C. Aubé

Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis

BACKGROUND/AIMS Evaluation of the degree of hepatic fibrosis is especially important in patients with chronic liver disease. Our aim was to study the diagnostic accuracy of abdominal ultrasonography for cirrhosis or fibrosis. METHODS Twenty-three clinical (n=12) and Doppler ultrasonic (n=11) variables were recorded in 243 patients with chronic (alcoholic and viral) liver disease under conditions close to those of clinical practice. Fibrosis was classified into six grades by two pathologists. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables, then by stepwise analysis. RESULTS A) Diagnosis of cirrhosis: 1) whole group (n=243): diagnostic accuracy was globally 84%, and 84% with two variables: spleen length, portal velocity; 2) compensated chronic liver disease (n=191): diagnostic accuracy was globally 85%, and 82% with two variables: liver surface, liver length (right kidney); 3) alcoholic compensated chronic liver disease (n=109): diagnostic accuracy was globally 86%, and 88% with two variables: spleen length, liver length (middle clavicle); 4) viral compensated chronic liver disease (n= 83): diagnostic accuracy was globally 86% and 86% with one variable: liver surface. By subtracting the proportion of patients who could not be investigated due to anatomical limitations, the highest calculated univariate diagnostic accuracy decreased by 7%. B) Diagnosis of fibrosis: diagnostic accuracy was globally 84% for extensive fibrosis. CONCLUSIONS Cirrhosis can be correctly diagnosed in 82-88% of patients with chronic liver disease using a few ultrasonographic signs. However, the diagnostic accuracy of ultrasound is decreased by the anatomical limitations of this technique.

Non-invasive diagnosis of esophageal varices in chronic liver diseases

BACKGROUND/AIMS The primary prevention of bleeding from esophageal varices is a major therapeutic issue requiring early screening of esophageal varices. Our aim was to study the diagnostic accuracy of non-endoscopic means for the diagnosis of esophageal varices. METHODS Sixty-three clinical, biochemical, endoscopic and Doppler ultrasound variables were prospectively recorded in 207 consecutive patients with chronic liver disease. Diagnostic accuracy was evaluated by discriminant analysis, first globally using all variables with diagnostic accuracy > or = 65% in univariate analysis, then by stepwise regression. RESULTS A) whole group (n=207), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 81%, and 81% with 1 variable: irregular liver surface at ultrasound, 2) Diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 80%, and 79% with 2 variables: prothrombin index, gamma-globulins. B) patients with cirrhosis (n=116), 1) diagnosis of esophageal varices: diagnostic accuracy was globally 71%, and 72% with 2 variables: platelet count, prothrombin index, 2) diagnosis of large esophageal varices (grades 2+3): diagnostic accuracy was globally 71%, and 72% with 3 variables: platelet count, prothrombin index, spider naevi. The ROC curve showed that the best threshold for the diagnostic accuracy of platelet count was 160 G/l providing a sensitivity of 80% and a specificity of 58%. Platelet count > or = 260 G/l has a negative predictive value > or = 91%. CONCLUSIONS Using a few non-endoscopic criteria, esophageal varices can be correctly diagnosed in 81% of patients with chronic liver disease and in 71% of patients with cirrhosis. These results show that the non-invasive screening of patients who are candidates for the primary prevention of variceal bleeding is possible, but should be improved before being used in a clinical setting.

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.

Diagnostic et quantification de la fibrose hépatique par IRM de diffusion : résultats préliminaires

Resume Objectif Le diagnostic et la quantification de la fibrose hepatique sont des sujets particulierement importants en hepatologie clinique. La biopsie hepatique en demeure la cle, mais souffre de nombreuses limitations. Le but de cette etude est de definir les possibilites de l’IRM de diffusion pour le diagnostic et la quantification de la cirrhose et de definir les meilleurs parametres de sequences pour ce faire. Materiel et methode Une IRM de diffusion a ete realisee chez 13 patients cirrhotiques et 14 volontaires presumes sains. Une sequence en apnee de 8 coupes a ete realisee avec 4 facteurs b (200, 400, 600, et 800 sec/mm 2 ) et 2 TR differents (3 500 et 5 000 ms. Le coefficient de diffusion a ete calcule (ADCs) pour chaque sequence et correle au score de Child Pugh et au taux d’acide hyaluronique sanguin. Resultats L’ADCs est statistiquement significativement plus bas chez les patients cirrhotiques (2,055 10 -3 ) que chez les patients controles (2,915 10 -3 ) (p 2 et un TR de 5000 ms. Il existait une correlation significative entre l’ADCs et le score de Child Pugh (p 2 et le TR 5 000 ms. Conclusion Notre etude preliminaire montre que l’IRM de diffusion pourrait etre capable de diagnostiquer et eventuellement de quantifier la fibrose hepatique, particulierement en utilisant des valeurs de facteur b egales a 200 sec/mm 2 et a 400 sec/mm 2 .

Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy

Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue. The goal of this study was to assess the clinical use of liver stiffness measurement (LSM) evaluated by supersonic shear imaging (SSI), FibroScan, and acoustic radiation force impulse (ARFI) in a cohort of NAFLD patients who underwent liver biopsy. A total of 291 NAFLD patients were prospectively enrolled from November 2011 to February 2015 at 2 French university hospitals. LSM was assessed by SSI, FibroScan (M probe), and ARFI within two weeks prior to liver biopsy. Calculations of the area under the receiver operating curve (AUROC) were performed and compared for the staging of liver fibrosis. AUROC for SSI, FibroScan, and ARFI were 0.86, 0.82, and 0.77 for diagnoses of ≥F2; 0.89, 0.86, and 0.84 for ≥F3; and 0.88, 0.87, and 0.84 for F4, respectively. SSI had a higher accuracy than ARFI for diagnoses of significant fibrosis (≥F2) (P = 0.004). Clinical factors related to obesity such as body mass index ≥ 30 kg/m2, waist circumference ≥102 cm or increased parietal wall thickness were associated with LSM failures when using SSI or FibroScan and with unreliable results when using ARFI. In univariate analysis, FibroScan values were slightly correlated with NAFLD activity score and steatosis (R = 0.28 and 0.22, respectively), whereas SSI and ARFI were not; however, these components of NAFLD did not affect LSM results in multivariate analysis. The cutoff values for SSI and FibroScan for staging fibrosis with a sensitivity ≥90% were very close: 6.3/6.2 kPa for ≥F2, 8.3/8.2 kPa for ≥F3, and 10.5/9.5 kPa for F4. Conclusion: Although obesity is associated with an increase in LSM failure, the studied techniques and especially SSI provide high value for the diagnosis of liver fibrosis in NAFLD patients. (Hepatology 2016;63:1817‐1827)

Inter-observer and intra-observer variability in hepatology.

Objectives A determination of the inter-observer variability is an important step before determining diagnostic accuracy and requires a specific methodology and statistical tests. The aim of this study was to report the results, characteristics and methodological quality of agreement studies performed in hepatology. Methods A search of published studies yielded 42 that could be used in this evaluation: three were clinical studies, 11 were in the field of endoscopy, 12 in histopathology and 16 in radiology. The studies were described with a grid of 28 items and evaluated with a quality score (QUAS; maximum, 35) including 22 items. Results The following agreement level was noted: intra-observer > inter-observer > inter-centre. The following signs had good agreement. Endoscopy: size and red signs of oesophageal varices; histopathology: cirrhosis, fibrosis and steatosis; Doppler: mean portal vein and superior mesenteric artery velocities, hepatic artery area and perfusion indexes. Frequent methodological weaknesses were noted. The real agreement (such as the kappa index excluding chance), and the prevalence of signs and biases were rarely assessed. Standardized observations (67% of the studies), blind assessment (48%), simultaneous observations (7%), and the recording technique were not frequently used. The mean QUAS was 13 ± 6 with 17 ± 4 in histopathology versus 11 ± 6 in radiology (P < 0.05). Using multiple regression, four variables independently predicted the QUAS with R2 = 0.77: adapted tests, multiple observations, intra-class correlation coefficient and agreement proportion. Conclusions Methodology was often insufficient. Agreement is often measured under biased conditions. Some areas were not or were rarely studied, e.g., biology and ultrasound. The agreement and QUAS were often poor, suggesting the need for studies with improved observation and methodological quality of agreement.

In vivo efficiency of four commercial monopolar radiofrequency ablation systems: a comparative experimental study in pig liver.

Rationale and Objectives:To evaluate the efficiency of 4 radiofrequency (RF) systems by assessing the amount of delivered energy for each thermal induced lesion after perfusion mediated RF ablation and to compare the influence of perfusion mediation types on the energy efficiency. Methods:A total of 43 ablations in 16 male landrace pigs with 4 RF devices were performed strictly according to the manufacturers’ instructions. Total absorbed energy was computed and then related to 3D volumetry obtained after histopathological evaluation. Sixteen ablations were performed under physiological liver perfusion and 27 ablations with occlusion of portal vein, hepatic artery, or both vessels. Energy efficiency values of the RF systems for different vascular occlusion techniques were compared and analyzed by a nonparametrical rank sum test. Results:Under physiological perfusion, the average energy delivered to produce 1-cm3 lesion size was calculated to 1650 ± 929, 3097 ± 389, 8312 ± 2068, and 5493 ± 2306 Watt · s/cm3 for the Berchtold®, RadionicsTM, RadiotherapeuticsTM, and RITA® system, respectively. After perfusion-mediated RF ablation, artery occlusion was not as effective as portal vein occlusion, which reduced the energy to 587 ± 148, 869 ± 276, and 903 ± 394 Watt · s/cm3 for the Berchtold®, RadionicsTM, and RadiotherapeuticsTM system, respectively. The occlusion of vessels, portal vein, and artery or portal vein alone increased the energy efficiency compared with physiological liver perfusion or occlusion of the artery (P = 0,003). Conclusions:Under physiological liver perfusion the open perfused system and the internally cooled system provided the best efficiency values with lowest standard deviations. The energy efficiency was increased markedly for all systems after occlusion of the portal vein either alone or in combination with arterial occlusion. Occlusion of the hepatic artery did not improve the efficiency.

Associations between visceral adipose tissue, inflammation and sex steroid concentrations in men

In men, obesity and the metabolic syndrome are accompanied by decreased testosterone levels, but little is known about the associations between visceral adipose tissue (VAT), VAT‐related inflammation and sex steroids.

late recurrence of a hepatic angiomyolipoma

Angiomyolipomas are benign mesenchymal tumours, mostly of renal origin. Hepatic angiomyolipomas are rare, and radiological and pathological diagnoses may be difficult We report on the first case of hepatic angiomyolipoma recurrence known to us, 6 years after surgical treatment of the initial tumour. Moreover, this hepatic recurrence was associated with renal angiomyolipoma without any stigmata of tuberous sclerosis.

Radiologic versus endoscopic placement of percutaneous gastrostomy in amyotrophic lateral sclerosis: multivariate analysis of tolerance, efficacy, and survival.

PURPOSE To compare percutaneous radiologic gastrostomy (PRG) and percutaneous endoscopic gastrostomy (PEG) in terms of tolerance, efficacy, and survival in patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS Forty patients with ALS (17 men; mean age, 66.1 years; range, 39-83 y) underwent 21 PEG and 22 PRG attempts (including three unsuccessful PEG attempts) from 1999 to 2005. To assess tolerance and efficacy, a successful and well tolerated placement was defined as any successful placement with no major or minor local complications or pain requiring opioid analgesic agents. Univariate analysis was performed for all recorded parameters, followed by multivariate analysis for successful and well tolerated placement, 6-month mortality rate, and survival. RESULTS General success rates were 85.7% for PEG and 100% for PRG. Pain was more frequent in PRGs (81.8% vs 52.4%; P = .05). Successful and well tolerated placement was seen in 81.8% of PRGs and 57.1% of PEGs (P = 0.1). Advanced age (P = .02) and PRG (P = .07) were predictive of successful and well tolerated placement. The interval from diagnosis to placement (P = .001) and ability to perform spirometry (P = .002) were predictive of survival. Oximetry measurements (P = .007) and interval from diagnosis to placement (P = .02) were predictive of mortality at 6 months. CONCLUSIONS PRG is more efficacious and better tolerated than PEG, essentially because it avoids the respiratory decompensation that may occur in PEG. Therefore, PRG should be preferred in cases of ALS. Survival is linked to ALS evolution and not to the choice of PRG or PEG placement.