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. METHODS: Three hundred and ninety patients with chronic liver disease of miscellaneous causes were included. Five blood fibrosis tests were evaluated: APRI, FIB-4, Hepascore, Fibrotest and FibroMeter. The reference was fibrosis Metavir staging. RESULTS: Diagnosis of significant fibrosis (Metavir F>or=2). The most accurate synchronous combination was FibroMeter+LSE, which provided a significantly higher area under the receiver operating characteristic curve (0.892) than LSE alone (0.867, P=0.011) or Fibrometer (0.834, P<10(-3)). An algorithm using the FibroMeter+LSE combination and then a liver biopsy in indeterminate cases had 91.9% diagnostic accuracy and required significantly fewer biopsies (20.2%) than previously published Bordeaux algorithm (28.6%, P=0.02) or sequential algorithm for fibrosis evaluation (SAFE) (55.7%, P<10(-3)). The Angers algorithm performance was not significantly different between viral hepatitis and other causes. Diagnosis of cirrhosis. The most accurate synchronous combination was LSE+FibroMeter, which provided >or=90% predictive values for cirrhosis in 90.6% of patients vs 87.4% for LSE (P=0.02) and 57.9% for FibroMeter (P<10(-3)). An algorithm including the LSE+FibroMeter combination, and then a liver biopsy in indeterminate cases, had a significantly higher diagnostic accuracy than the SAFE algorithm (91.0 vs 79.8%, P<10(-3)), and required significantly fewer biopsies than the Bordeaux algorithm (9.3 vs 25.3%, P<10(-3)). CONCLUSION: The synchronous combination of a blood test plus LSE improves the accuracy of the non-invasive diagnosis of liver fibrosis and, consequently, markedly decreases the biopsy requirement in the diagnostic algorithm, notably to <10% in cirrhosis diagnosis.

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.

Reproducibility of blood tests of liver fibrosis in clinical practice.

OBJECTIVES: To evaluate the inter-laboratory reproducibility of blood test for liver fibrosis: FibroMeter, Fibrotest, APRI and their composites variables. DESIGN AND METHODS: Four studies, including 147 patients, were performed: study #1 included 2 metachronous blood samples and 2 laboratories; studies #2, #3 and #4 included synchronous samples with assays delayed at day 1 in 12 laboratories, at day 0 in 10 laboratories and at day 0 or 1 in 2 laboratories, respectively. Agreement was evaluated by the intraclass correlation coefficient (r(ic)). RESULTS: In studies #1, #2 and #4, r(ic) for FibroMeter was 0.893, 0.942 and 0.991, respectively. In study #3, the r(ic) were: FibroMeter: 0.963, Fibrotest: 0.984, APRI: 0.949. Large simulated variations in composite variables had a weak impact on FibroMeter. CONCLUSIONS: When blood marker limits are controlled, inter-laboratory agreement of blood tests is excellent in clinical practice conditions. Blood tests are robust against the variability of composite blood variables.

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; >or=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.

[Stomal varices treated by glue embolization]. / Embolisation de varices stomiales par injection percutanée de colle biologique.

In patients with cirrhosis and enterostomy, although bleeding stomal varices are rare, they can been severe and difficult to be treat. We report the first two cases of bleeding stomal varices treated by cyanoacrylate embolization, in patients with cirrhosis and colostomy. In each case, after pharmacological treatment of portal hypertension (propranolol) failed, embolization of the stomal varices by transdermal injection of biological glue effectively stopped the bleeding, without recurrence or side effects, after 8 and 16 months of follow-up. The embolization of stomal varices by biological glue is a safe, easy and efficient treatment for bleeding stomal varices.

[Non-invasive diagnosis of portal hypertension in cirrhosis. Application to the primary prevention of varices]. / Diagnostic non invasif de l'hypertension portale au cours de la cirrhose. Application a 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.

Direct percutaneous approach for endoluminal glue embolization of stomal varices.

The present report describes the authors' experience with direct endoluminal embolization for bleeding stomal varices. Between December 1998 and July 2006, seven patients with enterostomies, portal hypertension, and recurrent stomal variceal bleeding resistant to medical treatment were treated at a single institution. Ultrasonography was used to guide direct puncture of the varices. Direct endoluminal embolization with cyanoacrylate glue was performed under fluoroscopic control imaging. Embolization was successful in six of seven cases. One patient with hepatocellular carcinoma and complete portal thrombosis had three recurrences treated with the same technique, with clinical success. Three patients died at 3, 8, and 18 months without recurrence of bleeding. Although further evaluation is indicated, direct percutaneous embolization appears to be a potential alternative treatment for bleeding stomal varices.

A novel panel of blood markers to assess the degree of liver fibrosis.

The objective was to develop new blood tests to characterize different fibrosis parameters in viral and alcoholic chronic liver diseases. Measurements included 51 blood markers and Fibrotest, Fibrospect, ELFG, APRI, and Forns scores. The clinically significant fibrosis was evaluated via Metavir staging (F2-F4), and image analysis was used to determine the area of fibrosis. In an exploratory step in 383 patients with viral hepatitis, the area under the receiving operator characteristic (AUROC) curve for stages F2-F4 in a test termed the "Fibrometer" test combining platelets, prothrombin index, aspartate aminotransferase, alpha2-macroglobulin (A2M), hyaluronate, urea, and age was 0.883 compared with 0.808 for the Fibrotest (P = .01), 0.820 for the Forns test (P = .005), and 0.794 for the APRI test (P < 10(-4)). The Fibrometer AUROC curve was 0.892 in the validating step in 120 patients. The AUROC curve for stages F2-F4 in a test combining prothrombin index, A2M, hyaluronate, and age was 0.962 in 95 patients with alcoholic liver diseases. The area of fibrosis was estimated in viral hepatitis by testing for hyaluronate, gamma-glutamyltransferase, bilirubin, platelets, and apolipoprotein A1 ((a)R(2) = 0.645), and in alcoholic liver diseases by testing for hyaluronate, prothrombin index, A2M, and platelets ((a)R(2) = 0.836). In conclusion, the pathological staging and area of liver fibrosis can be estimated using different combinations of blood markers in viral and alcoholic liver diseases. Whereas the Fibrometer has a high diagnostic accuracy for clinically significant fibrosis, blood tests for the area of liver fibrosis provide a quantitative estimation of the amount of fibrosis, which is especially useful in cirrhosis.