications versus 57 of 222 patients (p0.05). No other data differed significantly.This study showed a low prevalence of early complications using this progressive technique. Patients with hiatal hernia, esophageal diverticulum, or vigorous achalasia may safely undergo progressive pneumatic dilation. Only patients older than 90 yr should be referred for progressive pneumatic dilation with caution. Most of perforations arose during the first dilation, but there was no predictive pretherapeutic factor of perforation.

We report the case of a 22-year-old-man having a familial adenomatous polyposis coli treated by total colectomy with ileo-rectal anastomosis. Two years after the operation, an asymptomatic mesenteric fibromatosis appeared which was nonresectable due to mesenteric vessels infiltration. Nine years later, sulindac therapy was started for residual polyps in the rectal stump. This treatment was taken intermittently, during periods of 1 to 8 months, for 6 years. After 4 years of treatment, the tumor was no longer palpable. Four years after sulindac discontinuation, the patient was operated on for suspicion of intestinal adhesion. The mesenteric fibromatosis had completely disappeared and mesenteric vessels were free. This complete macroscopic regression of a desmoid tumor after sulindac therapy emphasizes again the interest of this treatment for mesenteric fibromatosis.

We report the case of a 67-year-old-man presenting with pancreatic acinar cell carcinoma revealed by dermatological manifestations of cytosteatonecrosis and treated by hepatic artery ligation. The pancreatic etiology of these lesions was suspected due to hyperlipasemia, and was confirmed by abdominal computerized tomography showing a pancreatic tumor and multiple liver nodules, and by histological examination of one of these lesions. Because of symptomatic treatment failure, rapid impairment of patient's general condition, and by analogy with the treatment of hepatic metastases of neuroendocrine tumors, hepatic artery ligation was performed. Lipasemia decreased markedly and symptoms disappeared for 45 days. Hepatic artery obstruction may be used for emergency treatment of secreting liver metastases.

We report the fourth case of low-grade gastric MALT lymphoma associated to Helicobacter heilmannii. This spiral organism may be present in the gastric mucosa of animals where it is non pathogenic while, in humans, its presence is always associated with chronic gastritis. In this case, Helicobacter heilmannii was observed in the absence of Helicobacter pylori. Regression of endoscopic and histological lesions after Helicobacter heilmannii eradication suggests its role in gastric lymphoma. This observation underlines the need for searching for Helicobacter heilmannii by careful histological examination, in the absence of Helicobacter pylori, and the importance of its eradication in the treatment of gastric lymphoma.

We report the case of a 61-year-old-man with an eosinophilic esophagitis with esophageal motor disorder associated with toxocariasis. He complained of non cardiac chest pain and had eosinophilia leading to the detection of Toxocara canis infection. Pain persisted despite treatment of toxocariasis. Basal manometry was normal but ambulatory 24-hour manometry-pHmetry showed diffuse esophageal spasm. Ultrasonography showed a thickening of the esophageal musculature in the two inferior thirds of the esophagus. After failure of treatment with sodium cromoglycate steroids and esophageal dilatation, calcium antagonists were partially effective. A long esophageal myotomy was performed permiting the disappearance of symptoms. The histological examination of a side myotomy biopsy showed an eosinophilic infiltration of the esophageal muscle layer. This observation leads to discuss the possible relation between toxocariasis, the esophageal motor disorder and the eosinophilic infiltration of the esophageal muscle layer.

Introduction Le sorafenib est un inhibiteur oral de tyrosine kinase ayant une activite anti-angiogenique. Il a recemment demontre un allongement de la survie chez des patients atteints d’un Carcinome Hepato-Cellulaire (CHC) avance, avec un taux de reponse objective inferieur a 5 %. Compte tenu des limites des criteres RECIST pour l’evaluation du sorafenib dans cette indication, il est imperatif d’evaluer d’autres criteres objectifs pour juger de son efficacite. Les progres realises dans le domaine de l’imagerie ultrasonore avec agents de contraste (ECUS) permettent de realiser des etudes fonctionnelles de la vascularisation des tumeurs et de ses modifications sous l’effet des traitements anti-angiogeniques. L’objectif de ce travail prospectif etait d’evaluer l’effet pharmacodynamique anti-angiogenique du sorafenib chez des patients traites pour un CHC au moyen de l’etude par ECUS des modifications de la micro-vascularisation tumorale. Patients et Methodes 14 patients consecutifs traites par sorafenib dans le cadre de l’Autorisation de Mise sur le Marche (AMM) pour un CHC avance etaient inclus dans cette etude prospective. L’âge median etait de 62 ans (41-70), le sex ratio de 13. 11 des patients etait porteurs d’une cirrhose alcoolique, 2 d’une cirrhose virale C et 1 d’une cirrhose virale B. L’effet anti-tumoral du traitement etait etudie au moyen d’une evaluation fonctionnelle par ECUS de la vascularisation d’une lesion hepatique cible de CHC realisee a l’initiation du traitement, a un mois (M1) et a trois mois (M3). Parallelement un scanner ou une IRM etait realise pour une evaluation selon les criteres RECIST a l’initiation du traitement et a M3, en prenant en compte de l’evolution lesionnelle strictement hepatique. La vascularisation tumorale en ECUS a ete evaluee au moyen de trois parametres par deux echographistes : Aire Sous la Courbe (AUC), Index de Perfusion (PI), Rapport des Pentes de Rehaussement (WIR). L’analyse quantitative de permettait de determiner une diminution, une stabilite, une progression ou un echappement vasculaire. Les donnees RECIST ont ete decrites, pour chaque imagerie classique, par deux radiologues differents. Resultats L’evaluation morphologique a M3 retrouvait 10 maladies « stables » (SD) et 4 progressions (PD). Les patients presentant une diminution vasculaire a M1 (criteres ECUS), soit 5 patients sur 14, persistaient en diminution vasculaire a M3, et presentaient dans 100 % des cas une stabilite morphologique des lesions a M3. Neuf autres patients presentaient a M1 une stabilite vasculaire. A M3, 4 maintenaient une stabilite vasculaire (3 SD et 1PD), 3 presentaient une progression vasculaire (2 PD et 1 SD) et 2 un echappement (2 PD). L’ECUS montrait donc a M3 une efficacite sur le plan vasculaire chez 35 % des patients (5/14) et une stabilisation chez 28,5 % (4/14) tandis que l’imagerie classique ne retrouvait pas de variation morphologique detectable chez 71,4 % d’entre eux (10/14). En cas de diminution vasculaire a M1, L’ECUS avait ici une Valeur Predictive Positive (VPP) de 100 % quant a l’absence de progression a M3 sur le plan des imageries classique et fonctionnelle. Conclusion Par rapport a l’imagerie classique, L’ECUS semble permettre une meilleure discrimination des patients repondant au sorafenib, par le suivi evolutif de la micro-vascularisation tumorale. Elle pourrait egalement determiner precocement les patients qui adopteront le profil de reponse le plus favorable. Il s’agit de la premiere etude decrivant l’evolution des parametres de vascularisation tumorale des CHC traites par sorafenib. Elle devrait etre prolongee par une etude multicentrique, avec un plus grand nombre de patients et un suivi prolonge.

Introduction La thrombose portale est une complication frequente de la cirrhose mais son mecanisme n’est pas clairement etabli [1, 2]. Les modifications des tests d’hemostase dans le systeme porte ont ete peu etudiees. Le test de generation de thrombine (TGT) evalue le potentiel endogene de thrombine refletant l’equilibre entre facteurs pro et anticoagulants. Le but de notre etude etait de comparer les tests d’hemostase et en particulier le TGT dans le systeme porte et la circulation veineuse peripherique chez des malades atteints de cirrhose. Patients et Methodes Les tests d’hemostase (Fragment 1+2 de la prothrombine et D-dimeres, Temps de Quick, TCA, dosages des Facteurs II, V et VIII, fibrinogene, taux fonctionnels d’Antithrombine, proteines C et S, TGT) ont ete mesures dans le sang portal et le sang peripherique, preleves de maniere simultanee chez 28 malades atteints de cirrhose a l’occasion de la mise en place d’un TIPS. Le test non parametrique de Wilcoxon etait utilise pour la comparaison des deux territoires. Resultats Dans le sang portal ; le taux du facteur VIII etait correle a la severite de la cirrhose (p = 0,017) et aux taux des proteines C et S. Au TGT, la valeur mediane du rapport de sensibilite a la thrombomoduline du temoin etait de 1,011 (0,78-1,43). Chez la majorite des patients, ces rapports etaient superieurs a 1,6, temoin d’une resistance a la thrombomoduline en faveur d’une hypercoagulabilite equivalente entre les deux circulations (p = 0,274). Cette resistance a la thrombomoduline etait significativement plus importante chez les patients dont l’atteinte hepatique etait plus severe. Conclusion Cette etude confirme que l’augmentation du facteur VIII est correlee a la gravite de la cirrhose. Elle montre que la cirrhose s’accompagne d’un etat d’hypercoagulabilite globale, plus important au niveau portal et correle a sa severite. Elle suggere la realisation d’etudes complementaires pour preciser l’origine de cette hypercoagulabilite. Remerciements, financements, autres Nous remercions le Fond de Recherche de la SNFGE qui a permis le financement de cette etude.

Introduction L’echographie avec ou sans doppler a une faible sensibilite pour l’evaluation de la fibrose hepatique. Le but de cette etude etait d’evaluer l’apport de l’echographie de contraste dans le diagnostic de la fibrose hepatique severe [1,2]. Materiels et Methodes Cent vingt-trois patients ont ete prospectivement inclus dans 5 centres. La biopsie hepatique et l’echographie avec doppler et contraste ont ete realisees dans un delai de 6 mois. La fibrose a ete evaluee selon la classification METAVIR et l’analyse a compare F0-F1-F2 a F3-F4. L’echographie de contraste a ete realisee sur un Sequioa (Siemens, Allemagne) equipe d’un logiciel specifique dedie a l’imagerie de contraste (CPS), a l’aide d’une sonde de 4 MHz et apres injection intra veineuse de 2 fois 2,4 ml de Sonovue (Bracco, Italie). Une relecture centralisee et aveugle des videos de chaque examen ultrasonore etait realisee en consensus par deux lecteurs experimentes. Le parametre mesure etait le temps de transit separant l’arrivee du contraste dans le tronc porte et dans une veine hepatique. Resultats Les donnees de 81 hommes et 42 femmes (âge median [minimum-maximum] de 49 ans [19–83]) ont ete analysees. La taille mediane de la biopsie hepatique etait de 22 mm [6–66 mm], l’etiologie de la cirrhose etait virale pour 58 patients (47 %), alcoolique pour 26 patients (21 %) et autre pour 37 patients (30 %). Soixante et onze patients (58 %) ont ete classes F0-F1-F2 et 52 (42 %) F3-F4. La concordance inter-radiologues des 99 mesures du temps de transit disponibles etait excellente (coefficient de correlation intra-classe : 0,90 [0,83–0,95]). Un temps de transit inferieur a 13 secondes presentait pour le diagnostic de fibrose severe (F3 ou F4) une specificite de 78,57 %, une sensibilite de 78, 95 %, une valeur predictive positive de 73,33 %, une valeur predictive negative de 83,33 % et une performance de 78,79 %. Apres analyse multivariee combinant les parametres echographiques standards et le temps de transit, il apparait que seuls le temps de transit (OR = 13,8 [5,0-38,3] ) et l’aspect du segment 4 (OR = 3,8 [1,3-11,0]) sont independamment predictifs de la fibrose severe. L’aire sous courbe ROC de ce modele est de 0,84 [0,75-0,92]. Conclusion Le temps de transit porto-sus hepatique est fortement correle a la fibrose. En evaluant l’effet shunt, ce parametre est susceptible d’apporter des informations complementaires aux tests biologiques ou elastometriques. Remerciements, financements, autres Les auteurs remercient les co-investigateurs, les Docteurs : Lebigot J, Oberti F, Galtier JB, Laumonier H, Bernard PH, Blanc JF, Sironneau S, Machet F, Couzigou P, Foucher P, Castera L, Bacq Y. Cette etude a ete financee par le programme PHRC 2004.

Objectifs L’objectif de cette etude etait de demontrer l’efficacite de l’examen echo-Doppler combine a l’echographie de contraste, dans le suivi et le diagnostic de l’obstruction des TIPS. Materiels et methodes Un examen echo-Doppler couleur et pulse (EDCP) est realise chez tous les patients allant beneficier de la pose d’un TIPS, a J-1, J+ 1, a un mois, trois mois, six mois et neuf mois. De meme on mesure les pressions veineuses portales (PVP) avant et apres la pose de TIPS. Les parametres hemodynamiques mesures sont : l’index de resistance hepatique, la vitesse moyenne (VM), et le debit dans le tronc porte, l’artere hepatique et le TIPS. Resultats Un total de 208 EDCP a ete realise chez 32 patients. A J+ l, les VM portale et arterielle hepatique augmentent significativement de 73 % et 40 % respectivement. Les debits portal et arteriel augmentent respectivement de 69 % et 51 %. La PVP diminue de 35 %. Il existe une bonne correlation entre la PVP et la VM portale (r = 0,95, P Conclusion L’EDCP combinee a l’echographie de contraste, nous ont permis un suivi objectif des TIPS et de confirmer quantitativement et qualitativement le diagnostic de leur obstruction.