Comparison of liver stiffness measurements by a 2D-shear wave technique and transient elastography: results from a European prospective multi-centre study.

OBJECTIVES: To compare liver stiffness measurement (LSM) provided by Canon 2D-shear wave elastography (2D-SWE) and transient elastography (TE), the latter being the reference method. METHODS: Prospective study conducted in four European centres from 2015 to 2016 including patients with various chronic liver diseases who had LSMs with both 2D-SWE and TE on the same day. Median of 10 valid measurements (in kPa) was used for comparison using paired t test, Pearson correlation, intraclass correlation coefficient (ICC) and Bland-Altman plot. The ability of 2D-SWE to stratify patient according to recognised LSM-TE thresholds was assessed by ROC curve analysis. RESULTS: Six hundred forty patients were scanned, where 593 (92.7%), 572 (89.4%) and 537 (83.9%) had reliable LSMs by TE, 2D-SWE and both combined, respectively. In the latter (n = 537, 310 [57.7%] male, mean 55.3 ± 14.8 years), median LSM-TE and LSM-2D-SWE had a mean of 10.1 ± 9.4 kPa (range 2.4-75) and 9.1 ± 6.1 kPa (range 3.6-55.7) (paired t test: p < 0.001), respectively. These were significantly correlated (Pearson r = 0.932, p < 0.001, ICC 0.850 (0.825-0.872), bias 0.99 ± 4.33 kPa [95% limits of agreement - 9.48 to + 7.49] with proportional error towards higher LSM values). LSM-2D-SWE values significantly increased with TE categories (ANOVA: p < 0.001). AUROCs ranged from 0.935 ± 0.010 (95% CI 0.910-0.954) to 0.973 ± 0.009 (95% CI 0.955-0.985), resulting in correct classification of 390/537 (73%) patients. Three 2D-SWE measurements were sufficient for reliable LSMs. CONCLUSION: LSM using 2D-SWE correlates well with TE. It tends to underestimate higher stages of liver fibrosis but correctly classifies the majority of patients. It may be used in TE-derived algorithms to manage patients. KEY POINTS: • Liver stiffness measurement (LSM) by 2D-shear wave elastography (2D-SWE) and transient elastography (TE) are strongly correlated. • 2D-SWE shows proportionately lower LSM values compared to TE, particularly with the higher LSM range. • Three individual measurements by 2D-SWE are sufficient to assess LSM reliably.

Performance of the Attenuation Imaging Technology in the Detection of Liver Steatosis.

OBJECTIVES: The main aim was to assess the performance and cutoff value for the detection of liver steatosis (grade S > 0) with the Attenuation Imaging-Penetration (ATI-Pen) algorithm available on the Aplio i-series ultrasound systems (Canon Medical Systems, Otawara, Japan). The magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) was used as the reference standard. Secondary aims were to compare the results to those obtained with the previous ATI algorithm (Attenuation Imaging-General [ATI-Gen]) and with the controlled attenuation parameter (CAP) and to generate a regression equation between ATI-Pen and ATI-Gen values. METHODS: Consecutive adult patients potentially at risk of liver steatosis were prospectively enrolled. Each patient underwent ultrasound quantification of liver steatosis with ATI-Pen and ATI-Gen and a CAP assessment with the FibroScan system (Echosens, Paris, France). The MRI-PDFF evaluation was performed within a week. The correlations between ATI-Pen, ATI-Gen, the CAP, and the MRI-PDFF were analyzed with the Pearson rank correlation coefficient. The diagnostic performance of ATI-Pen, ATI-Gen, and the CAP was assessed with receiver operating characteristic curves and an area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: Seventy-two individuals (31 male and 41 female) were enrolled. Correlation coefficients of ATI-Pen, ATI-Gen, and the CAP with the MRI-PDFF were 0.78, 0.83, and 0.58, respectively. The AUROCs of ATI-Pen, ATI-Gen, and the CAP for detecting steatosis (S > 0) were 0.90 (95% confidence interval, 0.81-0.96), 0.92 (0.82-0.98), and 0.85 (0.74-0.92), and the cutoffs were greater than 0.69 dB/cm/MHz, greater than 0.62 dB/cm/MHz, and greater than 273 dB/m. The regression equation between ATI-Pen and ATI-Gen was ATI-Pen = 0.88 ATI-Gen + 0.13. CONCLUSIONS: Attenuation Imaging is a reliable tool for detecting liver steatosis, showing an excellent correlation with the MRI-PDFF and high performance with AUROCs of 0.90 or higher.

Drug-Drug Interactions Between Antiretrovirals and Carbamazepine/Oxcarbazepine: A Real-Life Investigation.

BACKGROUND: Carbamazepine and oxcarbazepine are potent modulators of metabolic enzymes. Hence, potential drug-drug interactions (DDIs) may occur between these 2 drugs and antiretrovirals. Here, we aimed to assess the relevance of these drug-drug interactions in real-life clinical settings. METHODS: Patients treated concomitantly with carbamazepine or oxcarbazepine and antiretrovirals for at least 3 months were considered. Data on therapeutic drug monitoring (TDM) of both antiepileptic and antiretrovirals as trough concentrations were collected. HIV-infected patients not concomitantly treated with antiepileptic drugs and who underwent TDM for antiretrovirals in the previous 2 years were considered as controls. RESULTS: Eleven HIV-positive patients prescribed carbamazepine or oxcarbazepine were identified. All the TDM evaluations for carbamazepine and oxcarbazepine that resulted were within the therapeutic ranges. TDM results of darunavir measured in these patients were comparable with values usually measured in the control group. Conversely, the trough concentrations for atazanavir and dolutegravir demonstrated significantly lower values when compared with values usually measured in HIV-infected patients not treated with antiepileptic drugs (190 ± 91 versus 546 ± 380 ng/mL; -65%, P < 0.001; 191 ± 78 versus 1096 ± 510 ng/mL; -83%, P < 0.001, respectively). CONCLUSIONS: Co-administration of carbamazepine or oxcarbazepine with atazanavir or dolutegravir should be avoided owing to the potential risk of virological failure; in case of these 2 drugs, the adoption of TDM is strongly advisable, eventually combining with increased antiretroviral doses.

Assessment of biopsy-proven liver fibrosis by two-dimensional shear wave elastography: An individual patient data-based meta-analysis.

Two-dimensional shear wave elastography (2D-SWE) has proven to be efficient for the evaluation of liver fibrosis in small to moderate-sized clinical trials. We aimed at running a larger-scale meta-analysis of individual data. Centers which have worked with Aixplorer ultrasound equipment were contacted to share their data. Retrospective statistical analysis used direct and paired receiver operating characteristic and area under the receiver operating characteristic curve (AUROC) analyses, accounting for random effects. Data on both 2D-SWE and liver biopsy were available for 1,134 patients from 13 sites, as well as on successful transient elastography in 665 patients. Most patients had chronic hepatitis C (n = 379), hepatitis B (n = 400), or nonalcoholic fatty liver disease (n = 156). AUROCs of 2D-SWE in patients with hepatitis C, hepatitis B, and nonalcoholic fatty liver disease were 86.3%, 90.6%, and 85.5% for diagnosing significant fibrosis and 92.9%, 95.5%, and 91.7% for diagnosing cirrhosis, respectively. The AUROC of 2D-SWE was 0.022-0.084 (95% confidence interval) larger than the AUROC of transient elastography for diagnosing significant fibrosis (P = 0.001) and 0.003-0.034 for diagnosing cirrhosis (P = 0.022) in all patients. This difference was strongest in hepatitis B patients. CONCLUSION: 2D-SWE has good to excellent performance for the noninvasive staging of liver fibrosis in patients with hepatitis B; further prospective studies are needed for head-to-head comparison between 2D-SWE and other imaging modalities to establish disease-specific appropriate cutoff points for assessment of fibrosis stage. (Hepatology 2018;67:260-272).

Drug-induced liver steatosis in patients with HIV infection.

Drug-induced liver injury (DILI) due to the use of prescription and non-prescription medication by HIV-positive and HIV-negative patients is one of the main causes of acute liver failure and transplantation in Western countries and, although rare, has to be considered a serious problem because of its unforeseeable nature and possibly fatal course. Drug-induced steatosis (DIS) and steatohepatitis (DISH) are infrequent but well-documented types of DILI. Although a number of commonly used drugs are associated with steatosis, it is not always easy to identify them as causative agents because of the weak temporal relationship between the administration of the drug and the clinical event, the lack of a confirmatory re-challenge, and the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population, which often makes it difficult to make a differential diagnosis of DIS and DISH. The scenario is even more complex in HIV-positive patients not only because of the underlying disease, but also because the various anti-retroviral regimens have different effects on liver steatosis. Given the high prevalence of liver steatosis in HIV-positive patients and the increasing use of drugs associated with a potential steatotic risk, the identification of clinical signs suggesting liver damage should help to avoid the possible misdiagnosis of "primary" NAFLD in a patient with DIS or DISH. This review will therefore initially concentrate on the current diagnostic criteria for DIS/DISH and their differential diagnosis from NAFLD. Subsequently, it will consider the different clinical manifestations of iatrogenic liver steatosis in detail, with specific reference to HIV-positive patients. Finally, the last part of the review will be dedicated to the possible effects of liver steatosis on the bioavailability of antiretroviral and other drugs.

Evaluation of Inter-System Variability in Liver Stiffness Measurements.

AIM: The primary aim of this study was to determine the inter-system variability of liver stiffness measurements (LSMs) in patients with varying degrees of liver stiffness. The secondary aim was to determine the inter-observer variability of measurements. MATERIALS AND METHODS: 21 individuals affected by chronic hepatitis C and 5 healthy individuals were prospectively enrolled. The assessment of LSMs was performed using six ultrasound (US) systems, four of which with point shear wave elastography (p-SWE) and two with 2 D shear wave elastography (2D-SWE) systems. The Fibroscan (Echosens, France) was used as the reference standard. Four observers performed the measurements in pairs (A-B, C-D). The agreement between different observers or methods was calculated using Lin's concordance correlation coefficient. The Bland-Altman limits of agreement (LOA) were calculated as well. RESULTS: There was agreement above 0.80 for all pairs of systems. The mean difference between the values of the systems with 2D-SWE technique was 1.54 kPa, whereas the maximum mean difference between the values of three out of four systems with the pSWE technique was 0.79 kPa. The intra-patient concordance for all systems was 0.89 (95 % CI: 0.83 - 0.94). Inter-observer agreement was 0.96 (95 % CI: 0.94 - 0.98) for the pair of observers A-B and 0.93 (95 % CI: 0.89 - 0.96) for the pair of observers C-D. CONCLUSION: The results of this study show that the agreement between LSMs performed with different US systems is good to excellent and the overall inter-observer agreement in "ideal conditions" is above 0.90 in expert hands.

Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.

BACKGROUND & AIMS: The prevalence of fatty liver underscores the need for non-invasive characterization of steatosis, such as the ultrasound based controlled attenuation parameter (CAP). Despite good diagnostic accuracy, clinical use of CAP is limited due to uncertainty regarding optimal cut-offs and the influence of covariates. We therefore conducted an individual patient data meta-analysis. METHODS: A review of the literature identified studies containing histology verified CAP data (M probe, vibration controlled transient elastography with FibroScan®) for grading of steatosis (S0-S3). Receiver operating characteristic analysis after correcting for center effects was used as well as mixed models to test the impact of covariates on CAP. The primary outcome was establishing CAP cut-offs for distinguishing steatosis grades. RESULTS: Data from 19/21 eligible papers were provided, comprising 3830/3968 (97%) of patients. Considering data overlap and exclusion criteria, 2735 patients were included in the final analysis (37% hepatitis B, 36% hepatitis C, 20% NAFLD/NASH, 7% other). Steatosis distribution was 51%/27%/16%/6% for S0/S1/S2/S3. CAP values in dB/m (95% CI) were influenced by several covariates with an estimated shift of 10 (4.5-17) for NAFLD/NASH patients, 10 (3.5-16) for diabetics and 4.4 (3.8-5.0) per BMI unit. Areas under the curves were 0.823 (0.809-0.837) and 0.865 (0.850-0.880) respectively. Optimal cut-offs were 248 (237-261) and 268 (257-284) for those above S0 and S1 respectively. CONCLUSIONS: CAP provides a standardized non-invasive measure of hepatic steatosis. Prevalence, etiology, diabetes, and BMI deserve consideration when interpreting CAP. Longitudinal data are needed to demonstrate how CAP relates to clinical outcomes. LAY SUMMARY: There is an increase in fatty liver for patients with chronic liver disease, linked to the epidemic of the obesity. Invasive liver biopsies are considered the best means of diagnosing fatty liver. The ultrasound based controlled attenuation parameter (CAP) can be used instead, but factors such as the underlying disease, BMI and diabetes must be taken into account. Registration: Prospero CRD42015027238.

Noninvasive assessment of liver steatosis in children: the clinical value of controlled attenuation parameter.

BACKGROUND: To assess the clinical validity of controlled attenuation parameter (CAP) in the diagnosis of hepatic steatosis in a series of overweight or obese children by using the imperfect gold standard methodology. METHODS: Consecutive children referred to our institution for auxological evaluation or obesity or minor elective surgery were prospectively enrolled. Anthropometric and biochemical parameters were recorded. Ultrasound (US) assessment of steatosis was carried out using ultrasound systems. CAP was obtained with the FibroScan 502 Touch device (Echosens, Paris, France). Pearson's or Spearman's rank correlation coefficient were used to test the association between two study variables. Optimal cutoff of CAP for detecting steatosis was 249 dB/m. The diagnostic performance of dichotomized CAP, US, body mass indexes (BMI), fatty liver index (FLI) and hepatic steatosis index (HSI) was analyzed using the imperfect gold standard methodology. RESULTS: Three hundred five pediatric patients were enrolled. The data of both US and CAP were available for 289 children. Steatosis was detected in 50/289 (17.3%) children by US and in 77/289 (26.6%) by CAP. A moderate to good correlation was detected between CAP and BMI (r = 0.53), FLI (r = 0.55) and HSI (r = 0.56). In obese children a moderate to good correlation between CAP and insulin levels (r = 0.54) and HOMA-IR (r = 0.54) was also found. Dichotomized CAP showed a performance of 0.70 (sensitivity, 0.72 [0.64-0.79]; specificity, 0.98 [0.97-0.98], which was better than that of US (performance, 0.37; sensitivity, 0.46 [0.42-0.50]; specificity, 0.91 [0.89-0.92]), BMI (performance, 0.22; sensitivity, 0.75 [0.73-0.77]; specificity, 0.57 [0.55-0.60]) and FLI or HSI. CONCLUSIONS: For the evaluation of liver steatosis in children CAP performs better than US, which is the most widely used imaging technique for screening patients with a suspicion of liver steatosis. A cutoff value of CAP of 249 dB/m rules in liver steatosis with a very high specificity.

Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection.

OBJECTIVE: Sialic-acid-binding immunoglobulin-like lectin-7 (Siglec-7) is a natural killer (NK) cell inhibitory receptor associated with NK phenotypic and functional abnormalities in HIV-1 infection. We investigated the significance of NK-expressed and serum soluble Siglec-7 in relation to NK functional ability and parameters of liver necroinflammation and fibrosis in chronic HCV infection. DESIGN: NK-expressed and serum Siglec-7 were evaluated in 130 and 166 HCV-infected individuals by flow cytometry and ELISA, respectively. NK cell degranulation and cytokine secretion were determined by flow cytometry. 65 patients with chronic HBV infection, 84 with chronic biliary disorders and 168 healthy donors served as controls. RESULTS: Expression of Siglec-7 was significantly decreased on NK cells from HCV-infected and HBV-infected patients and, conversely, serum Siglec-7 was significantly increased in these patients compared with controls. The frequency of Siglec-7pos NK cells was significantly higher at baseline in sustained virological responders to pegylated interferon-α/ribavirin treatment than in non-responders. Activating receptor expression was significantly higher in Siglec-7pos NK cells and was associated with increased degranulation and cytokine secretion compared with Siglec-7neg cells. In chronic HCV infection, there was an inverse correlation between Siglec-7 expression and serum aminotransferases, γ-glutamyl transpeptidase, liver stiffness, aspartate aminotransferase to platelet ratio index and fibrosis-4 scores, and a positive correlation between serum Siglec-7 and the same clinical parameters, including histological staging. CONCLUSIONS: These findings identify Siglec-7neg NK cells as a dysfunctional subpopulation associated with severe liver disease in chronic HCV infection.

The clinical value of controlled attenuation parameter for the noninvasive assessment of liver steatosis.

BACKGROUND & AIMS: Ultrasound is the imaging modality most widely utilized in the general population for diagnostic purposes. Controlled attenuation parameter is a novel noninvasive method for assessing steatosis. Our aim was to investigate whether the clinical value of controlled attenuation parameter in patients referred for abdominal ultrasound examinations is affected by liver fibrosis. METHODS: Consecutive patients referred for abdominal ultrasound examinations were enrolled. Controlled attenuation parameter and liver stiffness were assessed with the FibroScan (Echosens, France). Liver fibrosis was staged according to published cutoffs of liver stiffness measurements. Pearson's or Spearman's rank correlation coefficient was used to test the association between two study variables. Optimal cutoff of controlled attenuation parameter for diagnosing liver steatosis (S≥2) was 256 dB/m. The diagnostic performance and accuracy of dichotomized controlled attenuation parameter, ultrasound and body mass index were analysed using the imperfect gold standard methodology. RESULTS: A total of 726 subjects (464 males and 262 females) were studied. Five hundred and eight-nine (81.1%) patients were affected by chronic viral hepatitis. Correlation of controlled attenuation parameter with ultrasound score was 0.48 and 0.57 in patients with and without chronic viral hepatitis respectively. In patients with chronic viral hepatitis, ultrasound, dichotomized controlled attenuation parameter and body mass index showed performance of 58.2%, 82.3% and 46.7%, respectively, whereas in patients without chronic viral hepatitis, the performance was 86.4%, 68.6% and 48.6% respectively. CONCLUSIONS: In patients with chronic viral hepatitis and advanced liver fibrosis, controlled attenuation parameter performs better than ultrasound for assessing liver steatosis, whereas in patients without viral hepatitis and with nonsignificant liver disease ultrasound shows the best performance.

Liver stiffness assessed by transient elastography in patients with ß thalassaemia major.

RATIONALE FOR THE STUDY: This cross-sectional multicenter study was conducted to investigate any difference in liver stiffness measurements (LSM), evaluated by transient elastography, between patients affected by ß thalassaemia major, with and without hepatitis C virus (HCV) infection, and healthy blood donors (controls). Secondary aim was to assess any correlation between transient elastography and serum ferritin, liver magnetic resonance imaging (MRI) T2* or superconductive quantum interference device (SQUID) liver susceptometry values. MATERIALS AND METHODS: The study involved three centers. Transient elastography and MRI T2* examinations were performed in all centers. SQUID liver susceptometry was performed in center1 and center2. T-test for independent data or Mann-Whitney U test was used to analyse differences between two groups. Univariate Pearson's r coefficient was used to test correlations between liver stiffness measurements and all other variables. RESULTS: In a study with 119 patients and 183 controls, patients who had never been infected with HCV showed significantly higher LSMs than controls [5.7 (95% CI, 5.2-6.2) kPa vs. 4.3 (95% CI, 4.1-4.4) kPa, p < 0.0001]. A moderate correlation between LSMs and ferritin values, adjusted for gender and age, was found in patients (r = 0.49, p < 0.0001) but not in controls (r = -0.22, p = 0.6). No correlation between LSMs and MRI T2* or SQUID liver susceptometry values was observed. In conclusion, compared to controls ß thalassaemia major patients had a significant increase in LSMs independently from HCV infection.

Ultrasound point shear wave elastography assessment of liver and spleen stiffness: effect of training on repeatability of measurements.

OBJECTIVES: To evaluate reproducibility of measurements of spleen stiffness (SS) and liver stiffness (LS) at several sites by using point shear wave elastography (pSWE) and to investigate any training effect. METHODS: Healthy volunteers were consecutively enrolled. Measurements of SS and LS were performed by an expert (observer 1) and a novice (observer 2) at three different sites of liver and spleen. To assess the effect of training the study was conducted in two periods (period 1 and period 2). Concordance correlation coefficient was used to assess intra-observer and inter-observer reproducibility. RESULTS: A total of 92 subjects (67 men and 25 women) were enrolled in the study. Both intra-observer and inter-observer agreement were higher for the liver than for the spleen. Overall, the highest intra-observer and inter-observer agreement were obtained for the assessment of LS through intercostal space, and for measurements at this site there was a significantly better performance of observer 2 after the training period. For both observers, training improved the repeatability of SS measurements at all sites. A good intra-observer agreement was obtained only for measurements at the spleen lower pole. CONCLUSIONS: The results of this study show that a learning curve in pSWE acquisition should be taken into account both for SS and LS measurements. KEY POINTS: Reproducibility of SS measurements depends on the expertise of the operator. To achieve good reproducibility between measurements a training period is required. A learning curve in pSWE acquisition should be taken into account. SS measurements are less reproducible than LS measurements.

Shear wave elastography for evaluation of liver fibrosis.

The prognosis and management of chronic viral hepatitis mainly depend on the extent of liver fibrosis, particularly in chronic hepatitis C. Liver histologic analysis is still considered the reference standard in the assessment of liver fibrosis despite the interobserver and interobserver variability in staging and some morbidity and mortality risks. Thus, noninvasive methods for assessing liver fibrosis are of great clinical interest. In the last decade, ultrasound-based techniques to estimate the stage of liver fibrosis have become commercially available. They all have the capability to noninvasively evaluate differences in the elastic properties of soft tissues by measuring tissue behavior when a mechanical stress is applied. Shear wave elastography relies on the generation of shear waves determined by the displacement of tissues induced by the force of a focused ultrasound beam or by an external push. This article reviews the results that have been obtained with shear wave elastography for assessment of liver fibrosis.

Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study.

UNLABELLED: Real-time shear wave elastography (SWE) is a novel, noninvasive method to assess liver fibrosis by measuring liver stiffness. This single-center study was conducted to assess the accuracy of SWE in patients with chronic hepatitis C (CHC), in comparison with transient elastography (TE), by using liver biopsy (LB) as the reference standard. Consecutive patients with CHC scheduled for LB by referring physicians were studied. One hundred and twenty-one patients met inclusion criteria. On the same day, real-time SWE using the ultrasound (US) system, Aixplorer (SuperSonic Imagine S.A., Aix-en-Provence, France), TE using FibroScan (Echosens, Paris, France), and US-assisted LB were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic (ROC) curve were performed to calculate optimal area under the ROC curve (AUROC) for F0-F1 versus F2-F4, F0- F2 versus F3-F4, and F0-F3 versus F4 for both real-time SWE and TE. Liver stiffness values increased in parallel with degree of liver fibrosis, both with SWE and TE. AUROCs were 0.92 (95% confidence interval [CI]: 0.85-0.96) for SWE and 0.84 (95% CI: 0.76-0.90) for TE (P = 0.002), 0.98 (95% CI: 0.94-1.00) for SWE and 0.96 (95% CI: 0.90-0.99) for TE (P = 0.14), and 0.98 (95% CI: 0.93-1.00) for SWE and 0.96 (95% CI: 0.91-0.99) for TE (P = 0.48), when comparing F0-F1 versus F2- F4, F0- F2 versus F3-F4, and F0 -F3 versus F4, respectively. CONCLUSION: The results of this study show that real-time SWE is more accurate than TE in assessing significant fibrosis (≥ F2). With respect to TE, SWE has the advantage of imaging liver stiffness in real time while guided by a B-mode image. Thus, the region of measurement can be guided with both anatomical and tissue stiffness information.

Toward acquisition protocol standardization for estimating liver fat content using ultrasound attenuation coefficient imaging.

PURPOSE: This study's primary aim was to assess factors affecting ultrasound attenuation coefficient (AC) measurement repeatability using the Canon ultrasound (US) system. The secondary aim was to evaluate whether similar results were obtained with other vendors' AC algorithms. METHODS: This prospective study was performed at two centers from February to November 2022. AC was obtained using two US systems (Aplio i800 of Canon Medical Systems and Arietta 850 of Fujifilm). An algorithm combining AC and the backscatter coefficient was also used (Sequoia US System, Siemens Healthineers). To evaluate inter-observer concordance, AC was obtained by two expert operators using different transducer positions with regions of interest (ROIs) varying in terms of depth and size. Intra-observer concordance was evaluated on measurements performed intercostally, subcostally, and in the left liver lobe. Lin's concordance correlation coefficient was used. RESULTS: Thirty-four participants (mean age, 49.4±15.1 years; 18 females) were studied. AC values progressively decreased with depth. The measurements in intercostal spaces on bestquality US images using a 3-cm ROI with its upper edge 2 cm below the liver capsule during breath-hold showed the highest intra-observer and inter-observer concordance (0.92 [95% confidence interval, 0.88 to 0.95] and 0.89 [0.82 to 0.96], respectively). Measurements in the left lobe showed the lowest intra-observer and inter-observer concordance (0.67 [0.43 to 0.90] and 0.58 [0.12 to 1.00], respectively). Intercostal space measurements also had the highest repeatability for the other two ultrasound systems. CONCLUSION: AC values obtained in intercostal spaces on best-quality images using a 3-cm ROI placed with its top 2 cm below the liver capsule were highly repeatable.

Performance of real-time strain elastography, transient elastography, and aspartate-to-platelet ratio index in the assessment of fibrosis in chronic hepatitis C.

OBJECTIVE: The purpose of this article is to evaluate the diagnostic performance of transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index in assessing fibrosis in patients with chronic hepatitis C by using histologic Metavir scores as reference standard. SUBJECTS AND METHODS: Consecutive patients with chronic hepatitis C scheduled for liver biopsy were enrolled. Liver biopsy was performed on the same day as transient elastography and real-time strain elastography. Transient elastography and real-time strain elastography were performed in the same patient encounter by a single investigator using a medical device based on elastometry and an ultrasound machine, respectively. Diagnostic performance was assessed by using receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) analysis. RESULTS: One hundred thirty patients (91 men and 39 women) were analyzed. The cutoff values for transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index were 6.9 kPa, 1.82, and 0.37, respectively, for fibrosis score of 2 or higher; 7.3 kPa, 1.86, and 0.70, respectively, for fibrosis score of 3 or higher; and 9.3 kPa, 2.33, and 0.70, respectively, for fibrosis score of 4. AUC values of transient elastography, real-time strain elastography, aspartate-to-platelet ratio index were 0.88, 0.74, and 0.86, respectively, for fibrosis score of 2 or higher; 0.95, 0.80, and 0.89, respectively, for fibrosis score of 3 or higher; and 0.97, 0.80, and 0.84, respectively, for fibrosis score of 4. A combination of the three methods, when two of three were in agreement, showed AUC curves of 0.93, 0.95, and 0.95 for fibrosis scores of 2 or higher, 3 or higher, and 4, respectively. CONCLUSION: Transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index values were correlated with histologic stages of fibrosis. Transient elastography offered excellent diagnostic performance in assessing severe fibrosis and cirrhosis. Real-time elastography does not yet have the potential to substitute for transient elastography in the assessment of liver fibrosis.

Serum cytokine profile by ELISA in patients with echinococcal cysts of the liver: a stage-specific approach to assess their biological activity.

To investigate the usefulness of serum cytokine dosage in the clinical management of cystic echinococcosis (CE), we analyzed serum levels of Th1 and Th2 cytokines in patients with hepatic CE in different cyst stages, CE1-2 (active), CE3a-3b (transitional), and CE4-5 (inactive). Ex vivo assessment of Th1 (IFN-γ) and Th2 (IL-4, IL-13, and IL-10) cytokines in sera was carried out using ELISA. IL-10 was undetectable in all serum samples of patients and controls, while a few sera contained measurable amounts of IFN-γ, IL-4, and IL-13. No statistically significant difference was found between the percentages of positive samples for each cytokine and the different groups analyzed (patients/controls, stage, number, location, and size of the cyst, serology, and sex of patients), with the exception of the association of IL-4 and IL-13 with the cyst stage. Overall, this investigation showed many limits of serum cytokine dosage as a marker of biological activity of echinococcal cysts. Because of low sensitivity and lack of specificity of this test, we believe that other ways to evaluate ex vivo biological activity of the cysts should be explored.

Quantification of Liver Fat Content with the iATT Algorithm: Correlation with Controlled Attenuation Parameter.

Background: The primary aim of our study was to assess the correlation between an improved version of the attenuation coefficient available on the Arietta 850 ultrasound system (iATT, Fujifilm Healthcare, Tokyo, Japan) and controlled attenuation parameter (CAP). The secondary aim was to assess whether focusing only on iATT acquisition without following the strict protocol for liver stiffness measurements would affect iATT measurement. Methods: Consecutive individuals were enrolled. Pearson's r was used to test the correlation between ATT and CAP values. The concordance between iATT and CAP was tested using Lin's concordance correlation coefficient (CCC). Results: 354 individuals (203 males, 151 females) were studied. The overall Pearson correlation between CAP and iATT values obtained following or not following the liver stiffness measurement protocol, respectively, were r = 0.73 and r = 0.71. The correlation was affected by the interquartile range/median (IQR/M) of the 10 measurements: it was r = 0.75 for IQR/M ≤ 15% and r = 0.60 for IQR/M > 15%. CCC showed that there was a moderate to good concordance between iATT and CAP values. Conclusion: iATT shows a strong correlation with CAP that does not decrease when the protocol for liver stiffness acquisition is not followed. The correlation between iATT and CAP values is higher when the IQR/M ≤ 15%.