OBJECTIVE: Liver transient elastography (TE) has been endorsed by the WHO as the first-line diagnostic tool for liver diseases. Although unreliable and invalid results caused by intercostal space (ICS)-associated factors (including excessive subcutaneous fat and a narrow ICS relative to the transducer size) and operator inexperience are not uncommon, no standard guidelines for ideal probe placement are currently available. Herein, we conducted a prospective observational study to identify an ideal measurement site and respiratory condition for TE by characterizing anatomical and biomechanical properties of the ICSs using ultrasound B-mode and elasticity imaging.
METHODS: Intercostal ultrasound was performed pointwise at four specific sites in 59 patients to simultaneously measure the width, stiffness, and skin‒liver capsule distance (SCD) of the ICSs over the liver, under end-inspiratory and end-expiratory conditions. Intersections between the 8th ICS and anterior axillary line, the 7th ICS and anterior axillary line, the 8th ICS and mid-axillary line, and the 7th ICS and mid-axillary line were defined as Sites 1 to 4, respectively.
RESULTS: Results indicated that Sites 2 and 3 presented greater intercostal width; Sites 3 and 4 displayed lower intercostal stiffness; Sites 2 and 3 exhibited a shorter SCD. The ICSs were significantly wider and stiffer at end-inspiration. Additionally, the liver was more easily visualized at Sites 1 and 3.
CONCLUSIONS: We recommend Site 3 for TE probe placement owing to its greater width, lower stiffness, and smaller abdominal wall thickness. Performing TE at end-inspiration is preferred to minimize transducer-rib interferences. This study paves the way toward a standardized TE examination procedure.
UNASSIGNED: A standardized measurement protocol for WHO-recommended liver TE was first established to improve the success and efficiency of the examination procedure.
CONCLUSIONS: WHO-recommended TE is unreliable or fails due to intercostal space-related factors. The 8th intercostal space on the mid-axillary line and end-inspiration are recommended. This standardized protocol aids in handling challenging cases and simplifies operational procedures.

Transient elastography (TE), recommended by the WHO, is an established method for characterizing liver fibrosis via liver stiffness measurement (LSM). However, technical barriers remain towards point-of-care application, as conventional TE requires wired connections, possesses a bulky size, and lacks adequate imaging guidance for precise liver localization. In this work, we report the design, phantom validation, and clinical evaluation of a palm-sized TE system that enables simultaneous B-mode imaging and LSM. The performance of this system was validated experimentally using tissue-equivalent reference phantoms (1.45-75 kPa). Comparative studies against other liver elastography techniques, including conventional TE and two-dimensional shear wave elastography (2D-SWE), were performed to evaluate its reliability and validity in adults with various chronic liver diseases. Intra- and inter-operator reliability of LSM were established by an elastography expert and a novice. A good agreement was observed between the Young\'s modulus reported by the phantom manufacturer and this system (bias: 1.1-8.6%). Among 121 patients, liver stiffness measured by this system and conventional TE were highly correlated (r = 0.975) and strongly agreed with each other (mean difference: -0.77 kPa). Inter-correlation of this system with conventional TE and 2D-SWE was observed. Excellent-to-good operator reliability was demonstrated in 60 patients (ICCs: 0.824-0.913). We demonstrated the feasibility of employing a fully integrated phased array probe for reliable and valid LSM, guided by real-time B-mode imaging of liver anatomy. This system represents the first technical advancement toward point-of-care liver fibrosis assessment. Its small footprint, along with B-mode guidance capability, improves examination efficiency and scales up screening for liver fibrosis.

Liver diseases of various etiologies are becoming increasingly common in the pediatric population. So far, the gold diagnostic standard in these disorders is liver biopsy. This procedure is invasive, painful and requires general anesthesia in this group of patients. Due to the continuous development of new research techniques, such as liver elastography, it is necessary to evaluate them in the context of their diagnostic usefulness. Ultrasound elastography, as a quick and effective method, is being used more and more often in the assessment and monitoring of liver dysfunction in both adults and children. There are several techniques of liver elastography, such as transient elastography, shear wave elastography consisting of various subtypes such as two-dimensional shear wave elastography, acoustic radiation force impulse and point shear wave elastography, which differ in terms of the measurement technique and the achieved results. The purpose of our review was to determine whether techniques of liver elastography could replace liver biopsy. Although now, based on the analyzed papers, elastography cannot replace liver biopsy, in our opinion, the role of this tool in monitoring pediatric patients with liver diseases will grow in the coming years.

OBJECTIVE: Patients with cirrhosis secondary to chronic hepatitis C virus (HCV) are at risk for hepatocellular carcinoma (HCC) despite a sustained virological response (SVR). We examined whether post-SVR liver stiffness measurement (LSM) could be used to stratify HCC risk.
METHODS: This was a retrospective cohort study of 1850 participants identified from the Veterans Health Administration, with HCV cirrhosis and SVR, followed up over 5099 person-years, from the time of post-SVR elastography until death, HCC, or the end of the study.
RESULTS: The risk of HCC increased by 3% with every 1-kPa increase in LSM (adjusted hazard ratio [aHR], 1.03, 95% confidence interval [CI], 1.01-1.04; P < .001) and decreased with the number of years from SVR (aHR, 0.79; 95% CI, 0.70-0.90; P = .0003). The adjusted annual risk of HCC was 2.03% among participants with post-SVR LSM <10 kPa, 2.48% in LSM 10-14.9 kPa (aHR, 1.71; 95% CI, 1.01-2.88; P = .046), 3.22% for LSM 15-19.9 kPa (aHR, 1.59; 95% CI, 0.78-3.20; P = .20), 5.07% among LSM 20-24.9 kPa (aHR, 2.55; 95% CI, 1.30-5.01; P = .01), and 5.44% in LSM ≥25 kPa (aHR, 3.03; 95% CI, 1.74-5.26; P < .0001). The adjusted annual risk of HCC was < 0.4% in participants with LSM <5 kPa and without diabetes mellitus.
CONCLUSIONS: LSM predicts rates of HCC in patients with HCV cirrhosis after SVR at multiple cutoff levels and offers a single test to predict portal hypertension-related complications and HCC. Patients with LSM <5 kPa in the absence of diabetes mellitus had a low risk of HCC in which surveillance could be discontinued.

UNASSIGNED: Liver stiffness measurements can be used to assess liver fibrosis and can be acquired by transient elastography using FibroScan® and with Acoustic Radiation Force Impulse imaging. The study aimed to establish liver stiffness measurement scores using FibroScan® and Acoustic Radiation Force Impulse in a chronic hepatitis C cohort and to explore the correlation and agreement between the scores and the factors influencing agreement.
UNASSIGNED: Patients had liver stiffness measurements acquired with FibroScan® (right lobe of liver) and Acoustic Radiation Force Impulse (right and left lobe of liver). We used Spearman\'s correlation to explore the relationship between FibroScan® and Acoustic Radiation Force Impulse scores. A Bland-Altman plot was used to evaluate bias between the mean percentage differences of FibroScan® and Acoustic Radiation Force Impulse scores. Univariable and multivariable analyses were used to assess how factors such as body mass index, age and gender influenced the agreement between liver stiffness measurements.
UNASSIGNED: Bland-Altman showed the average (95% CI) percentage difference between FibroScan® and Acoustic Radiation Force Impulse scores was 27.5% (17.8, 37.2), p  < 0.001. There was a negative correlation between the average and percentage difference of the FibroScan® and Acoustic Radiation Force Impulse scores ( r (95% CI) = -0.41 (-0.57, -0.21), p < 0.001), thus showing that percentage difference gets smaller for greater FibroScan® and Acoustic Radiation Force Impulse scores. Body mass index was the biggest influencing factor on differences between FibroScan® and Acoustic Radiation Force Impulse (r = 0.12 (0.01, 0.23), p = 0.05). Acoustic Radiation Force Impulse scores at segment 5/8 and the left lobe showed good correlation (r (95% CI) = 0.83 (0.75, 0.89), p < 0.001).
UNASSIGNED: FibroScan® and Acoustic Radiation Force Impulse had similar predictive values for the assessment of liver stiffness in patients with chronic hepatitis C infection; however, the level of agreement varied across lower and higher scores.

BACKGROUND: Variceal haemorrhage is a life-threatening complication that occurs in up to 40% of patients with chronic liver disease including cirrhosis. It is associated with a mortality rate of 20% with each episode of variceal bleeding. Esophagogastroduodenoscopy is the gold standard for the detection of esophageal varices but is an invasive procedure and not very cost-effective. Our study was designed to correlate the presence of esophageal varices on endoscopy with the liver stiffness measurement using liver elastography in patients with chronic liver disease. We also compared various non-invasive predictors like laboratory parameters and ultrasound features and correlated them with the presence of varices in patients with chronic liver disease.
METHODS: This prospective observational study was conducted in a tertiary-care hospital in South India from November 2017 to April 2019. All patients with chronic liver disease were subjected to endoscopy, and the presence of esophageal varices and their grading was noted. The predictive efficacy of ultrasound elastography using Toshiba Aplio 500 ultrasound two-dimensional shear wave elastography (2D-SWE) in predicting esophageal varices was calculated and compared with the efficacy of predicting esophageal varices by other non-invasive parameters like laboratory investigations, abdominal ultrasound, and liver scores like Child-Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD) score, fibrosis 4 (FIB-4) score, aspartate aminotransferase-to-platelet ratio index (APRI) score, and aspartate aminotransferase/alanine aminotransferase ratio (AAR).
RESULTS: The study included a total of 168 patients out of which 57% (96 patients) had no varices. About 52 patients (72.2%) had F1/Grade I varices, 9 (12.5%) had F2/Grade II varices, and 11 (15.3%) had F3/Grade III varices. The greatest predictive value for esophageal varices was liver stiffness with a diagnostic accuracy of 81.7%. Ultrasound features like coarse echotexture of the liver (66.7%), splenomegaly (67%), dilated portal vein (78.6%), and presence of moderate ascites (66.7%) had a significant statistical association with the presence of esophageal varices. Laboratory parameters like thrombocytopenia of less than 1.5 lakhs/cu.mm (52.8%), albumin <3 g/dL (60.4%), and reversal of albumin/globulin ratio (52.4%) were significant predictors of esophageal varices. The odds ratio for significant scores in predicting oesophageal varices using binary logistic regression was significant in patients whose liver elastography grade was more than F4, CTP score was B, MELD score was >11, and FIB-4 scores was >3.25 and between 1.46 and 3.25.
CONCLUSIONS: Liver elastography is a non-invasive procedure that can be a useful tool in predicting esophageal varices in chronic liver disease. Other non-invasive predictors like ultrasound abdomen and laboratory parameters can also be considered a replacement for repeated invasive endoscopy, thus facilitating early intervention and avoiding unfavourable outcomes in patients with chronic liver disease.

The agreement of elastography techniques in chronic Hepatitis B (CHB) needs evaluation. We aimed to evaluate, in CHB, the agreement between transient elastography (TE) and two-dimensional shear wave elastography (2D-SWE), analyzing the factors related to the disagreement of measures.
CHB patients underwent liver stiffness measures with both TE and 2D-SWE on the same day. For concordance analysis, we defined liver fibrosis as F0/1 vs. F ≥ 2, F0/1-F2 vs. F ≥ 3 and F0/1-F2-F3 vs. F4 for both methods. Logistic regression analysis was used to identify the variables independently associated with the disagreement between methods.
A total of 150 patients were enrolled. Liver fibrosis categorization according to TE was: F0-F1 = 73 (50.4%), F ≥ 2 = 40 (27.6%), F ≥ 3 = 21 (14.5%) and F4 = 11 (7.6%), and according to 2D-SWE was: F0/F1 = 113 (77.9%), F ≥ 2 = 32 (22.1%), F≥ 3 = 25 (17.2%) and F4 = 11 (7.6%). It was observed that 20.0% of the sample had steatosis (CAP≥ 275 dB/m). TE and SD-SWE estimated equal fibrosis stages in 79.3% of cases. Spearman\'s correlation coefficient was 0.71 (p < 0.01). Kappa values for F ≥ 2, F ≥ 3 and F = 4 were: 0.78, p < 0.001; 0.73, p < 0.001; and 0.64, p < 0.001, respectively. Diabetes mellitus (DM) (OR 5.04; 95%CI: 1.89-13.3; p < 0.001) and antiviral treatment (OR 6.79; 95%CI: 2.33-19.83; p < 0.001) were independently associated with discordance between both methods.
In CHB, there is strong correlation and good agreement between TE and 2D-SWE in identifying fibrosis stages. Diabetes mellitus and antiviral therapy may impact the agreement of stiffness measures obtained with these elastographic methods.

Background and Objectives: Diabetes mellitus (DM) is connected to both cardiovascular disease and non-alcoholic fatty liver disease (NAFLD), and is an important component of metabolic syndrome (MetS). NAFLD can be detected and quantified using the vibration controlled transient elastography (VCTE) and the controlled attenuation parameter (CAP), whereas traditional and two-dimensional speckle tracking echocardiography (2D-STE) can reveal subclinical abnormalities in heart function. We sought to see if there was a link between left cardiac dysfunction and different levels of hepatic fibrosis in MetS patients with DM and NAFLD. Patients and Methods: We recruited successive adult subjects with MetS and a normal left ventricular ejection fraction, who were divided into two groups according to the presence or absence of DM. The presence of NAFLD was established by CAP and VCTE, while conventional and 2D-STE were used to assess left heart\'s systolic and diastolic function. The mean age of the MetS subjects was 62 ± 10 years, 82 (55%) were men. The distribution of liver steatosis severity was similar among diabetics and non-diabetics, while liver fibrosis grade 2 and 3 was significantly more frequent in diabetics (p = 0.02, respectively p = 0.001). LV diastolic dysfunction was found in 52% of diabetic and in 36% of non-diabetic MetS patients (p = 0.04). 2D-STE identified in the diabetic subjects increased LA stiffness (40% versus 24%, p = 0.03) and reduced global left ventricular longitudinal strain (47% versus 16%, p < 0.0001). Liver fibrosis grade ≥ 2 was identified as an independent predictor of both subclinical LV systolic dysfunction and of LA dysfunction in MetS patients with DM (p < 0.0001). Conclusions: The current investigation confirms the link between liver stiffness and subclinical cardiac dysfunction as detected by 2D-STE in MetS patients with DM. The novel parameters derived from LA and LV 2D-STE have demonstrated greater sensitivity compared to the older measurements, and a substantial connection with hepatic fibrosis.

To explore the clinical application of shear wave elastography (SWE) in evaluating the degree of liver fibrosis in children.
To explore the value of SWE in assessing liver fibrosis in children, the correlation between elastography values and the METAVIR grade of liver fibrosis in children with biliary system or liver diseases was studied. Children with significant liver enlargement were enrolled, and the fibrosis grade was analyzed to explore the value of SWE in assessing the degree of liver fibrosis in the presence of significant liver enlargement.
A total of 160 children with bile system or liver diseases were recruited. The areas under the receiver operating characteristic curve (AUROCs) for liver biopsy from stage F1 to F4 were 0.990, 0.923, 0.819, and 0.884. According to the degree of liver fibrosis at liver biopsy, there was a high correlation between the SWE value and the degree of liver fibrosis (correlation coefficient 0.74). There was no significant correlation between the Young\'s modulus value of the liver and the degree of liver fibrosis (correlation coefficient 0.16).
Supersonic SWE can generally accurately evaluate the degree of liver fibrosis in children with liver disease. However, When the liver is significantly enlarged, SWE can only evaluate liver stiffness based on Young\'s modulus values, and the degree of liver fibrosis must still be determined by pathologic biopsy.

Liver magnetic resonance elastography (MRE) is a noninvasive stiffness measurement technique that captures the tissue displacement in the phase of the signal. To limit the scanning time to a single breath-hold, liver MRE usually involves advanced readout techniques such as simultaneous multislice (SMS) or multishot methods. Furthermore, all these readout techniques require additional in-plane acceleration using either parallel imaging capabilities, such as sensitivity encoding (SENSE), or k -space undersampling, such as compressed sensing (CS). However, these methods apply a single regularization function on the complex image. This study aims to design and evaluate methods that use separate regularization on the magnitude and phase of MRE to exploit their distinct spatiotemporal characteristics. Specifically, we introduce two compressed sensing methods. The first method, termed phase-regularized compressed sensing (PRCS), applies a two-dimensional total variation (TV) prior to the magnitude and two-dimensional wavelet regularization to the phase. The second method, termed displacement-regularized compressed sensing (DRCS), exploits the spatiotemporal redundancy using 3D total variation on the magnitude. Additionally, DRCS includes a displacement fitting function to apply wavelet regularization to the displacement phasor. Both DRCS and PRCS were evaluated with different levels of compression factors in three datasets: an in silico abdomen dataset, an in vitro tissue-mimicking phantom, and an in vivo liver dataset. The reconstructed images were compared with the full sampled reconstruction, zero-filling reconstruction, wavelet-regularized compressed sensing, and a low rank plus sparse reconstruction. The metrics used for quantitative evaluation were the structural similarity index (SSIM) of magnitude (M-SSIM), displacement (D-SSIM), and shear modulus (S-SSIM), and mean shear modulus. Results from highly undersampled in silico and in vitro datasets demonstrate that the DRCS method provides higher reconstruction quality than the conventional compressed sensing method for a wide range of stiffness values. Notably, DRCS provides 24% and 22% increase in D-SSIM compared with CS for the in silico and in vitro datasets, respectively. Comparison with liver stiffness measured from full sampled data and highly undersampled data (CR=4) demonstrates that the DRCS method provided the strongest correlation ( R 2 =0.95), second-lowest mean bias (-0.18 kPa, lowest for CS with -0.16 kPa), and lowest coefficient of variation (CV=3.6%). Our results demonstrate the potential of using DRCS to improve the reconstruction quality of accelerated MRE.