Liver fibrosis staging using supersonic shear imaging : a clinical study on 142 patients

International audienceI. Background, Motivation and ObjectiveFibrosis staging can be assessed by a rough estimation of the liver stiffness averaged along an ultrasonic A-line. Providing a complete 2D map of liver stiffness would thus be of great clinical interest for the diagnosis of hepatic fibrosis and help prevent upcoming cirrhosis. However, such measurement requires both a quantitative value of shear elasticity and a great precision to discriminate between different fibrosis levels. Beyond the scope of non-invasive fibrosis quantification, it is also envisioned that quantitative elasticity imaging of liver will have potential interest for liver cancer diagnosis. In this work, the Supersonic Shear Imaging technique (SSI) is proposed to map the in vivo viscoelastic parameters of liver on patients with hepatitis C and derive a mean elasticity of liver tissues. The results are compared to biological tests (Fib4, Apri, Forns) and Fibroscan® measurements. II. Statement of Contribution / MethodsThe SSI technique is based on the radiation force induced by a conventional ultrasonic probe to generate a planar shear wave deep into tissues. The shear wave propagation throughout the medium is caught in real time thanks to an ultrafast ultrasound scanner (up to 5000 frames/s). Using modified sequences and post-processing, this technique is implemented on curved arrays in order to get a larger field of view of liver tissues. A study on 150 HCV patients with different fibrosis stages F has been conducted in order to investigate the accuracy of the technique (F ϵ [0;4]). Quantitative maps of liver elasticity are produced for each volunteer with a linear and a curved array. III. ResultsB-mode images of 120x75 mm² and corresponding elasticity maps are obtained using a 2.5 MHz curved ultrasonic probe with a good reproducibility and accuracy. The shear wave phase velocity dispersion is also calculated. This study shows a good correlation between the values obtained by SSI and the fibrosis levels diagnosed by biological tests (p-index 0.9 for F>3 and Y> 0.8 for F>2). Results are also compared (r2 > 0.92) to the Fibroscan® elasticity measurement by fitting the velocity dispersion curves obtained by SSI at 50 Hz.IV. Discussion and ConclusionsThis real-time elasticity mapping using an ultrasonic curved probe offers better signal to noise ratio than linear arrays and a larger area in the patient's liver (13.3±2.8 cm² estimation area). This gives more confidence on the accuracy of the diagnosis of the fibrosis stage. Furthermore, the elasticity parameters obtained with SSI give access to the shear wave group velocity and the phase velocity. As a consequence, the SSI assessment of liver stiffness could potentially give more information on the viscoelasticity properties of the liver

Grazoprevir/elbasvir combination therapy for HCV infection

Interferon-free regimens combine different second-wave direct-acting antiviral agents (DAAs), which target the main viral proteins involved in the replication cycle of hepatitis C virus (HCV): NS3/4A protease inhibitors (simeprevir or paritaprevir boosted by ritonavir), NS5B nucleos(t)idic (sofosbuvir) and nonnucleos(t)idic (dasabuvir) polymerase inhibitors, NS5A replication complex inhibitors (daclatasvir, ledipasvir, elbasvir, velpatasvir). Combinations of two or three DAAs, given for 8–24 weeks reach sustained virology response (SVR) rates greater than 90% with good tolerance. SVR rates and safety are similar in clinical trials and in real life, usually higher than 95% in the per-protocol analysis. Next-generation DAAs are now expected. To be competitive, these new combinations need to prove their added value regarding the pill burden, the reduced duration of treatment, the drug–drug interaction profile and safety. Zepatier is a fixed-dose combination product coformulating MK-5172 [grazoprevir (GZR), 100 mg QD] and MK-8742 [elbasvir or (EBR) 50 mg QD]: it combines highly potent inhibitors of the HCV NS3/4A protease and NS5A replication complex, respectively. This review provides a summary of the main evidence available for the use of GZR/EBR and highlights the strength of this combination

Utilisation diagnostique et pronostique de l'amplicor HBV monitor test (PRC) chez les patients ADN VHB négatifs en hybridation

But : La quantification de l'ADN du VHB repose sur des techniques d'hybridation moléculaire (seuil de détection entre 7x105 et 106 copies /ml. Les techniques récentes de détection plus sensibles par polymerase chain reaction (PCR) (seuil à 200 copies/ml) posent de nouvelles questions. Le but de ce travail est d'évaluer la valeur pronostique du taux d'ADN viral B par PCR afin de déterminer s'il existe une valeur permettant de discriminer parmi les porteurs chroniques de l'Ag HBs présentant un tableau de portage inactif au moment de la sélection, les vrais porteurs inactifs (porteurs sains), les patients ayant une hépatite chronique avec une suppression virale soutenue (inactivateurs) et ceux ayant un risque de réactivation virale (réactivateurs). Patients et méthodes : 34 porteurs sains, 23 patients inactivateurs et 11 patients réactivateurs ont eu 1 à 3 déterminations de la charge virale par PCR (Test Cobas Amplicor HBV Monitor) pendant une période où les transaminases étaient normales, l'Ag Hbe négatif, les Ac anti-Hbe positifs et l'ADN du VHB négatif en hybridation. Résultat : 18% des patients ont une PCR négative (18% de porteurs sains, 26% des inactivateurs et aucun des réactivateurs). Il existe une différence significative des médianes de virémie entre les porteurs sains (3,07 log 10 copies / ml (2-4,97)) et les réactivateurs (4,67 log 10 copies/ml (2,92-5,99)) (p<0,01), les inactivateurs (3,55 log 10 copies/ml (2-4,81)) et les réactivateurs (p<0,02). Il n'y a pas de différence significative entre les porteurs et les inactivateurs. Les virémies sont inférieures à 105 copies/ml chez les porteurs sains et les inactivateurs. Elles sont stables chez les porteurs sains et tendent à décroître en fonction du temps chez les inactivateurs. Elles sont stables et significativement plus élévées chez les réactivateurs.PARIS7-Villemin (751102101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

An update on the management of hepatitis C virus-infected patients with stage 4-5 chronic kidney disease while awaiting the revised KDIGO Guidelines.

The treatment of hepatitis C virus (HCV) infection has progressed markedly over the last 2 decades, with a dramatic acceleration the last 3 years. The combination of two or three direct-acting antiviral drugs (DAAs) targeting viral proteins [NS3/4A protease inhibitors, NS5B nucleos(t)idic and non-nucleos(t)idic polymerase inhibitors, NS5A replication complex inhibitors], with or without ribavirin but without interferon (interferon-free regimen), for 8-24 weeks, achieved high sustained virological response (>90%), whatever fibrosis stage, genotype and subtype, baseline viral load, prior therapeutic history of the patient (naïve or experienced) and pre-existing resistance-associated variants with a fair tolerance and reduced pill burden. International guidelines recommend to ideally treat all infected patients even if a prioritization of the most severe patients (extensive fibrosis or cirrhosis, symptomatic cryoglobulinaemic vasculitis…) appears to be the best cost-effective and urgent policy. Patients with stage 4-5 chronic kidney disease (CKD) have to be considered as priority patients. Updating of the Kidney Disease: Improving Global Outcomes recommendations is due to start soon, but awaiting their availability, we present here an overview of recent developments in the field

Direct-Acting Antivirals and the Risk of Hepatocellular Carcinoma: The End of a Polemic?

International audienc

L’index FIB-4 pour faire le diagnostic de fibrose hépatique avancée au cours de la stéatose hépatique

International audienceKey pointsThe FIB-4 index is a biomarker of advanced hepatic fibrosis in a context of fatty liver disease.The calculation of the FIB-4 index requires of age, serum ALT and AST transaminase levels and platelet count.A FIB-4 index 1.45 in a context of fatty liver disease.A complete hepatological workup is mandatory for a FIB-4 index > 3.25 in a context of fatty liver disease.Points essentielsL’index FIB-4 est un biomarqueur simple pour diagnostiquer la fibrose hépatique avancée dans un contexte de stéatose.Le calcul de l’index FIB-4 nécessite de connaître l’âge, les transaminases ALT et AST et le taux de plaquettes.Un index FIB-4 1,45 dans un contexte de stéatose indique des explorations complémentaires, par exemple une élastométrie.Un index FIB-4 > 3,25 dans un contexte de stéatose évoque une fibrose hépatique avancée et indique une évaluation hépatologique complète

Pathological evolution of hepatitis C virus-“Healthy carriers”

AIM: To determine factors associated with fibrosis progression in hepatitis C virus (HCV)-infected patients without significant initial pathological lesions. METHODS: Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score ≤ 3, with 2 liver biopsies and detectable HCV-RNA were included. Markers of fibrosis progression were assessed. RESULTS: Median duration of infection and time between paired biopsies was 13 (95% CI: 1-28) and 4 (95% CI: 2-16) years respectively. Alanine-transaminase (ALT) activity was normal in 43.4% of cases. 50% demonstrated progression of the necro-inflammation and 34% of fibrosis after a median time evolution of 4 years (95% CI: 2-16). The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression (P = 0.03) was observed in patients with body mass index (BMI) > 25. Fibrosis progression correlated with the time interval between biopsies (P = 0.01). A significant progression of activity (1.7 vs 0.4, P < 0.05) or fibrosis (0.9 vs 0.0, P < 0.01) was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression (P = 0.003). Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI > 25 and the time interval between 2 biopsies. CONCLUSION: There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI > 25