Nina Dib

Acoustic radiation force impulse: a new ultrasonographic technology for the widespread noninvasive diagnosis of liver fibrosis.

Background/aims As a module of a standard ultrasound imaging device, acoustic radiation force impulse (ARFI) is a new technology for liver stiffness evaluation (LSE). We aimed to evaluate accuracy, feasibility, reproducibility, and training effect of ARFI for liver fibrosis evaluation. Methods One hundred and one patients with chronic liver disease had LSE by Fibroscan and ARFI. LSE by ARFI was performed in the two liver lobes by two operators: an expert and a novice. Correlation and agreement were evaluated by the Pearson (Rp) and intraclass (Ric) correlation coefficients. The independent reference for liver fibrosis was fibrosis blood tests. Results ARFI results, ranging from 0.7 to 4.6 m/s, were well correlated with Fibroscan results (Rp=0.76). Fibroscan had a significantly higher area under the receiver operating characteristic curve (AUROC) than ARFI for the perprotocol diagnosis of significant fibrosis: 0.890±0.034 versus 0.795±0.047 (P=0.04). However, LSE failure occurred in zero patients using ARFI versus six patients using Fibroscan (P=0.03). Thus, on an intention-to-diagnose basis, Fibroscan and ARFI AUROCs for the diagnosis of significant fibrosis were not different: 0.791±0.049 versus 0.793±0.046 (P=0.98). Interobserver agreement was very good (Ric=0.84) and excellent for ARFI interquartile range (IQR)≤0.30 (Ric=0.91). Indeed, agreement was independently predicted only by ARFI IQR, but not by LSE result as earlier observed for Fibroscan. ARFI AUROC was 0.876±0.057 in patients with ARFI IQR ratio≤0.30, and Fibroscan AUROC was 0.912±0.034 in patients with Fibroscan IQR ratio less than 0.21 (P=0.59). Intersite ARFI agreement between the two liver lobes was fair (Ric=0.60). There was no training effect for LSE by ARFI. Conclusion ARFI is highly feasible and reproducible, and provides diagnostic accuracy similar to Fibroscan. This new device seems noteworthy for the widespread noninvasive diagnosis of liver fibrosis.

The combination of a blood test and Fibroscan improves the non‐invasive diagnosis of liver fibrosis

Background and aims: Blood tests and liver stiffness evaluation (LSE) by ultrasonographic elastometry are accurate tools for diagnosing liver fibrosis. We evaluated whether their synchronous combination in new scores could improve the diagnostic accuracy and reduce liver biopsy requirement in algorithm.

Reproducibility of liver stiffness measurement by ultrasonographic elastometry.

BACKGROUND & AIMS Fibroscan is a noninvasive device that assesses liver fibrosis by liver stiffness evaluation (LSE) with ultrasonographic elastometry. We evaluated LSE reproducibility and its influencing factors. METHODS LSE was performed by 4 experienced physicians (>100 LSEs) in 46 patients with chronic liver disease at 4 different anatomic sites. Additional LSEs were performed for ancillary aims, so that 534 LSEs were available. RESULTS Overall interobserver agreement for LSE results was considered as excellent, with intraclass coefficient correlation (Ric) of 0.93. Low LSE level, nonrecommended sites, LSE interquartile range >25%, and body mass index > or =25 independently decreased agreement. Thus, agreement was fair (Ric = 0.53) for LSE <9 kilopascals and excellent (Ric = 0.90) beyond. The best measurement site for LSE reproducibility was the median axillary line on the first intercostal space under the liver dullness upper limit, with the patient lying in dorsal decubitus. When LSE results were categorized into fibrosis Metavir stages, interobserver discordance was noticed in about 25% of the cases and was the highest for F2 and F3 stages and the lowest for F4. Intraobserver (Ric = 0.94), intersite (Ric = 0.92-0.98), and interequipment (Ric = 0.92) agreements for LSE results were excellent. Preliminary standard ultrasonography or probe pressure changes did not improve interobserver agreement. CONCLUSIONS The best measurement site for LSE is the one generally used for liver biopsy. Reproducibility of LSE is globally excellent but is fair in patient with low liver stiffness. The fibrosis diagnosis by ultrasonographic elastometry in low stages or categorized into fibrosis Metavir stages must be interpreted with caution.

Learning curve and interobserver reproducibility evaluation of liver stiffness measurement by transient elastography

Background/Aims Fibroscan allows liver stiffness examination (LSE) that is well correlated with fibrosis stages. Our main objective was to evaluate LSE learning curve. Methods LSE results of five novice observers with different medical status were compared with those of five expert observers (physicians with >100 examinations) in 250 patients with chronic liver disease. Each novice–expert pair had to blindly examine 50 consecutive patients divided into five consecutive subgroups of 10 patients. Results In each observer group, novice–expert agreement [intraclass correlation coefficient (Ric)] for LSE results was excellent from the first to the last subgroup. Novice–expert agreement for LSE results varied with liver stiffness level: <9 kPa: Ric=0.49; ≥9 kPa: Ric=0.87. Relative difference (%) between novice and expert LSE results was independently associated with the number of valid LSE measurements, and stabilizes around 20–30% after the fourth valid measurement. In each observer group, novice–expert agreement (Ric) for LSE success rate progressively increased as a function of time. Conclusion LSE requires no learning curve: a novice is able to obtain a reliable result after a single training session, whatever the professional status. However, success rate will progressively increase. An LSE with less than four valid measurements should not be considered as reliable.

A new combination of blood test and fibroscan for accurate non-invasive diagnosis of liver fibrosis stages in chronic hepatitis C.

OBJECTIVES:Precise evaluation of the level of liver fibrosis is recommended in patients with chronic hepatitis C (CHC). Blood fibrosis tests and Fibroscan are now widely used for the non-invasive diagnosis of liver fibrosis. Detailed fibrosis stage classifications have been developed to provide an estimation of the liver fibrosis stage from the results of these non-invasive tests. Our aim was to develop a new and more accurate fibrosis stage classification by using new scores combining non-invasive fibrosis tests.METHODS:In all, 729 patients with CHC (exploratory set: 349; validation set: 380) had liver biopsy for Metavir fibrosis (F) staging, and 6 fibrosis tests: Fibroscan, Fibrotest, FibroMeter, Hepascore, FIB-4, APRI.RESULTS:Exploratory set: Fibroscan and FibroMeter were the independent predictors of different diagnostic targets of liver fibrosis. New fibrosis indexes combining FibroMeter and Fibroscan were thus developed for the diagnosis of clinically significant fibrosis (CSF-index) or severe fibrosis (SF-index). The association of CSF- and SF-indexes provided a new fibrosis stage classification (CSF/SF classification): F0/1, F1/2, F2±1, F2/3, F3±1, F4. Validation set: CSF/SF classification had a high diagnostic accuracy (85.8% well-classified patients), significantly higher than the diagnostic accuracies of FibroMeter (69.7%, P<0.001), Fibroscan (63.3%, P<0.001), or Fibrotest (43.9%, P<0.001) classifications.CONCLUSIONS:The association of new fibrosis indexes combining FibroMeter and Fibroscan provides a new fibrosis stage classification. This classification is significantly more accurate than Fibrotest, FibroMeter, or Fibroscan classifications, and improves the accuracy of the non-invasive diagnosis of liver fibrosis stages to 86% without any liver biopsy.

Current management of the complications of portal hypertension: variceal bleeding and ascites

Portal hypertension is one of the main consequences of cirrhosis. It results from a combination of increased intrahepatic vascular resistance and increased blood flow through the portal venous system. The condition leads to the formation of portosystemic collateral veins. Esophagogastric varices have the greatest clinical impact, with a risk of bleeding as high as 30% within 2 years of medium or large varices developing. Ascites, another important complication of advanced cirrhosis and severe portal hypertension, is sometimes refractory to treatment and is complicated by spontaneous bacterial peritonitis and hepatorenal syndrome. We describe the pathophysiology of portal hypertension and the current management of its complications, with emphasis on the prophylaxis and treatment of variceal bleeding and ascites.

FibroMeters: a family of blood tests for liver fibrosis

FibroMeters are blood tests for liver fibrosis with several specificities: two main diagnostic targets (fibrosis stage and area of fibrosis); adaptation to specific causes; and results confirmed by an expert system. Thus, FibroMeters comprise six different tests: one for staging and one for quantitation of liver fibrosis in each of the three main causes of chronic liver disease-chronic viral hepatitis, alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). FibroMeters display a high overall diagnostic accuracy and are the only tests to correctly classify 100% of HCV patients without fibrosis or with cirrhosis. They have 90% predictive values in a higher proportion of patients than with other usual blood tests. A 90% correct classification is available in 100% of HCV patients with the following reliable diagnostic intervals: F0/1, F1/2, F2+/-1, F3+/-1. In real-life conditions, the reproducibility of FibroMeters is higher than that of liver biopsy or ultrasonographic elastometry. FibroMeters are robust tests with the most stable diagnostic performance across different centers. Optional tests are also available, such as a specific one for cirrhosis, which has a diagnostic accuracy of 93.0% (AUROC: 0.92) and a 100% positive predictive value for diagnosis of HCV cirrhosis. Determination by FibroMeters of the area of fibrosis - the only direct, non-invasive, quantitative measurement of liver fibrosis - are especially useful for following-up cirrhosis as it correlates well with clinical events. FibroMeters are also very accurate in HVB or HIV-HCV co-infected patients. The tests specific for ALD and NAFLD also have a high diagnostic accuracy (AUROCs: 0.96 and 0.94, respectively, for significant fibrosis).

Diagnosis of different liver fibrosis characteristics by blood tests in non-alcoholic fatty liver disease.

Aims: Our aim was to develop an accurate, non‐invasive, blood‐test‐based method for identifying the main characteristics of liver fibrosis in non‐alcoholic fatty liver disease (NAFLD).

Optimization and robustness of blood tests for liver fibrosis and cirrhosis.

OBJECTIVES To optimize the performance and feasibility of fibrosis blood tests and evaluate their robustness. DESIGN AND METHODS The derivation population included 1056 HCV patients with liver biopsy and blood markers. Validation populations included 984 patients with various viral hepatitis causes, and Fibroscan and/or liver biopsy and/or blood markers. RESULTS The bootstrap method validated the markers of the original FibroMeter(2G), but not those of Fibrotest and Hepascore, and provided a hyaluronate-free FibroMeter(3G). AUROCs for significant fibrosis were: FibroMeter(2G): 0.853 vs. FibroMeter(3G): 0.851, p=0.489. Compared to FibroMeter(2G), FibroMeter(3G) had a significantly higher patient rate with predictive values ≥90% for significant fibrosis. Accuracy for fibrosis stage classification was: Fibrotest: 37.9%, FibroMeter(2G): 74.9%, and FibroMeter(3G): 86.9% (p<10(-3)). CONCLUSION The bootstrap method validated FibroMeter(2G) and provided a cheaper and more feasible hyaluronate-free FibroMeter(3G) with comparable performance. Compared to binary diagnosis, fibrosis stage classification increased discrimination, with an increased accuracy to 87% for FibroMeter(3G).

Diagnostic non invasif de l’hypertension portale au cours de la cirrhose: Application à la stratégie de la prévention primaire des varices

One of the major complications of cirrhosis is the occurrence of portal hypertension and esophageal varices. At present, universal endoscopic screening of esophageal varices is recommended in association to primary prophylaxis in patients at high risk of variceal bleeding. But this screening is invasive and could be not cost-effective. Besides, pre-primary phrophylaxis is not effective and hampared by side effects. So, non invasive diagnosis of portal hypertension might be useful. This one could depend on non invasive measurement of hepatic venous pressure gradient, but its application to screening is not well-documented and its use in treatment monitoring is debated. A second way could be non invasive diagnosis of large esophageal varices because of prognostic and economic issues. Indirect echographic markers of portal hypertension and esophageal varices (ascites, portal vein diameter > or = 13 mm, spleen length, maximal and mean velocimetry of portal vein flow, respectively < 20 cm/s and < 12 cm/s) could be useful. Among this parameters, spleen length is an independent predictive marker of esophageal varices. Besides, several direct or indirect blood markers of fibrosis have been tested. Platelet count is repeatedly a predictive marker of esophageal varices in multivariate analysis. The other predictive factors of esophageal varices could be: prothrombin time, splenomegaly, spider naevi, Child-Pugh class, bilirubinemia, platelet count/spleen diameter ratio and Fibrotest, but these data require validation. In summary, in regard to actual results, non invasive diagnosis of portal hypertension might be useful in esophageal varices screening, but the substitutes to endoscopy have limited place actually in clinical practice, and exclusive non invasive diagnosis of portal hypertension is not applicable; the only test that seems to be useful in clinical practice is conventional endoscopy awaiting the results of videocapsule.