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ABSTRACT Background: There is limited evidence focusing on the use of non-invasive markers to assess liver fibrosis in pediatric chronic liver diseases. Objective: The aim of the study was to evaluate the correlation between liver stiffness measurement (LSM) using transient liver elastography (TLE) and serum non-invasive markers in pediatric autoimmune hepatitis (AIH). Methods: Cross-sectional study between May 2016 and February 2020. Twenty-eight children with AIH (age range between 3 and 20 years old) who had undergone TLE and had routine serum tests were enrolled. Patients were divided into 2 groups: (1) Liver fibrosis degree ≥F2 (TLE ≥6.45 kPa) and (2)

Abstract Objectives 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. Conclusion 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. Critical relevance statement A standardized measurement protocol for WHO-recommended liver TE was first established to improve the success and efficiency of the examination procedure. Key Points 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. Graphical Abstract

Background: Cirrhosis is one of the major causes of morbidity and mortality worldwide and the second leading cause of digestive disease mortality. Portal hypertension is the main driver of cirrhosis-related complications such as ascites and variceal bleeding. Portal hypertension is defined as a hepatic venous pressure gradient >5 mm Hg, although it is clinically significant and associated with clinical complications when >10 mm Hg. Summary: Therefore, detection of clinically significant portal hypertension (CSPH) in chronic advanced liver disease or compensated cirrhosis is of paramount importance to guide the management of these patients. Key Messages: This study aimed at revising the non-invasive and invasive tools for assessment of portal hypertension and risk stratification for CSPH in patients with chronic liver disease.

BACKGROUND: The diagnosis of liver fibrosis is an important task in the management of patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The currently used diagnostic methods have a number of disadvantages such as invasiveness and high cost, or insufficient sensitivity and specificity. Therefore, the search for new non-invasive markers of liver fibrosis remains an actual challenge.AIM: To assess a diagnostic value of serum growth differentiation factor-15 (GDF-15), microfibril-associated glycoprotein 4 (MFAP-4), collagen type IV alpha1 (COL4alpha1), Mac-2 binding protein (M2BPGI) and chitinase-3-like protein 1 (YKL-40) as markers of liver fibrosis in patients with type 2 diabetes and NAFLD.MATERIALS AND METHODS: A single center cross-sectional observational study was performed. The study included 74 patients, 23 men and 51 women, aged 18 to 74 years. Liver elastography was used as reference method for the fibrosis evaluation. APRI and fib-4, non-invasive fibrosis indices, were assessed. Serum concentrations of GDF-15, MFAP-4, COL4alpha1, M2BPGI, and YKL-40 were determined by ELISA. ROC analysis was used to evaluate the sensitivity and specificity of serum markers for the diagnosis of the liver fibrosis.RESULTS: Liver fibrosis stage 1 was verified in 16 subjects, stage 2 in 12, stage 3 in 7, and stage 4 in 19. Patients with advanced liver fibrosis (stages 3–4), compared with those without severe fibrosis (stages 0–2), had higher levels of GDF-15 (p=0.003), COL4alpha1 (p=0.007), and YKL-40 (p=0.04). Patients with stage 1-2 liver fibrosis had higher levels of COL4alpha compared to those without any signs of fibrosis (p=0.02). There were no significant differences in the level of MFAP-4 and M2BPGI between patients with different severity of fibrosis. According to the ROC analysis, GDF-15, COL4alpha1 and YKL-40 have diagnostic value in the detection of severe liver fibrosis comparable to that of the APRI and fib-4 indices.CONCLUSION: GDF-15, COL4alpha1 and YKL-40 could be considered as promising non-invasive markers of liver fibrosis in patients with type 2 diabetes and NAFLD.

Objectives: 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. Conclusion: 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. Critical relevance statement: A standardized measurement protocol for WHO-recommended liver TE was first established to improve the success and efficiency of the examination procedure. Key Points: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction associated steatotic liver disease (MASLD), previously termed Non-Alcoholic Fatty Liver Disease (NAFLD), and Metabolic Syndrome (MetS) pose global health challenges rooted in metabolic dysregulation and lifestyle factors. Emerging evidence links physical inactivity with MASLD onset, commonly observed among MASLD patients. With no specific pharmacological treatment, dietary interventions and exercise are cornerstones of MASLD management. Engaging in regular physical activity has shown to improve MetS components. This observational prospective study, involving 200 patients, examines the physical activity levels of adults aged 18-74 diagnosed with MASLD or MetS using a validated questionnaire. Non-invasive assessment using transient elastography (Fibroscan) and serological scores reveal higher liver steatosis and fibrosis scores in MetS patients. A linear correlation emerged between MetS component count and physical activity index. Engaging in physical activity in adults has positive effects on various health outcomes, highlighting the need to address both metabolic and lifestyle factors for optimal health. [ABSTRACT FROM AUTHOR]

Increase in portal venous pressure (termed portal hypertension) is seen in a variety of liver diseases. Imaging tests are useful to detect portal hypertension and identify its cause. Noninvasive tests like abdominal ultrasound and Doppler studies are routinely done in clinical practice for this indication. Cross-sectional studies like computed tomography and magnetic resonance imaging are especially useful to delineate morphological abnormalities in the liver. Invasive tests like assessment of hepatic venous pressure gradient are done less frequently for specific indications. Distinctive imaging findings help differentiate the different causes of portal hypertension like cirrhosis and vascular liver disorders like noncirrhotic portal hypertension, extrahepatic portal venous obstruction, and Budd–Chiari syndrome. Radiological interventions are increasingly used to treat complications of portal hypertension like refractory ascites or refractory bleeding from gastroesophageal varices.

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 (R2=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. [ABSTRACT FROM AUTHOR]

Metabolic syndrome, liver steatosis, and subclinical atherosclerosis are interconnected conditions associated with cardiovascular disease (CVD). This study investigated the relationship between liver fibrosis (assessed via Fibroscan and serological scores) with arterial stiffness (measured by Arteriograph), carotid intima media thickness (CIMT) using ultrasound, and cardiometabolic risk factors in a cohort of 41 patients. The study evaluated the correlation between risk classifications obtained through the Systematic COronary Risk Evaluation 2 (SCORE2) diagram and these noninvasive parameters. Results demonstrated that patients with metabolic syndrome exhibited higher levels of arterial stiffness, CIMT, and liver stiffness. Moreover, these parameters correlated with elevated cardiovascular risk category determined by SCORE2. Traditional risk calculators often have limitations in assessing risk, making the integration of Fibroscan and Arteriograph valuable for refining cardiovascular risk assessment, particularly in individuals with metabolic syndrome where subclinical multiorgan damage is likely. This comprehensive approach aids in personalized risk stratification for improved clinical management. [ABSTRACT FROM AUTHOR]

Increase in portal venous pressure (termed portal hypertension) is seen in a variety of liver diseases. Imaging tests are useful to detect portal hypertension and identify its cause. Noninvasive tests like abdominal ultrasound and Doppler studies are routinely done in clinical practice for this indication. Cross-sectional studies like computed tomography and magnetic resonance imaging are especially useful to delineate morphological abnormalities in the liver. Invasive tests like assessment of hepatic venous pressure gradient are done less frequently for specific indications. Distinctive imaging findings help differentiate the different causes of portal hypertension like cirrhosis and vascular liver disorders like noncirrhotic portal hypertension, extrahepatic portal venous obstruction, and Budd–Chiari syndrome. Radiological interventions are increasingly used to treat complications of portal hypertension like refractory ascites or refractory bleeding from gastroesophageal varices. [ABSTRACT FROM AUTHOR]

Introduction and objectives: 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. Materials and methods: 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. RESULTS: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objectives: To explore the clinical application of shear wave elastography (SWE) in evaluating the degree of liver fibrosis in children. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

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.

Ruxandra Mare,1,2 Ioan Sporea,1,2 Mirela Tomescu,3 Gheorghe Nicușor Pop,3 Andrei Vitel,3 Alina Popescu,1,2 Silviu Nistorescu,1 Roxana Sirli1,2 1Department of Internal Medicine II, Gastroenterology and Hepatology Unit, Advanced Research Center in Gastroenterology and Hepatology “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 2Regional Center of Research in Advanced Hepatology, Academy of Medical Science, Timisoara, Romania; 3Department VI of Cardiology, “Victor Babeș” University of Medicine and Pharmacy, Timisoara, RomaniaCorrespondence: Roxana Sirli, Department of Internal Medicine II, Gastroenterology and Hepatology Unit, Advanced Research Center in Gastroenterology and Hepatology “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania, Tel +40723537039, Fax +40723537039, Email roxanasirli@gmail.comIntroduction: Many of the patients presenting with metabolic syndrome (MetS) also have liver steatosis (NAFLD) and some of them could develop liver fibrosis.Purpose: To develop a simple score that could rule out fibrosis, especially significant fibrosis (F≥ 2) and could be used in daily practice in patients with MetS, in order to identify patients at risk.Patients and Methods: A total of 204 patients with MetS were prospectively enrolled. Evaluation of liver fibrosis was made using Vibration Controlled Transient Elastography while evaluation of steatosis was achieved using ultrasound (US).Results: Out of 204 patients with MetS, 179 patients (87.7%) had reliable liver stiffness measurements and 22.9% (41/179) had F ≥ 2. To formulate the fibrosis predicting score, all clinical variables associated with F ≥ 2 in the univariate analysis were considered in a multivariate regression model. According to the power of correlation, by consensus, we attributed 1 point for BMI > 31.4 kg/m2, 1 point for female gender, 1 point for HDLc < 47mg/dL, 1 point for mild steatosis at US, 1.5 point for moderate and 2 points for severe steatosis.Conclusion: At an optimal cut-off value of < 3.5, our score could be used to rule-out the risk for developing at least significant fibrosis with a high negative predictive value (NPV 89.2%) in patients with MetS.Keywords: metabolic syndrome, liver steatosis, liver fibrosis, liver elastography

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. [ABSTRACT FROM AUTHOR]

Background and Aims: ElastPQ is a point shear wave elastography technique used to non‐invasively assess liver fibrosis. We compared liver stiffness measurements (LSM) by ElastPQ and fibroscan transient elastography (F‐TE) in a cohort of patients with non‐alcoholic fatty liver disease (NAFLD). We further evaluated the performance of ElastPQ in a subgroup of patients with available liver histology. Materials and Methods: We included patients with NAFLD who presented in a dedicated multidisciplinary clinic. Anthropometric parameters, blood tests and elastography measurements were obtained using F‐TE and ElastPQ as part of routine clinical care. Results: We enrolled 671 patients with NAFLD, mean age 55.8 ± 13 years, body mass index (BMI) 31.5 ± 5.7 kg/m2, 56.6% males, 41% diabetes, 53.7% hypertension, 68% dyslipidaemia. ElastPQ showed an excellent correlation with F‐TE (Spearman's r = 0.80, p <.001), which was better for mild/moderate stages of fibrosis. Independent predictors of a >2 kPa discrepancy between the two techniques were a larger waist circumference and F‐TE ≥10 kPa. In the subgroup of 159 patients with available histology, ElastPQ showed similar diagnostic accuracy with F‐TE in staging liver fibrosis (ElastPQ area under the curves 0.84, 0.83, 0.86 and 0.95, for F ≥ 1, F ≥ 2, F ≥ 3 and F = 4 respectively). Optimal cut‐off values of ElastPQ for individual fibrosis stages were lower than those of F‐TE. Conclusions: ElastPQ shows an excellent correlation with F‐TE in patients with NAFLD, which was better for lower LSM. The optimal cut‐off values of ElastPQ are lower than those of F‐TE for individual stages of fibrosis. ElastPQ has similar diagnostic accuracy to F‐TE for all stages of fibrosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: Identifying significant fibrosis is crucial to evaluate the prognosis and therapeutic interventions in patients with nonalcoholic fatty liver disease (NAFLD). We assessed the performance of acoustic radiation force impulse (ARFI) elastography, APRI, FIB-4, Forns, NFS and BARD scores in determining liver fibrosis in severe obesity. Subjects and methods: A prospective study included 108 patients undergoing bariatric surgery. Liver biopsy specimens were obtained intraoperatively and classified according to the NAFLD Activity Score. Patients were assessed with serological markers and shear wave velocity of the liver was measured with the Siemens S2000 ultrasound system preoperatively. Optimal cut-off values were determined using the area under the receiver operating characteristic curves (AUROC). Results: In the entire cohort prevalence of NAFLD was 80.6%, steatohepatitis 25.9% and significant fibrosis 19.4%. The best tests for predicting significant fibrosis were FIB-4 and Forns scores (both AUROC 0.78), followed by APRI (AUROC 0.74), NFS (AUROC 0.68), BARD (AUROC 0.64) and ARFI (AUROC 0.62). ARFI elastography was successful in 73% of the patients. Higher body mass index (BMI) correlated with invalid ARFI measurements. In patients with BMI < 42 kg/m2, ARFI showed 92.3% sensitivity and 82,6% specificity for the presence of significant fibrosis, with AUROC 0.86 and cut-off 1.32 m/s. Conclusions: FIB-4 and Forns scores were the most accurate for the prediction of significant fibrosis in bariatric patients. Applicability and accuracy of ARFI was limited in individuals with severe obesity. In patients with BMI < 42 kg/m2, ARFI elastography was capable for predicting significant fibrosis with relevant accuracy.

Timely discriminating biliary atresia (BA) from other causes of cholestasis is important but challenging. To develop a useful diagnostic nomogram and a simplified scoring system to diagnosing BA. All medical records of the patients who were consecutively admitted to our institution with cholestasis from March 2016 to December 2020 were retrospectively searched. The patients were allocated to the derivation cohort (n = 343) and the validation cohort (n = 246). Multivariable logistic regression models were used to construct the nomogram. The nomogram was validated in both cohorts. The simplified risk score was derived from the nomogram. The nomogram was constructed based on presence of clay stool, gallbladder length, gallbladder emptying index, shear wave elastography value, and gamma-glutamyl transferase level. This model showed good calibration and discrimination ability, with the C-index of 0.968 (95% CI: 0.951–0.984). The discriminating ability is most prominent in the 61–90 days group, with AUC of 0.982 (95% CI: 0.955–1.000). The simplified risk score identified most patients with very high or low risk of BA, and was capable of exempting 64.3% non-BA patients from intraoperative cholangiogram procedure. This novel diagnostic nomogram had good discrimination and calibration abilities. The simplified scoring system showed significant clinical utility. [ABSTRACT FROM AUTHOR]

Purpose: People with obesity often develop non-alcoholic fatty liver disease (NAFLD) and are at high risk of progression to non-alcoholic steatohepatitis (NASH). Few therapies are effective other than bariatric surgery. We therefore analyzed data from duodenal-jejunal bypass liner (DJBL) patients regarding steatosis, fibrosis, and NASH. Methods: Consecutive DJBL patients with type 2 diabetes underwent standardized assessments up to device removal at 48 weeks. These included aspartate and alanine transaminase (AST, ALT), controlled attenuation parameter (CAP, for steatosis), and liver stiffness measurement (LSM, for fibrosis). The NAFLD fibrosis score (NFS), fibrosis-4 score (FIB4), and enhanced liver fibrosis (ELF) test were also used to assess fibrosis and the Fibroscan-AST (FAST) score to assess NASH. Mixed models were used and missing data were accounted for with multiple imputation. Results: Thirty-two patients (18 female, mean age 55.1, mean BMI 40.2 kg/m2) were included. After 48 weeks, the change compared to baseline with 95% CI was a factor 0.74 (0.65 to 0.84) for AST, 0.63 (0.53 to 0.75) for ALT, and a difference of − 0.21 (− 0.28 to − 0.13) for FAST, all with p < 0.001. Fibrosis based on LSM, NFS, and ELF did not change whereas FIB4 exhibited slight improvement. Eight DJBL were explanted early due to device-related complications and eight complications led to hospitalization. Conclusions: One year of DJBL therapy is associated with relevant improvements in non-invasive markers of steatosis and NASH, but not fibrosis, and is accompanied by a substantial number of complications. Given the lack of alternatives, DJBL deserves further attention. [ABSTRACT FROM AUTHOR]

Background and aims: Chronic hepatitis B virus (CHB) infection remains a major global health burden and the non-invasive and accurate diagnosis of significant liver fibrosis (≥ F2) in CHB patients is clinically very important. This study aimed to assess the potential of the joint use of ultrasound images of liver parenchyma, liver stiffness values, and patients' clinical parameters in a deep learning model to improve the diagnosis of ≥ F2 in CHB patients. Methods: Of 527 CHB patients who underwent US examination, liver elastography and biopsy, 284 eligible patients were included. We developed a deep learning-based data integration network (DI-Net) to fuse the information of ultrasound images of liver parenchyma, liver stiffness values and patients' clinical parameters for diagnosing ≥ F2 in CHB patients. The performance of DI-Net was cross-validated in a main cohort (n = 155) of the included patients and externally validated in an independent cohort (n = 129), with comparisons against single-source data-based models and other non-invasive methods in terms of the area under the receiver-operating-characteristic curve (AUC). Results: DI-Net achieved an AUC of 0.943 (95% confidence interval [CI] 0.893–0.973) in the cross-validation, and an AUC of 0.901 (95% CI 0.834–0.945) in the external validation, which were significantly greater than those of the comparative methods (AUC ranges: 0.774–0.877 and 0.741–0.848 for cross- and external validations, respectively, ps < 0.01). Conclusion: The joint use of ultrasound images of liver parenchyma, liver stiffness values, and patients' clinical parameters in a deep learning model could significantly improve the diagnosis of ≥ F2 in CHB patients. [ABSTRACT FROM AUTHOR]

Tudor Parvanescu,1 Andrei Vitel,1 Ioan Sporea,2 Ruxandra Mare,2 Bogdan Buz,1 Diana Aurora Bordejevic,1 Mirela Cleopatra Tomescu,1 Sergiu Florin Arnautu,3 Vlad Ioan Morariu,1 Ioana Mihaela Citu1 1Cardiology Department, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania; 2Department of Gastroenterology and Hepatology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania; 3Department of Neurology, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaCorrespondence: Diana Aurora BordejevicCardiology Department, Victor Babe” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, Timisoara, RomaniaTel +40 734600550Fax +40 256220636Email aurora.bordejevic@umft.roBogdan BuzCardiology Department, “Victor Babes” University of Medicine and Pharmacy, 2nd Eftimie Murgu Square, Timisoara, RomaniaTel +40 756346910Email buzbogdan93@gmail.comPurpose: The constitutive elements of the metabolic syndrome (MetS) are linked with both non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. Controlled attenuation parameter (CAP), and vibration controlled transient elastography (VCTE), are able to detect and quantify NAFLD, while conventional and two-dimensional speckle tracking echocardiography (2D-STE) is capable to identify subclinical changes in cardiac function. We wanted to evaluate whether there is any correspondence between left ventricular (LV) diastolic dysfunction and different degrees of liver steatosis and fibrosis in MetS subjects with NAFLD.Patients and Methods: A total of 150 adult subjects having MetS and a normal left ventricular (LV) systolic function were recorded in the study, while 150 age- and sex- matched adults without MetS were enrolled as controls. NAFLD was established by VCTE and CAP. The left heart systolic and diastolic function was evaluated by conventional and 2D-ST echocardiography. Left atrial (LA) stiffness was calculated as the ratio between the E/A ratio and the LA reservoir-strain.Results: In univariate regression analysis, the variables associated with LV diastolic dysfunction in MetS patients were: liver steatosis grade ≥ 2, liver fibrosis grade ≥ 2, the longitudinal LA peak strain during the reservoir phase, the LA strain rate during ventricular contraction and the LA stiffness. In multivariate logistic regression, two variables were selected as independent predictors of LV diastolic dysfunction, namely the liver stiffness (P=0.0003) and the LA stiffness (P< 0.0001). LA stiffness predicted subclinical LV diastolic dysfunction in MetS patients with a sensitivity of 45% and a specificity of 96% when using a cut-off value > 0.38, and was significantly correlated with liver steatosis stage ≥ 2 and liver fibrosis stage ≥ 2.Conclusion: The present study confirms the association between liver stiffness, LA stiffness and LV diastolic dysfunction in MetS patients. Our study suggests that liver elastography and 2D-STE should become habitual assessments in MetS patients.Keywords: metabolic syndrome, strain and strain‑rate imaging, left atrial stiffness, left ventricular diastolic dysfunction, liver elastography, liver steatosis and fibrosis

Introduction and objectives: 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. Materials and methods: 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. RESULTS: 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. Conclusions: 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.

Chronic liver disease (CLD) is common in clinical practice, and the estimation of liver fibrosis (FIB) is crucial for the treatment of these patients. Liver elastography is more widely used in the evaluation of hepatic steatosis and FIB. Acoustic radiation force impulse (ARFIs) are an imaging technique which is available on ultrasonography machines to indicate tissue stiffness of various organs as it correlates with tissue elasticity. Various etiologies can cause moderate-to-severe hepatic FIB which can lead to altered liver function with structural and biochemical abnormalities which eventually result in liver failure. Commercially available ultrasound machines with incorporated ability for shear-wave (SW) technology and available software systems can perform ARFI. Usually, curved array 3.5–4 MHz transducers are used for obtaining SW velocities. We aim to review the clinical applications of ARFI as a noninvasive method using SW velocity measurements to assess the severity of liver FIB in liver parenchymal diseases. In this article, we have discussed the efficacy of quantitative assessment to evaluate the severity of liver disease which has a direct impact on the management and outcome of CLD.

Andrei Vitel,1,* Ioan Sporea,2 Ruxandra Mare,2 Christian Banciu,2 Diana-Aurora Bordejevic,1,* Tudor Parvanescu,1 Ioana Mihaela Citu,1 Mirela Cleopatra Tomescu1 1Cardiology Department, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 2Gastroenterology Department, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania*These authors contributed equally to this workCorrespondence: Ioana Mihaela CituCardiology Department, “Victor Babes” University of Medicine and Pharmacy, 2 nd Eftimie Murgu Square, Timisoara, RomaniaTel +40 724353666Fax +40 256220636Email ioanamihaela2010@gmail.comPurpose: The components of metabolic syndrome (MS) are risk factors for developing both cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Strain (SI) and strain‑rate imaging (SRI) are able to recognize early changes in cardiac function. Vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP) detect and quantify liver fibrosis and steatosis. We aimed to assess whether there is any correlation between liver fibrosis and steatosis and left ventricular (LV) dysfunction in MS patients.Patients and Methods: A total of 150 adults with MS were registered in the study. They were compared with a control group of 150 age- and sex-matched adults without MS. After the classic echocardiographic assessment of LV function, two-dimensional speckle echocardiography (2D-STE) was used to evaluate LV peak systolic strain (S) and peak systolic strain rate (SR), while liver steatosis and fibrosis were evaluated by VCTE and CAP.Results: LV diastolic dysfunction was significantly more frequent among the patients with MS. We found significant differences between the two groups regarding the presence of subtle LV systolic dysfunction, detected by reduced values of S and SR. The risk for LV diastolic dysfunction was 3.6 times higher in MS with severe steatosis and 8 times higher in patients with severe fibrosis, P< 0.0001. The risk for LV systolic dysfunction was double in MS with severe steatosis and 1.7 times higher in MS with severe fibrosis, P< 0.0001.Conclusion: In MS patients with normal LV ejection fraction, conventional echocardiography parameters identified diastolic LV dysfunction, while SI and SRI identified subtle impairment of systolic LV dysfunction. The presence of hepatic steatosis and fibrosis increases significantly the risk for cardiac dysfunction in MS patients (P< 0.0001).Keywords: metabolic syndrome, left ventricular function, strain and strain‑rate imaging, liver steatosis and fibrosis, liver elastography

Introduction and objectives: Recent findings pointed out that even low-risk esophageal varices (EVs) are markers of severe prognosis. Accordingly, we analyzed spleen stiffness (SS) as a non-invasive method to predict EVs of any grade in a cohort of patients with compensated liver cirrhosis. Method: We measured SS and liver stiffness (LS) using point-Shear-Wave Elastography (pSWE) with Philips Affiniti 70 system in 210 cirrhotic patients who had undergone endoscopic screening for EVs. We compared SS and LS predictive capability for EVs of any grade. Results: SS was higher in cirrhotic patients with EVs if compared to patients without EVs (p

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.

Background Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a cause of chronic liver disease. It can lead to complications such as decompensated liver cirrhosis and hepatocellular carcinoma. Objectives This study aimed to assess liver stiffness using point shear wave elastography in patients with diabetes and NAFLD and to compare the results with the FIB-4 (fibrosis-4) score, AST/ALT (aspartate aminotransferase-to-alanine aminotransferase) ratio, and APRI (AST-to-Platelet Ratio Index). Materials and methods A cross-sectional study was conducted on type 2 diabetes patients who underwent point shear wave liver elastography for liver stiffness estimation between January 2020 and February 2023. Demographic data such as age, sex, and laboratory data (AST, ALT, and platelet count) were recorded. FIB-4 score, APRI, and AST/ALT ratio were calculated for these patients. The results of the FIB-4 score and APRI were then compared with the shear wave liver elastography fibrosis scores. Results The analysis included 60 patients, of whom 50 (83.33%) were male, with a mean age of 44.8 years (SD: 11.02; range: 21-69). Thirty-six patients (60%) had significant fibrosis. There was a significant positive correlation between the shear wave elastography results and the FIB-4 and APRI scores. Conclusion The findings revealed that nearly two-thirds of the study group had significant fibrosis (≥F2), highlighting the need for early NAFLD diagnosis and treatment. Noninvasive laboratory serum markers, in conjunction with shear wave liver elastography, are useful for diagnosing severe fibrosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Sahyadri Hospitals Private Limited Biomedical and Health Research Committee issued approval N/A. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kelkar et al.)

Introduction: Liver fibrosis is a progressive disorder that if diagnosed early and staged precisely, allows early clinical intervention that may hinder or slow down the progression to end stage decompensated cirrhosis. Grading of hepatic fibrosis is important not only for diagnosis but also for prognostic evaluation, planning appropriate therapy, and follow-up of patients with chronic viral hepatitis. Liver biopsy has been considered the reference standard for grading liver fibrosis. As liver biopsy is invasive and associated with complications, non invasive serological and imaging techniques like Shear Wave Elastography (SWE) and Aminotransferase Platelet Ratio Index (APRI) have come to the spotlight. Aim: To evaluate SWE alone and together with APRI as a reliable alternative to liver biopsy for diagnosing and grading hepatic fibrosis in chronic viral hepatitis. Materials and Methods: This case control study was conducted over a period of 18 months from October 2017 to March 2019, at a tertiary care hospital in New Delhi, India. Total 120 subjects (60 cases of chronic viral hepatitis and 60 case matched healthy volunteers as controls) were enrolled in the study. Biopsy could not be performed in 10 cases so these cases and their matched controls were excluded from the statistical analysis. SWE was performed using a 1-5 MHz curvilinear transducer (Philips iU22x MATRIX). APRI and mean of six SWE measurements (in kilopascals) were calculated for all subjects. The analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. Results: Among all 50 cases of chronic hepatitis who have undergone biopsy, the mean SWE values corresponding to the histopathological grade of fibrosis i.e., F0, F1, F2, F3 and F4 was found to be 4.48±1.05, 7.16±0.75 kPa, 8.08±1.05 kPa, 8.44±0.47 kPa and 16.01±3.78 kPa respectively. The mean APRI values of the cases in F1, F2 and F3 grades showed significant overlap (cut off value between 0.5-1.5). Also, when APRI was used along with SWE, does not have a statistically significant contribution to improve its diagnostic accuracy in liver fibrosis grading. Conclusion: Shear wave elastography has high accuracy in detecting and grading of fibrosis. APRI does not appear to have a significant role in the grading of liver fibrosis however it can be combined with SWE for post-treatment follow-up of chronic viral hepatitis patients thus avoiding the need for repeated biopsy. [ABSTRACT FROM AUTHOR]

Introduction: Liver fibrosis is a progressive disorder that if diagnosed early and staged precisely, allows early clinical intervention that may hinder or slow down the progression to end stage decompensated cirrhosis. Grading of hepatic fibrosis is important not only for diagnosis but also for prognostic evaluation, planning appropriate therapy, and follow-up of patients with chronic viral hepatitis. Liver biopsy has been considered the reference standard for grading liver fibrosis. As liver biopsy is invasive and associated with complications, non invasive serological and imaging techniques like Shear Wave Elastography (SWE) and Aminotransferase Platelet Ratio Index (APRI) have come to the spotlight. Aim: To evaluate SWE alone and together with APRI as a reliable alternative to liver biopsy for diagnosing and grading hepatic fibrosis in chronic viral hepatitis. Materials and Methods: This case control study was conducted over a period of 18 months from October 2017 to March 2019, at a tertiary care hospital in New Delhi, India. Total 120 subjects (60 cases of chronic viral hepatitis and 60 case matched healthy volunteers as controls) were enrolled in the study. Biopsy could not be performed in 10 cases so these cases and their matched controls were excluded from the statistical analysis. SWE was performed using a 1-5 MHz curvilinear transducer (Philips iU22x MATRIX). The APRI and the mean of six SWE measurements (in kilopascals) were calculated for all subjects. The analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. Results: Among all 50 cases of chronic hepatitis who have underwent biopsy, the mean SWE values corresponding to the histopathological grade of fibrosis i.e., F0, F1, F2, F3 and F4 was found to be 4.48±1.05 kPa, 7.16±0.75 kPa, 8.08±1.05 kPa, 8.44±0.47 kPa and 16.01±3.78 kPa, respectively. The mean APRI values of the cases in F1, F2 and F3 grades showed significant overlap (cut off value between 0.5-1.5). Also, when APRI was used along with SWE, does not have a statistically significant contribution to improve its diagnostic accuracy in liver fibrosis grading. Conclusion: Shear wave elastography has high accuracy in detecting and grading of fibrosis. APRI does not appear to have a significant role in the grading of liver fibrosis however it can be combined with SWE for post-treatment follow-up of chronic viral hepatitis patients thus avoiding the need for repeated biopsy.

Background: Advanced liver fibrosis and cirrhosis represent independent risk factors for hepatocellular carcinoma (HCC). There is also evidence suggesting that several etiologies of chronic liver disease elevate the risk for non-hepatic cancers, including nonalcoholic fatty liver disease (NAFLD), alcohol abuse, and hepatitis C infection. In the present study, we aim to characterize the cancer incidence in patients with chronic liver disease and assess the prognostic value of non-hepatic cancer on the decompensation events of this population. Methods: We retrospectively reviewed the electronic medical records of patients who underwent transient elastography (TE) of liver, at John H. Stroger Hospital in Cook County, Chicago, IL. We identified patients who had decompensation of cirrhosis. We also extracted their cancer history. The cancer profiles of the cohort were compared by the presence or absence of advanced liver fibrosis. We then performed univariate and multivariate forward stepwise Cox regression analysis to identify the significant risk factors for the decompensation events and plotted Kaplan-Meier curve to demonstrate the significance of cancer in the prediction of decompensation events. Results: We identified a total of 3097 patients who underwent TE. A total of 45 liver decompensation events were documented. In the univariate Cox regression model, MELD-Na score (hazard ratio (HR) 1.25, p < 0.001), liver stiffness measurement (HR 1.05, p = 0.004), and history of any cancer (HR 3.81, p = 0.001) emerged as predictors of decompensation. Non-hepatic cancer proved to be a significant predictor of decompensation (HR 3.57, p = 0.002). Conclusion: The present study represents the first attempt to the best of our knowledge to describe the cancer incidence in this high-risk population. We found that non-HCC cancers independently predict hepatic decompensation events, which is an intriguing finding. We propose that physicians should be more vigilant to cancer history of patients with chronic liver disease as it might provide valuable prognostic information and guide individualized treatment and surveillance plans. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease is the most common cause of liver-related morbidity and mortality in the world. However, no effective pharmacological treatment for this condition has been found.Purpose: This study evaluated the effect of a nutraceutical containing bioactive components from Bergamot citrus and wild cardoon as a treatment for individuals with fatty liver disease. The primary outcome measure was the change in liver fat content.Methods: A total of 102 patients with liver steatosis were enrolled in a double-blind placebo controlled clinical trial. The intervention group received a nutraceutical containing a Bergamot polyphenol fraction and Cynara Cardunculus extract, 300 mg/day for 12 weeks. The control group received a placebo daily. Liver fat content, by transient elastography, serum transaminases, lipids and glucose were measured at the baseline and the end of the study.Results: We found a greater liver fat content reduction in the participants taking the nutraceutical rather than placebo (−48.2 ± 39 vs. −26.9 ± 43 dB/m, p = 0.02); The percentage CAP score reduction was statistically significant in those with android obesity, overweight/obesity as well as in women. However, after adjustment for weight change, the percentage CAP score reduction was statistically significant only in those over 50 years (44 vs. 78% in placebo and nutraceutical, respectively, p = 0.007).Conclusions: This specific nutraceutical containing bioactive components from Bergamot and wild cardoon reduced the liver fat content during 12 weeks in individuals with liver steatosis over 50 years. If confirmed, this nutraceutical could become the cornerstone treatment of patients affected by liver steatosis.Clinical Trial Registration:www.isrctn.com, identifier ISRCTN12833814.

Chronic liver disease affects 185 million population worldwide. It encompasses a heterogenous disease spectrum, but all can lead to the development of liver fibrosis. The degree of liver fibrosis is not only a prognosticator, but has also been used to guide the treatment strategy and to evaluate treatment response. Traditionally, staging of liver fibrosis is determined on histological analysis using samples obtained from an invasive liver biopsy. Ultrasound-based liver elastography is a non-invasive method of assessing diffuse liver disease in patients with known chronic liver disease. The use of liver elastography has led to a significant reduction in the number of liver biopsies performed to assess the severity of liver fibrosis and a liver biopsy is now reserved for only select sub-groups of patients. The aim of this review article is to discuss the key findings and current evidence for ultrasound-based elastography in diffuse liver disease as well as the technical challenges and to evaluate the potential research direction. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease is the most common cause of liver-related morbidity and mortality in the world. However, no effective pharmacological treatment for this condition has been found. Purpose: This study evaluated the effect of a nutraceutical containing bioactive components from Bergamot citrus and wild cardoon as a treatment for individuals with fatty liver disease. The primary outcome measure was the change in liver fat content. Methods: A total of 102 patients with liver steatosis were enrolled in a double-blind placebo controlled clinical trial. The intervention group received a nutraceutical containing a Bergamot polyphenol fraction and Cynara Cardunculus extract, 300 mg/day for 12 weeks. The control group received a placebo daily. Liver fat content, by transient elastography, serum transaminases, lipids and glucose were measured at the baseline and the end of the study. Results: We found a greater liver fat content reduction in the participants taking the nutraceutical rather than placebo (−48.2 ± 39 vs. −26.9 ± 43 dB/m, p = 0.02); The percentage CAP score reduction was statistically significant in those with android obesity, overweight/obesity as well as in women. However, after adjustment for weight change, the percentage CAP score reduction was statistically significant only in those over 50 years (44 vs. 78% in placebo and nutraceutical, respectively, p = 0.007). Conclusions: This specific nutraceutical containing bioactive components from Bergamot and wild cardoon reduced the liver fat content during 12 weeks in individuals with liver steatosis over 50 years. If confirmed, this nutraceutical could become the cornerstone treatment of patients affected by liver steatosis. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN12833814. [ABSTRACT FROM AUTHOR]

More than 100 attendees from Australia, Austria, Belgium, Canada, China, Germany, Hong Kong, Indonesia, Japan, Malaysia, the Netherlands, the Philippines, Republic of Korea, Singapore, Sweden, Switzerland, the United Kingdom, and the United States convened in Singapore for the 2019 ISMRM‐sponsored workshop on MRI of Obesity and Metabolic Disorders. The scientific program brought together a multidisciplinary group of researchers, trainees, and clinicians and included sessions in diabetes and insulin resistance; an update on recent advances in water–fat MRI acquisition and reconstruction methods; with applications in skeletal muscle, bone marrow, and adipose tissue quantification; a summary of recent findings in brown adipose tissue; new developments in imaging fat in the fetus, placenta, and neonates; the utility of liver elastography in obesity studies; and the emerging role of radiomics in population‐based "big data" studies. The workshop featured keynote presentations on nutrition, epidemiology, genetics, and exercise physiology. Forty‐four proffered scientific abstracts were also presented, covering the topics of brown adipose tissue, quantitative liver analysis from multiparametric data, disease prevalence and population health, technical and methodological developments in data acquisition and reconstruction, newfound applications of machine learning and neural networks, standardization of proton density fat fraction measurements, and X‐nuclei applications. The purpose of this article is to summarize the scientific highlights from the workshop and identify future directions of work. [ABSTRACT FROM AUTHOR]

Intruduction and objectives: Recent findings pointed out that even low-risk esophageal varices (EVs) are markers of severe prognosis. Accordingly, we analyzed spleen stiffness (SS) as a non-invasive method to predict EVs of any grade in a cohort of patients with compensated liver cirrhosis. Method: We measured SS and liver stiffness (LS) using point-Shear-Wave Elastography (pSWE) with Philips Affiniti 70 system in 210 cirrhotic patients who had undergone endoscopic screening for EVs. We compared SS and LS predictive capability for EVs of any grade. Results: SS was higher in cirrhotic patients with EVs if compared to patients without EVs (p < 0.001). The cut-off analysis detected 31 kPa (100% sensitivity and negative predictive value) as the value to rule-out EVs and 69 kPa (100% specificity and positive predictive value) to rule-in EVs. Besides, we developed the Spleen Stiffness Probability Index (SSPI), that can provide a probability of presence/absence of EVs. SSPI was the best model according to all discriminative and calibration metrics (AIC = 120, BIC = 127, AUROC = 0.95, Pseudo-R2 = 0.74). SS demonstrated higher correlation with spleen bipolar diameter and spleen surface (r = 0.52/0.55) if compared to LS (r = 0.30/0.25) - and with platelet count as well (r = 0.67 vs r = 0.4). Conclusion: SS showed significantly higher performance than other parameters, proving to be the best non-invasive test in the screening of EVs: by directly applying SS cut-off of 31 kPa, our department could have safely avoided endoscopy in 36% of patients. Despite cut-off analyses, it was possible to create a probability model that could further stratify low-risk from high-risk patients (for any grade of EVs). [ABSTRACT FROM AUTHOR]

Purpose of Review: Chronic hepatitis C (CHC) infection remains a significant global public health burden and is associated with significant morbidity and mortality due to complications of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). All oral direct-acting antivirals (DAAs) are associated with high rates of sustained virologic response (SVR). Pre-treatment assessment for liver fibrosis remains of high importance as it may impact treatment choice, treatment duration, and signal the presence of cirrhosis for which variceal screening and HCC surveillance are warranted. Recent Findings: Non-invasive fibrosis assessment tools have largely replaced gold standard liver biopsy in routine clinical practice. Herein, we review key modalities of noninvasive testing with serum and imaging biomarkers, summarize current guideline recommendations, and propose an algorithm for real-world application in clinical practice. Summary: Careful history and exam, laboratory assessment, liver imaging, and a two-test noninvasive fibrosis strategy can reliably identify cirrhosis in patients with CHC infection. [ABSTRACT FROM AUTHOR]

Untreated hepatic iron overload causes hepatic fibrosis and cirrhosis and can predispose to hepatocellular carcinoma. MR elastography (MRE) provides a non-invasive means to measure liver stiffness, which correlates with liver fibrosis but standard gradient recalled echo (GRE)-based MRE techniques fail in patients with high iron due to very low hepatic signal. Short echo time (TE) 2D spin echo echoplanar imaging (SE-EPI)-based MRE may allow measurement of stiffness in the iron loaded liver. The purpose of this study was to describe the use of such an MRE sequence in patients undergoing liver iron quantification by MRI. In our preliminary study of 43 patients with mean LIC of 9.3 mg/g (range 1.8-21.5 mg/g), liver stiffness measurements could be made in 77% (33/43) of patients with a short TE, SE-EPI based MRE sequence. On average, mean LIC in patients with failed MRE was higher than in those with successful MRE (15.9 mg/g dry weight vs. 7.3 mg/g), but a cut-off value for successful MRE could not be established. Seven patients (21% of those with successful MRE) had liver stiffness values suggestive of the presence of significant fibrosis (> 2.49 kPa). A short TE, SE-EPI based MR elastography sequence allows successful measurement of liver stiffness in a majority of patients with liver iron loading, potentially allowing non-invasive screening for fibrosis. [ABSTRACT FROM AUTHOR]

We performed an epidemiologic study to assess the prevalence of chronic viral hepatitis in inflammatory bowel disease (IBD) and to detect their possible relationships. Methods: It was a single centre cohort cross-sectional study, during October 2016 and October 2017. Consecutive IBD adult patients and a control group of non-IBD subjects were recruited. All patients underwent laboratory investigations to detect chronic hepatitis B (HBV) and C (HCV) infection. Parameters of liver function, elastography and IBD features were collected. Univariate analysis was performed by Student’s t or chi-square test. Multivariate analysis was performed by binomial logistic regression and odds ratios (ORs) were calculated. We enrolled 807 IBD patients and 189 controls. Thirty-five (4.3%) had chronic viral hepatitis: 28 HCV (3.4%, versus 5.3% in controls, p = 0.24) and 7 HBV (0.9% versus 0.5% in controls, p = 0.64). More men were observed in the IBD–hepatitis group (71.2% versus 58.2%, p < 0.001). Patients with IBD and chronic viral hepatitis had a higher mean age and showed a higher frequency of diabetes, hypertension and wider waist circumference. They suffered more frequently from ulcerative colitis. Liver stiffness was greater in subjects with IBD and chronic viral hepatitis (7.0 ± 4.4 versus 5.0 ± 1.2 KPa; p < 0.001). At multivariate analysis, only old age directly correlated with viral hepatitis risk (OR = 1.05, 95%CI 1.02–1.08, p < 0.001). In conclusion, the prevalence of HBV/HCV in IBD is low in our region. Age may be the only independent factor of viral hepatitis–IBD association. Finally, this study firstly measured liver stiffness in a large scale, showing higher values in subjects with both diseases.

Background: Obesity is a primary limiting factor in liver stiffness measurement (LSM). The impact of obesity has always been evaluated in terms of body mass index (BMI), without studying the effects of skin-to-liver distance (SLD) on LSM. We studied the impact of SLD on LSM in a cohort of obese patients undergoing bariatric surgery and intra-operatory liver biopsy. Materials and Methods: 299 patients underwent LSM by point-shear wave elastography (ElastPQ protocol), with two different ultrasound machines. SLD was measured as the distance between the skin and the liver capsule, perpendicular to where the region of interest (ROI) was positioned. We used the following arbitrary cut-offs:

Background: Liver stiffness measurement (LSM) is crucial for appropriate fibrosis staging in patients with ongoing hepatitis C virus (HCV) infection. However, there is still an ongoing debate on the impact of serum transaminases (aspartate-aminotransferase, AST; alanine-aminotransferase, ALT) on LSM. Methods: We selected 110 patients undergoing HCV eradication therapy with LSM compatible with significant liver fibrosis. LSM was evaluated prior to therapy and one year after HCV eradication. Results: LSM showed a median decrease of 35% from baseline values, and 67 (61%) patients showed posttreatment values compatible with lower fibrosis stages. We developed two logistic regression models to determine the probability of liver fibrosis overestimation according to serum transaminase. The probability of overestimation of two or more fibrosis grade is equal to (1) 50% for AST of 99 IU/L (2.2 ULN) and ALT of 90.5 IU/L (2 ULN), (2) 80% for AST of 123.5 IU/L (2.74 ULN) and ALT of 101.5 IU/L (2.25 ULN), and (3) reaches 100% for AST of 211 IU/L (4.7 ULN) and ALT of 140 IU/L (3.1 ULN). Conclusions: This study highlights the impact of serum transaminases on LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in patients with HCV infection.

Background: Assessing the hepatic status of children with CHD is very important in the post-operative period. This study aimed to assess the usefulness of paediatric liver T1/T2 values and to evaluate the impact of respiration on liver T1/T2 values., Methods: Liver T1/T2 values were evaluated in 69 individuals who underwent cardiac MRI. The mean age of the participants was 16.2 ± 9.8 years. Two types of imaging with different breathing methods were possible in 34 participants for liver T1 values and 10 participants for liver T2 values., Results: The normal range was set at 620-830 msec for liver T1 and 25-40 ms for liver T2 based on the data obtained from 17 healthy individuals. The liver T1/T2 values were not significantly different between breath-hold and free-breath imaging (T1: 769.4 ± 102.8 ms versus 763.2 ± 93.9 ms; p = 0.148, T2: 34.9 ± 4.0 ms versus 33.6 ± 2.4 ms; p = 0.169). Higher liver T1 values were observed in patients who had undergone Fontan operation, tetralogy of Fallot operation, or those with chronic viral hepatitis. There was a trend toward correlation between liver T1 values and liver stiffness (R = 0.65, p = 0.0004); and the liver T1 values showed a positive correlation with the shear wave velocity (R = 0.62, p = 0.0006)., Conclusions: Liver T1/T2 values were not affected by breathing patterns. Because liver T1 values tend to increase with right heart overload, evaluation of liver T1 values during routine cardiac MRI may enable early detection of future complications.

The evaluation of patients with early hepatocellular carcinoma (HCC) referred for liver resection is still a matter of debate. Aims: 1) to compare liver stiffness measurement (LSM) by transient elastography with hepatic venous pressure gradient (HVPG) in the prediction of decompensation after liver resection in patients with cirrhosis and early HCC; 2) to identify which definition for posthepatectomy liver failure is better associated with survival.Material and Methods: Fifty-one patients (MELD score of 10±3) were included. In this group, 34 patients underwent HVPG measurement, of which 13 (38%) had clinically significant portal hypertension (CSPH) and 35 patients underwent LSM (21.8±17.9 kPa). The study's end-points were: posthepatectomy liver failure (PHLF) defined according to International Study Group of Liver Surgery criteria and 3-month decompensation defined as de novo ascites, variceal bleeding, jaundice, hepatic encephalopathy and acute kidney injury. The performance of LSM compared to HVPG in predicting the end-points were assessed by AUROC curves and accuracy.Results: Twenty (39%) patients developed PHLF and 15 (29%) developed decompensationat 3 months. Three-month decompensation tended to be better correlated with survival. LSM performed well in predicting decompensation at 3 months (AUROC=0.78, 95%CI: 0.63-0.94; p=0.01), comparable with HVPG (AUROC=0.89, 95%CI: 0.79-1.00; p<0.01) (DeLong test p=0.21). LSM was not sufficiently accurate to predict PHLF.Conclusion: LSM has a similar performance to HVPG in predicting decompensation at 3 months in patients with early HCC submitted to liver resection. Three-month decompensation is better associated with survival. [ABSTRACT FROM AUTHOR]

Shear wave elastography methods are able to accurately measure tissue stiffness, allowing these techniques to monitor the progression of hepatic fibrosis. While many methods rely on acoustic radiation force to generate shear waves for 2-D imaging, probe oscillation shear wave elastography (PROSE) provides an alternative approach by generating shear waves through continuous vibration of the ultrasound probe while simultaneously detecting the resulting motion. The generated shear wave field in in vivo liver is complicated, and the amplitude and quality of these shear waves can be influenced by the placement of the vibrating probe. To address these challenges, a real-time shear wave visualization tool was implemented to provide instantaneous visual feedback to optimize probe placement. Even with the real-time display, it was not possible to fully suppress residual motion with established filtering methods. To solve this problem, the shear wave signal in each frame was decoupled from motion and other sources through the use of a parameter-free empirical mode decomposition before calculating shear wave speeds. This method was evaluated in a phantom as well as in in vivo livers from five volunteers. PROSE results in the phantom as well as in vivo liver correlated well with independent measurements using the commercial General Electric Logiq E9 scanner. [ABSTRACT FROM PUBLISHER]

Background: Acoustic radiation force impulse (ARFI) elastography has been used to assess liver stiffness non-invasively. However, its usefulness in alpha-1 antitripsin-deficient (AATD) individuals is unknown. Purpose: To assess if liver fibrosis is present in a cohort of AATD individuals using ARFI elastography. Material and Methods: Eighty-three participants aged 38-39 years, except for two who were aged 40 years, underwent ultrasound elastography of the liver with ARFI technique. Twenty-nine were homozygote ZZ genotype, PiZZ (14 men, 15 women); 12 were SZ genotype, Pi SZ (8 men, 4 women), and 42 were healthy volunteers, PiMM (16 men, 26 women). Three specific liver anatomical regions were examined: segments 2/3 (left lobe) in the subcostal plane, and 5/6 and 7/8 (right lobe) in the intercostal space. In each region, three measurements were registered. Results: There was no statistically significant difference between ARFI-median in the AATD group and the control group (P value=0.877) and neither between AATD groups (PiZZ and PiSZ) with a P value=0.259. The ARFI-median was lower in the right liver lobe than in the left lobe in all groups and the difference between both lobes was statistically significant (P=0.001). No statistically significant difference was found in ARFI-median of the right liver lobe between the AATD group and the control group (P=0.759), nor between the AATD group (P=0.384). No gender difference was found in ARFI-median. Conclusions: ARFI values in AATD individuals aged 38-39 years showed no difference compare to healthy participants. [ABSTRACT FROM AUTHOR]