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

Engaging HIV-HCV co-infected patients in HCV treatment: the roles played by the prescribing physician and patients' beliefs (ANRS CO13 HEPAVIH cohort, France)

<p>Abstract</p> <p>Background</p> <p>Treatment for the hepatitis C virus (HCV) may be delayed significantly in HIV/HCV co-infected patients. Our study aims at identifying the correlates of access to HCV treatment in this population.</p> <p>Methods</p> <p>We used 3-year follow-up data from the HEPAVIH ANRS-CO13 nationwide French cohort which enrolled patients living with HIV and HCV. We included pegylated interferon and ribavirin-naive patients (N = 600) at enrolment. Clinical/biological data were retrieved from medical records. Self-administered questionnaires were used for both physicians and their patients to collect data about experience and behaviors, respectively.</p> <p>Results</p> <p>Median [IQR] follow-up was 12[12-24] months and 124 patients (20.7%) had started HCV treatment. After multiple adjustment including patients' negative beliefs about HCV treatment, those followed up by a general practitioner working in a hospital setting were more likely to receive HCV treatment (OR[95%CI]: 1.71 [1.06-2.75]). Patients followed by general practitioners also reported significantly higher levels of alcohol use, severe depressive symptoms and poor social conditions than those followed up by other physicians.</p> <p>Conclusions</p> <p>Hospital-general practitioner networks can play a crucial role in engaging patients who are the most vulnerable and in reducing existing inequities in access to HCV care. Further operational research is needed to assess to what extent these models can be implemented in other settings and for patients who bear the burden of multiple co-morbidities.</p

Nutrients

BACKGROUND: Coffee intake has been shown to modulate both the effect of ethanol on serum GGT activities in some alcohol consumers and the risk of alcoholic cirrhosis in some patients with chronic diseases. This study aimed to analyze the impact of coffee intake and alcohol consumption on advanced liver fibrosis (ALF) in HIV-HCV co-infected patients. METHODS: ANRS CO13-HEPAVIH is a French, nationwide, multicenter cohort of HIV-HCV-co-infected patients. Sociodemographic, behavioral, and clinical data including alcohol and coffee consumption were prospectively collected using annual self-administered questionnaires during five years of follow-up. Mixed logistic regression models were performed, relating coffee intake and alcohol consumption to ALF. RESULTS: 1019 patients were included. At the last available visit, 5.8% reported high-risk alcohol consumption, 27.4% reported high coffee intake and 14.5% had ALF. Compared with patients with low coffee intake and high-risk alcohol consumption, patients with low coffee intake and low-risk alcohol consumption had a lower risk of ALF (aOR (95% CI) 0.24 (0.12(-)0.50)). In addition, patients with high coffee intake had a lower risk of ALF than the reference group (0.14 (0.03(-)0.64) in high-risk alcohol drinkers and 0.11 (0.05(-)0.25) in low-risk alcohol drinkers). CONCLUSIONS: High coffee intake was associated with a low risk of liver fibrosis even in HIV-HCV co-infected patients with high-risk alcohol consumption

PLoS One

BACKGROUND: Direct-acting antivirals (DAA) have dramatically increased HCV cure rates with minimal toxicity in HIV-HCV co-infected patients. This study aimed to compare the socio-behavioral characteristics of patients initiating pegylated-interferon (PEG-IFN)-based HCV treatment with those of patients initiating DAA-based treatment. METHODS: ANRS CO13 HEPAVIH is a national multicenter prospective cohort started in 2005, which enrolled 1,859 HIV-HCV co-infected patients followed up in French hospital outpatient units. Both clinical/biological and socio-behavioral data were collected during follow-up. We selected patients with socio-behavioral data available before HCV treatment initiation. RESULTS: A total of 580 patients were included in this analysis. Of these, 347 initiated PEG-IFN-based treatment, and 233 DAA-based treatment. There were significant differences regarding patient mean age (45 years+/-6 for the PEG-IFN group vs. 52 years+/-8 for the DAA group, p<0.001), unstable housing (21.4% vs. 11.2%, p = 0.0016), drug use (44.7% vs. 29.6%, p = 0.0003), regular or daily use of cannabis (24.3% vs. 15.6%, p = 0.0002), a history of drug injection (68.9% vs 39.0%, p<0.0001) and significant liver fibrosis (62.4% vs 72.3%, p = 0.0293). In multivariable analysis, patients initiating DAA-based treatment were older than their PEG-IFN-based treatment counterparts (aOR = 1.17; 95%CI [1.13; 1.22]). Patients receiving DAA treatment were less likely to report unstable housing (0.46 [0.24; 0.88]), cannabis use (regular or daily use:0.50 [0.28; 0.91]; non-regular use: 0.41 [0.22; 0.77]), and a history of drug injection (0.19 [0.12; 0.31]). CONCLUSION: It is possible that a majority of patients who had socio-economic problems and/or a history of drug injection and/or a non-advanced disease stage were already treated for HCV in the PEG-IFN era. Today, patients with unstable housing conditions are prescribed DAA less frequently than other populations. As HCV treatment is prevention, improving access to DAA remains a major clinical and public health strategy, in particular for individuals with high-risk behaviors

The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010

<p>Abstract</p> <p>Background</p> <p>In France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.</p> <p>To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date.</p> <p>Methods</p> <p>Inclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrolment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrolment and yearly thereafter.</p> <p>Results</p> <p>A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrolment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/μl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status.</p> <p>Conclusion</p> <p>The ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.</p

Reversible Decrease of Portal Venous Flow in Cirrhotic Patients: A Positive Side Effect of Sorafenib

Portal hypertension, the most important complication with cirrhosis of the liver, is a serious disease. Sorafenib, a tyrosine kinase inhibitor is validated in advanced hepatocellular carcinoma. Because angiogenesis is a pathological hallmark of portal hypertension, the goal of our study was to determine the effect of sorafenib on portal venous flow and portosystemic collateral circulation in patients receiving sorafenib therapy for advanced hepatocellular carcinoma. Porto-collateral circulations were evaluated using a magnetic resonance technique prior sorafenib therapy, and at day 30. All patients under sorafenib therapy had a decrease in portal venous flow of at least 36%. In contrast, no specific change was observed in the azygos vein or the abdominal aorta. No portal venous flow modification was observed in the control group. Sorafenib is the first anti-angiogenic therapy to demonstrate a beneficial and reversible decrease of portal venous flow among cirrhotic patients

PLoS One

BACKGROUND: The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. METHODS: HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with >/=1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. RESULTS: 1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM 12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR

Cholestase intrahépatique gravidique (facteurs de risque et complications en 2004)

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

Intérêt du dépistage de l'atteinte hépatique chez les patients adultes atteints de mucoviscidose (thèse)

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