The Non-Invasive Ultrasound-Based Assessment of Liver Viscosity in a Healthy Cohort.

Liver fibrosis is the most significant prognostic factor in chronic liver disease (CLD). Clinical practice guidelines recommend the use of non-invasive techniques, such as two-dimensional shear-wave elastography (2D-SWE), to assess liver stiffness as a marker of fibrosis. Several other factors influence liver stiffness in addition to liver fibrosis. It is presumed that changes due to necro-inflammation modify the propagation of shear waves (dispersion). Therefore, new imaging techniques that investigate the dispersion properties of shear waves have been developed, which can serve as an indirect method of measuring liver viscosity (Vi PLUS). Defining the reference values in healthy subjects among different age groups and genders and analyzing the factors that influence these values is essential. However, published data on liver viscosity are still limited. This is the first study that aimed to assess the normal range of liver viscosity values in subjects with healthy livers and analyze the factors that influence them. One hundred and thirty-one consecutive subjects with healthy livers were enrolled in this prospective study. The results showed that Vi PLUS is a highly feasible method. Liver stiffness, age and BMI influenced the liver viscosity values. The mean liver viscosity by Vi PLUS in subjects with healthy livers was 1.59 Pa·s.

A Multidisciplinary Approach to Evaluate the Presence of Hepatic and Cardiac Abnormalities in Patients with Post-Acute COVID-19 Syndrome-A Pilot Study.

(1) Background: Patients suffering from the novel coronavirus 2019 (COVID-19) disease could experience several extra-pulmonary involvements, including cardiovascular complications and liver injury. This study aims to evaluate the presence of cardiac and liver alterations in patients with post-acute COVID-19 syndrome using transthoracic echocardiography (TTE) and liver elastography (LE). (2) Methods: A total of 97 subjects recovering from COVID-19, attending the hospital's specialized outpatient clinic for persisting symptoms at 3 to 11 weeks after the acute illness, were included in this study. They all had a basal COVID-19 assessment, and subsequently, a clinical evaluation, laboratory tests, TTE, and LE. (3) Results: considering the presence of pulmonary injury during COVID-19, patients were divided into two groups. Although none of them had altered systolic function, we evidenced pulmonary hypertension, diastolic dysfunction, increased liver stiffness, viscosity, and steatosis in around one-third of the patients, with significantly higher values in subjects with pulmonary injury compared to those without. (4) Conclusion: persisting symptoms characterizing the post-acute COVID-19 syndrome could be explained by residual cardiac and hepatic lesions, which were worse in more severe COVID-19 forms. These patients may be at risk of developing liver fibrosis and cardiac alterations and should be investigated in the first 12 weeks after the onset of the infection.

Diagnostic Performance of 2-D Shear-Wave Elastography with Propagation Maps and Attenuation Imaging in Patients with Non-Alcoholic Fatty Liver Disease.

We aimed to investigate the diagnostic performance of new 2-D shear-wave elastography (SWE) with propagation maps and attenuation imaging (ATI) for quantification of fibrosis and steatosis in non-alcoholic fatty liver disease (NAFLD). Consecutive patients with NAFLD and healthy volunteers underwent liver stiffness measurement and steatosis quantification by means of vibration-controlled transient elastography coupled with the controlled attenuation parameter as the reference and by 2-D shear-wave elastography (2-D-SWE) with propagation maps and ATI as the investigational methods. We included 232 participants (164 in the NAFLD group and 68 in the healthy control group): 51.7%/49.3% women/men; mean age, 54.2 ± 15.2 y; mean body mass index, 29.4 ± 6.5 kg/m2. Significant correlations were found between 2-D-SWE and vibration-controlled transient elastography (r = 0.71, p < 0.0001) and between ATI and the controlled attenuation parameter (r = 0.72, p < 0.0001). NAFLD-specific 2-D-SWE liver stiffness measurement cutoffs were as follows-F ≥ 2: 7.9 kPa (area under the curve [AUC] = 0.91); F ≥ 3: 10 kPa (AUC = 0.92); and F = 4: 11.4 kPa (AUC = 0.95). For steatosis, the best cutoffs by ATI were as follows-S1 = 0.73 dB/cm/MHz (AUC = 0.86); S2 = 0.76 dB/cm/MHz (AUC = 0.86); and S3 = 0.80 dB/cm/MHz (AUC = 0.83). According to Baveno VI criteria, the optimal 2-D-SWE liver stiffness measurement for diagnosing liver cirrhosis is 15.5 kPa (AUC = 0.94), and for ruling out compensated advanced chronic liver disease it is 9.2 kPa (AUC = 0.92). To conclude, 2-D-SWE with propagation maps and ATI is reliable for quantification of liver fibrosis and steatosis in patients with NAFLD.

Quantification of Liver Fibrosis, Steatosis, and Viscosity Using Multiparametric Ultrasound in Patients with Non-Alcoholic Liver Disease: A "Real-Life" Cohort Study.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. This study aimed to evaluate the performance of four ultrasound-based techniques for the non-invasive multiparametric (MPUS) assessment of liver fibrosis (LF), steatosis (HS), and inflammation in patients with NAFLD. We included 215 consecutive adult patients with NAFLD (mean age: 54.9 ± 11.7; 54.5% were male), in whom LF, HS, and viscosity were evaluated in the same session using four new ultrasound-based techniques embedded on the Aixplorer MACH 30 system: ShearWave Elastography (2D-SWE.PLUS), Sound Speed Plane-wave UltraSound (SSp.PLUS), Attenuation Plane-wave UltraSound (Att.PLUS), and Viscosity Plane-wave UltraSound (Vi.PLUS). Transient Elastography (TE) with Controlled Attenuation Parameter (CAP) (FibroScan) were considered as control. All elastographic measurements were performed according to guidelines. Valid liver stiffness measurements (LSM) were obtained in 98.6% of patients by TE, in 95.8% of patients by 2D-SWE.PLUS/Vi.PLUS, and in 98.1% of patients by Att.PLUS/SSp.PLUS, respectively. Therefore, 204 subjects were included in the final analysis. A strong correlation between LSMs by 2D-SWE.PLUS and TE (r = 0.89) was found. The best 2D-SWE.PLUS cut-off value for the presence of significant fibrosis (F ≥ 2) was 7 kPa. Regarding steatosis, SSp.PLUS correlated better than Att.PLUS with CAP values: (r = -0.74) vs. (r = 0.45). The best SSp.PLUS cut-off value for predicting the presence of significant steatosis was 1524 m/s. The multivariate regression analysis showed that Vi.PLUS values were associated with BMI and LSM by 2D-SWE.PLUS. In conclusion, MPUS was useful for assessing fibrosis, steatosis, and inflammation in a single examination in patients with NAFLD.

Ultrasound-Based Quantification of Fibrosis and Steatosis with a New Software Considering Transient Elastography as Reference in Patients with Chronic Liver Diseases.

The goal of this study was to evaluate the performance of two new ultrasound-based techniques (ShearWave PLUS elastography [2-D-SWE PLUS], SSp PLUS Imaging [SSp PLUS]) implemented on the Aixplorer Mach 30 ultrasound system (Supersonic Imagine, Aix-en-Provence, France) for the non-invasive assessment of liver steatosis and fibrosis, using transient elastography (TE) with the controlled attenuation parameter (CAP) as reference. This monocentric cross-sectional study included 133 consecutive adult patients with chronic hepatopathies. Liver stiffness and steatosis were evaluated in the same session using the techniques mentioned above. An excellent correlation was observed between liver stiffness measurements obtained with 2-D-SWE PLUS and TE (r = 0.92, p < 0.0001). The best cutoff value of 2-D-SWE PLUS for predicting F≥2 was 6.8 kPa; for F≥3, 8.4 kPa; and for F4, 11 kPa. With respect to steatosis evaluation, a strong negative correlation between CAP and SSp PLUS values (r = -0.70, p < 0.0001) was obtained. The best SSp PLUS cutoff value for predicting steatosis was 1537 m/s.

Comparative study between two 2D-Shear Waves Elastography techniques for the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection.

AIMS: We aimed to compare the diagnostic performance of two 2D-Shear Wave Elastography (2D-SWE) techniques for the non-invasive assessment of liver fibrosis in patients with chronic hepatitis C virus (HCV) infection using Transient Elas-tography (TE) as reference. MATERIAL AND METHODS: We enrolled 208 consecutive patients with chronic HCV infection, in which liver stiffness (LS) was evaluated in the same session using two 2D-SWE techniques: 2D-SWE.GE and 2D-SWE.SSI using TE as the method of reference. LS measurements were considered failures when no value was obtained after 10 attempts. RESULTS: Valid LSMs were obtained in 95.6% (199/208) of cases by 2D-SWE.GE, 92.7% (193/208) of cases by 2D-SWE.SSI, and in 94.7% (197/208) of cases by TE (p>0.05). The mean LS values by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI: 10.3±3.8 kPa vs. 15±10.4 kPa (p<0.0001). 2D-SWE.GE LSMs correlated better with TE than 2D-SWE.SSI (r=0.75, p<0.0001 vs. r=0.57, p<0.0001, z test p=0.0012). Linear regression analysis showed a moderate correlation between LSMs obtained by 2D-SWE.GE and 2D-SWE.SSI (r=0.63, R2=0.4, P<0.0001). Pairwise comparison of receiver operating characteristics curves (ROC) found no significant differences between 2D-SWE.GE and 2D-SWE.SSI in identifying F≥2 fibrosis (0.97 vs. 0.96, P = 0.5650), F≥3 (0.97 vs. 0.95, P = 0.2935), or F=4 (0.97 vs. 0.96, p = 0.6914). CONCLUSIONS: Both 2D-SWE techniques had good feasibility for the noninvasive assessment of liver fibrosis. LS values obtained by 2D-SWE.GE were significantly lower than those obtained by 2D-SWE.SSI. No significant differences were found between both methods in staging liver fibrosis in patients with chronic HCV.

Ultrasound-Guided Attenuation Parameter (UGAP) for the quantification of liver steatosis using the Controlled Attenuation Parameter (CAP) as the reference method.

AIM: Nonalcoholic Fatty Liver Disease (NAFLD) is increasing in frequency in daily practice and evaluation of liver steatosis, fibrosis and inflammation severity are essential for prognosis assessment. The aim was to evaluate the usefulnessof a new liver steatosis quantification system - Ultrasound-Guided Attenuation Parameter (UGAP) from General Electric Healthcare, using Controlled Attenuation Parameter (CAP) as the reference method. MATERIAL AND METHOD: 179 consecutive subjects, in whom liver steatosis was assessed in the same session using UGAP, implemented on LOGIQ E10 system (GE Healthcare), and CAP (FibroScan, EchoSens). To discriminate between steatosis stages by CAP, we used the cut-offs recommended by the manufacturer: S1 (mild) - 230 dB/m, S2 (moderate) - 275 dB/m, S3 (severe) - 300 dB/m. RESULTS: We classified our cohort by means of CAP into the following groups: S0 (no steatosis): 48/176 (27.2%), S1 (mild): 56/176 (31.6%), S2 (moderate): 14/176 (7.3%) and S3 (severe): 59/176 (33.9%). The mean UGAP values increased with the steatosis grade and for each group were the following: S0: 198.3±25.7 dB/m, S1: 216.86±26.3 dB/m, S2: 237.79±26.3 dB/m, and S3: 270.8±31.62 dB/m respectively (p<0.001). A very good positive correlation was found between UGAP and CAP values (r=0.73, p<0.0001). The best cut-off values for predicting different grades of liver steatosis using CAP as the reference were: S1 - 192.5 dB/m (AUC 0.83); S2 - 231 dB/m (AUC 0.90) and S3 - 248 dB/m (AUC 0.91). CONCLUSION: UGAP seems to be a good method for liver steatosis quantification and correlates strongly with CAP values.

The Performance of a 2-Dimensional Shear-Wave Elastography Technique for Predicting Different Stages of Liver Fibrosis Using Transient Elastography as the Control Method.

ABSTRACT: The aim was to evaluate the performance of 2-dimensional (2D) shear-wave elastography from general electric (2D SWE-GE), implemented on the new LOGIQ S8 system, for the noninvasive assessment of liver fibrosis, and to identify liver stiffness (LS) cutoff values for predicting different stages of fibrosis using transient elastography (TE) as the control method. We included 179 consecutive subjects, with or without chronic hepatopathies, in whom LS was evaluated in the same session using 2 elastographic techniques: TE (FibroScan, EchoSens) and 2D SWE-GE (LOGIQ S8; GE Healthcare, Chalfont St Giles, United Kingdom). Reliable LS measurements were defined for TE: the median value of 10 measurements with a success rate of 60% or greater and an interquartile range/median ratio (IQR/M) < 0.30; for 2D SWE-GE: the median value of 10 measurements acquired in a homogenous area and IQR/M < 0.30. To discriminate between fibrosis stages by TE, we used the following cutoffs: F2-7; F3-9.5 and F4-12 kPa. Reliable LS measurements were obtained in 97.2% subjects by 2D SWE-GE and in 98.3% by TE (P = 0.72), so that 171 subjects were included for the final analysis. A good correlation was found between the LS values obtained by the 2 methods (r = 0.72, P < 0.0001). The best 2D SWE-GE cutoff value for F ≥ 2 was 6.9 kPa (areas under receiver operating characteristic [AUROC], 0.93; sensitivity, 85.8%; specificity, 90.2%), for F of 3 or greater, it was 8.2 kPa (AUROC, 0.93; sensitivity, 87.5%; specificity, 86.8%) and for F value of 4, it was 9.3 kPa (AUROC, 0.91; sensitivity, 85.7%; specificity, 81.2%). In conclusion, the best 2D SWE-GE (S8) cutoff values for predicting F2, F ≥ 3 and F = 4 were 6.9, 8.2, and 9.3 kPa.

Comparative Study Between the Diagnostic Performance of Point and 2-D Shear-Wave Elastography for the Non-invasive Assessment of Liver Fibrosis in Patients With Chronic Hepatitis C Using Transient Elastography as Reference.

The study compared the diagnostic performance of two shear-wave elastography techniques, elastography point quantification (ElastPQ) and 2-D shear-wave elastography by General Electric (2-D-SWE.GE), for the non-invasive assessment of liver fibrosis in a cohort of patients with chronic hepatitis C virus (HCV) infection, using transient elastography (TE) as the reference method. There was no significant difference between the feasibility rates of TE, ElastPQ and 2-D-SWE.GE (p = 0.507). A good correlation was found between the liver stiffness (LS) values obtained using the two elastographic methods (r = 0.78). The mean LS values obtained using the ElastPQ technique were significantly higher than those obtained using 2-D-SWE.GE (12.1 ± 7.3 kPa vs. 10.4 ± 4.0 kPa, p < 0.0001). Pairwise comparisons of receiver operator characteristics curves between 2-D-SWE.GE and ElastPQ have shown that there are no significant differences in their performance for staging F ≥ 2 fibrosis (p = 0.89), F ≥ 3 fibrosis (p = 0.76) and F = 4 fibrosis (p = 0.86) in patients with chronic HCV infection.

Virtual Touch Quantification using Acoustic Radiation Force Impulse Imaging Technology versus Transient Elastography for the Noninvasive Assessment of Liver Fibrosis in Patients with Chronic Hepatitis B or C using Liver Biopsy as the Gold Standard.

AIMS: Our aim was to assess the diagnostic performance of transient elastography (TE) and Virtual Touch Quantification (VTQ), a point Shear Wave Elastography (pSWE) technique, using Acoustic Radiation Force Impulse (ARFI) technology, for liver fibrosis assessment, as compared to percutaneous liver biopsy (LB), in patients with chronic hepatitis B or C. METHODS: We analyzed 157 patients (80 with chronic hepatitis B and 77 with chronic hepatitis C) with reliable liver stiffness (LS) measurements, in whom we compared TE and VTQ to the LB performed during the same session (evaluated according to the Metavir scoring system: F0-F4). LS was assessed by TE (FibroScan, EchoSens, Paris, France) and VTQ using the Siemens Acuson S2000TM ultrasound system (Siemens AG, Erlangen, Germany). We defined reliable LS measurements as the median value of 10 measurements with an IQR/M <30% for both TE (obtained using the M probe) and VTQ. The areas under receiver operating characteristic curves (AUROCs) were used to assess the diagnostic performance of TE and VTQ. Correlation analysis determined the relationship between LSM values and liver histology. RESULTS: On LB 31 (19.7%) patients had no fibrosis, 35 (22.3%) had F1, 43 (27.4%) had F2, 28 (17.8%) had F3 and 20 (12.7%) had cirrhosis. The mean size of the liver specimen in LB was 27 mm. A strong, linear correlation (Spearman ρ=0.826; p<0.001) with 95% confidence interval for rho (0.769- 0.870), was found between the TE and VTQ measurements. By comparing the AUROC curves, TE and VTQ had similar predictive values for the presence of F≥1 Metavir: AUROC TE=0.876, AUROC VTQ=0.832, p=0.358, for F≥2 Metavir: AUROC TE=0.826, AUROC VTQ=0.862, p=0.313, for F≥3 Metavir: AUROC TE=0.907, AUROC VTQ=0.880, p=0.434 and for F=4 Metavir: AUROC TE=0.981, AUROC VTQ=0.974, p= 0.423. CONCLUSIONS: Both methods, TE and VTQ (pSWE) offer excellent diagnostic accuracy for liver fibrosis assessment in patients with chronic hepatitis B or C with similar performance.

Quantification of Steatosis and Fibrosis using a new system implemented in an ultrasound machine.

AIM: The study compared the usefulness of 2D-SWE and attenuation measurements obtained using Aplio i800 from Canon together with Transient Elastography (TE) and the Controlled Attenuation Parameter (CAP) as the reference method. MATERIAL AND METHODS: We included 112 consecutive adults with reliable LS measurements, 44 healthy subjects and 68 subjects with chronic hepatopathies in whom liver stiffness (LS) and steatosis were evaluated in the same session employing two elastography techniques: Transient Elastography (TE) with Controlled Attenuation Parameter (CAP) implemented on the FibroScan® 530 Compact system and Two Dimensional Shear Wave Elastography (2D-SWE) with Attenuation Imaging (ATI) installed on the Aplio i800 series ultrasound system. Reliable measurements were defined as the median value of 10, respectively 5 valid LS measurements for TE and 2D-SWE, with an interquartile range interval/median ratio (IQR/M) <30%. RESULTS: A very strong positive correlation was found between LS values obtained by TE and 2D-SWE: r=0.88, p<0.0001 and between the attenuation coefficients of steatosis obtained by CAP and ATI, r=0.81, p<0.0001. The best cut-off values by 2DSWE for predicting different stages of liver fibrosis were: for F≥2 - 7.9 kPa and F=4 - 11.7 kPa. Regarding steatosis, the best ATI cut-off values were: for S≥1 - 0.79 dB/cm/mHz and for S3 - 0.86 dB/cm/mHz. CONCLUSION: 2D-SWE and ATI measurements with the new system strongly correlated with TE and CAP results.

Screening for Liver Fibrosis and Steatosis in a Large Cohort of Patients with Type 2 Diabetes Using Vibration Controlled Transient Elastography and Controlled Attenuation Parameter in a Single-Center Real-Life Experience.

BACKGROUND: Type 2 diabetes mellitus (T2DM), obesity, hyperlipidemia, and hypertension are considered risk factors for developing non-alcoholic fatty liver disease (NAFLD). This study aims to assess steatosis and fibrosis severity in a cohort of T2DM patients, using vibration controlled transient elastography (VCTE) and controlled attenuation parameter (CAP). MATERIAL AND METHOD: We performed a prospective study in which, in each patient, we aimed for 10 valid CAP and liver stiffness measurements (LSM). To discriminate between fibrosis stages, we used the following VCTE cut-offs: F ≥ 2-8.2 kPa, F ≥ 3-9.7 kPa, and F4 - 13.6 kPa. To discriminate between steatosis stages, we used the following CAP cut-offs: S1 (mild) - 274 dB/m, S2 (moderate) - 290dB/m, S3 (severe) - 302dB/m. RESULTS: During the study period, we screened 776 patients; 60.3% had severe steatosis, while 19.4% had advanced fibrosis. Female gender, BMI, waist circumference, elevated levels of AST, total cholesterol, triglycerides, blood glucose, and high LSM were associated with severe steatosis (all p-value < 0.05). BMI, waist circumference, elevated levels of AST, HbA1c, and CAP were associated with advanced fibrosis (all p-values < 0.05). CONCLUSION: Higher BMI (obesity) comprises a higher risk of developing severe steatosis and fibrosis. Individualized screening strategies should be established for NAFLD according to different BMI.