Assessing Liver Stiffness by 2-D Shear Wave Elastography in a Healthy Cohort

Performance of 2-D Shear Wave Elastography in Liver Fibrosis Assessment Compared with Serologic Tests and Transient Elastography in Clinical Routine

Bridging the Gap: Screening for Nonalcoholic Fatty Liver Disease in the Primary Care Population

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

Liver stiffness measurement (LSM) is recommended for disease prognostication and monitoring. We evaluated if LSM, using transient elastography, and LSM changes predict decompensation and mortality in patients with alcohol-related liver disease (ALD). We performed an observational cohort study of compensated patients at risk of ALD from Denmark and Austria. We evaluated the risk of decompensation and all-cause mortality, stratified for compensated advanced chronic liver disease (cACLD: baseline LSM ≥10kPa) and LSM changes after a median of 2 years. In patients with cACLD, we defined LSM changes as (A) LSM increase ≥20% ("cACLD increasers") and (B) follow-up LSM <10kPa or <20kPa with LSM decrease ≥20% ("cACLD decreasers"). In patients without cACLD, we defined follow-up LSM ≥10kPa as an LSM increase ("No cACLD increasers"). The remaining patients were considered LSM stable. We followed 536 patients for 3,008 patient-years-median age 57 years (IQR 49-63), baseline LSM 8.1kPa (IQR 4.9-21.7)-371 patients (69%) had follow-up LSM after a median of 25 months (IQR 17-38), 41 subsequently decompensated and 55 died. Of 125 with cACLD at baseline, 14% were "cACLD increasers" and 43% "cACLD decreasers", while 13% of patients without cACLD were "No cACLD increasers" (n= 33/246). Baseline LSM, follow-up LSM and LSM changes accurately predicted decompensation (C-index: baseline LSM 0.85; follow-up LSM 0.89; LSM changes 0.85) and mortality (C-index: baseline LSM 0.74; follow-up LSM 0.74; LSM changes 0.70). When compared to "cACLD decreasers", "cACLD increasers" had significantly lower decompensation-free survival and higher risks of decompensation (subdistribution hazard ratio 4.39, p= 0.004) and mortality (hazard ratio 3.22, p= 0.01). LSM by transient elastography predicts decompensation and all-cause mortality in patients with compensated ALD both at diagnosis and when used for monitoring. Patients at risk of alcohol-related liver disease (ALD) are at significant risk of progressive disease and adverse outcomes. Monitoring is essential for optimal disease surveillance and patient guidance, but non-invasive monitoring tools are lacking. In this study we demonstrate that liver stiffness measurement (LSM), using transient elastography, and LSM changes after a median of 2 years, can predict decompensation and all-cause mortality in patients at risk of ALD with and without compensated advanced chronic liver disease. These findings are in line with results from non-alcoholic fatty liver disease, hepatitis C and primary sclerosing cholangitis, and support the clinical utility of LSM, using transient elastography, for disease prognostication and monitoring in chronic liver diseases including ALD, as recommended by the Baveno VII.

Reply to: Correspondence on “EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update”

See the Original "The usefulness of non-invasive liver stiffness measurements in predicting clinically significant portal hypertension in cirrhotic patients: Korean data" on page 370.

BackgroundPreventing disease progression and viral suppression are the main goals of antiviral therapy in chronic hepatitis B (CHB). Liver stiffness measurement (LSM) by transient elastography is a reliable non-invasive method to assess liver fibrosis in patients with CHB. Our aim was to explore factors that may affect changes in LSMs during long term tenofovir (TDF) monotherapy in a well characterized cohort of patients with compensated CHB.MethodsWe analyzed serial LSMs in 103 adult patients with CHB who were on TDF monotherapy and had at least three LSMs over a period of 90 months.ResultsTwenty-five (24%) patients had advanced fibrosis at baseline. A significant decline in mean LSM between baseline and last visit (8.7 ± 6.2 kPa vs. 6.7 ± 3.3, p = 10− 3) was observed. Twenty-four (23%) patients had progression of liver fibrosis with mean increase in liver stiffness of 2.8 kPa (range: 0.2–10.2 kPa). Multivariate analysis showed that BMI ≥ 25 (OR, 0.014; 95% CI, 0.001–0.157; p = 0.001) and advanced fibrosis (OR, 5.169; 95% CI, 1.240–21.540; p = 0.024) were independently associated with a fibrosis regression of > 30% of liver stiffness compared to baseline value.ConclusionsIn CHB patients TDF monotherapy resulted in liver fibrosis regression, especially in patients with advanced fibrosis. Despite the successful antiviral effect of TDF, 1 out of 4 patients had liver fibrosis progression. Obesity and advanced fibrosis at baseline were independently associated with significant liver fibrosis regression.

Background Hepatitis C virus (HCV) is a major cause of chronic liver disease, in which liver stiffness increases. Liver stiffness measurements (LSM) are therefore essential in diagnosing liver diseases and predicting disease development. The study objective was to perform a comprehensive prospective assessment of the liver before, after and 4 years after treatment for HCV, including an assessment of the long-term outcome of fibrosis, steatosis and inflammation. Methods and findings Patients eligible for HCV treatment were included prospectively in 2018 (n = 47). Liver stiffness was measured using transient elastography and 2D shear-wave elastography (SWE). Blood tests, B-mode ultrasound (US) and SWE, were performed before, after (end of treatment [EOT]), 3 months after (EOT3) and 4 years after treatment (4Y). At the final visit, we added attenuation imaging and shear-wave dispersion slope (SWDS) measurements to assess steatosis and inflammation. Three months after treatment, the sustained virologic response rate was 93%. The median liver stiffness for baseline, EOT, EOT3 and 4Y was 8.1, 5.9, 5.6 and 6.3 kPa, respectively. There was a significant reduction in liver stiffness from baseline to EOT, and from EOT to EOT3. After 4 years, the mean attenuation coefficient (AC) was 0.58 dB/cm/MHz, and the mean SWDS value was 14.3 (m/s)/kHz. Conclusion The treatment for HCV was highly effective. Measurements of liver stiffness decreased significantly after treatment and remained low after 4 years. AC measurements indicated low levels of liver steatosis. Shear-wave dispersion values indicated inflammation of the liver, but the clinical implication is undetermined and should be explored in larger studies. Clinicaltrials.gov: NCT03434470 Abbreviations AC: attenuation coefficient; APRI: aspartate aminotransferase to platelet ratio index; ATI: attenuation imaging; cACLD: compensated advanced chronic liver disease; CAP: controlled attenuation parameter; FIB-4: Fibrosis-4 Index for liver fibrosis; HCC: hepatocellular carcinoma; LSM: liver stiffness measurement; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; SWDS: shear-wave dispersion slope; SWE: shear-wave elastography; US: ultrasound

P1094 FIBROSIS REGRESSION IN PERSONS TREATED FOR HBV UTILIZING TRANSIENT ELASTOGRAPHY (FIBROSCAN)

Introduction: Non-invasive Liver fibrosis evaluation in suspected NAFLD has been studied in obese adults, but few studies have addressed the utility of Transient and Shear-wave Elastography assessing early-stage fibrosis in pediatric population. We aimed to perform a systematic review and meta-analysis to compare Liver Elastography findings between obese and non-obese children. Methods: PubMed, MEDLINE (OVID), Cochrane Library, Embase, Scopus and Web of Science were searched from inception to January 2022 to identify manuscripts that evaluated Liver steatosis/Liver fibrosis on Elastography (Transient or Shear-wave) in obese children compared to non-obese children. Case series, case reports, editorials, and reviews were excluded. Two independent reviewers extracted data. Disagreements were resolved by a third author. Meta-analyses were performed using a random-effect model with the inverse variance method. We used the Paule-Mandel estimator and Hartung-Knapp-Sidik-Jonkman method for τ2 and 95% confidence intervals calculation. For continuous outcomes we used the Mean Difference (MD). Heterogeneity was assessed by the inconsistency index (I2). Results: Among 3182 articles identified, 17 studies were identified for full text review. Five studies were deemed eligible for inclusion with perfect agreement between investigators (kappa=1.0). A total of 296 obese children and 528 non-obese controls were included in the studies (Table). Three studies used Shear-wave Elastography, four used Transient Elastography and one used both. The female proportion was higher in the non-obese group. ALT and AST values were higher in the obese group in most of the studies. On the non-stratified meta-analysis obese children were found to have higher values of Liver Stiffness Measurement (LSM) measured in kilopascals (kPa) compared with non-obese controls (MD: 1.80, 95% CI: 0.27 - 3.34), however, when stratifying this effect was only significant when using only Transient Elastography (MD: 1.49, 95%: 0.16 - 2.82) (Figure). Conclusion: Our systematic review and meta-analysis demonstrates that obese children present higher values of Liver Stiffness compared to non-obese children. In that sense, this non-invasive testing could be successfully applied as a predictor of NAFLD in the clinical setting. These findings may depend on the elastography type, since it was significant using the Transient Elastography, and more studies are needed to further validate this non-invasive testing.Figure 1.: Forest plot of the effect in Liver stiffness Measurement (kPa) Table 1. - Baseline Characteristics of Included Subjects Study Group Sample size Age (years) Female % ALT AST Total Cholesterol Triglycerides Saglam (2021) Obese 41 11.4 (9.6-13.5) 46.3% 18 (15-22) 21 (19-23) 156 (142-172.75) mg/dl 107.5 (87-135.5) mg/dl Non-obese 25 11.7 (9-13.2) 52% 13 (10.1-16.2) 23 (17.7-25.3) 137.5 (128-149.75) mg/dl 68 (59.25-98.25) mg/dl Zeng Fansen (2020) Obese 67 10.9 (6-17.4) 28.4% 59 (23-101) 32 (21-58) 4.7 (4.3-5.7) mmol/L 1.4 (0.9-1.9) mmol/L Non-obese 139 10.2 (5-17) 41.7% 19 (15-25) 27 (16-34) 3.1 (2.8-3.3) mmol/L 1.1 (0.8-1.3) mmol/L Mărginean (2019) Obese 77 10.4 ± 3.4 33.7% 26.50 ± 43.1 27.33 ± 23.6 NA NA Non-obese 210 11.3 ± 3.83 54.8% 13.64 ± 6.9 22.29 ± 10.9 NA NA Kwon (2019) Obese 59 10.9 ± 2.4 38% 91.27 ± 97.7 57.00 ± 48.5 173.97 ± 37.23 mg/dl NA Non-obese 47 10.1 ± 2.8 40% 16.28 ± 9.8 26.40 ± 11.8 146.65 ± 59.07 mg/dl NA Cho Y (2015) Obese 52 13.0 (3.5-17.6) 26.9% 75 ± 83 48 ± 45 NA 149 ± 73 mg/dl Non-obese 107 11.2 (1.3-17) 49.5% 17 ± 14 24 ± 7 NA 97 ± 65 mg/dl

PurposeThe first aim of this study was to analyze the relationships between liver stiffness measurement, hepatic venous pressure and liver fibrosis. The second aim was to demonstrate the utility of real-time shear wave elastography for evaluation of Budd-Chiari syndrome patients before and after balloon hepatic venous angioplasty.Materials and methodsA total of 32 patients with Budd-Chiari syndrome slated for successful balloon angioplasty met the inclusion and exclusion criteria. Shear wave elastography was used to generate dynamic liver stiffness measurement 2 days before angioplasty and 2 days, 3 months, and 6 months after angioplasty. Hepatic venous pressures were measured during balloon angioplasty. Correlations among liver stiffness, hepatic venous pressure, and fibrosis were assessed.ResultMean liver stiffness was 35.17 ± 10.60 kPa, 20.15 ± 5.47 kPa, 15.36 ± 4.34 kPa and 15.68 ± 5.58 kPa at baseline and 2 days, 3 months, and 6 months after angioplasty, respectively. Liver stiffness measured at 2 days and 3 months after angioplasty was significantly decreased (P < 0.001); liver stiffness measured at 6 months after angioplasty was not significantly different from that measured at 3 months after angioplasty (P = 0.636). Analysis of liver stiffness measurement and hepatic venous pressure before balloon angioplasty yielded a coefficient of correlation r = 0.701 (P < 0.001). Before and 2d after angioplasty, liver stiffness measurement did not correlated with fibrosis (r = − 0.170, P = 0.22), (r = 0.223, P = 0.220), respectively, while the LSM difference before and 2 days after angioplasty negatively correlated with stiffness severity (r = − 0.502, P = 0.003). Liver stiffness measured at 2 days and 3 months after angioplasty was significantly decreased (P < 0.001), remaining stable at 3 months, though still in the cirrhotic range.ConclusionsThe liver stiffness of Budd-Chiari syndrome patients, measured by shear wave elastography, decreased considerably after hepatic venous recanalization, and significantly correlated with hepatic venous pressure though not with degree of fibrosis. Shear wave elastography may be effective in monitoring short- and long-term treatment outcomes in Budd-Chiari syndrome.

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.

Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals

Ultrasound Shear Wave Elastography for Liver Disease. A Critical Appraisal of the Many Actors on the Stage.

ObjectiveThis study aimed to explore the predictive value of liver and spleen stiffness measurement based on two-dimensional shear wave elastography for the portal vein pressure in patients with compensatory viral cirrhosis.MethodsFrom January 2017 to August 2019, 107 patients with compensatory viral cirrhosis and 76 patients with viral hepatitis were enrolled as cirrhosis group and hepatitis group, respectively. Patient data were obtained during admission, and this study was a review and analysis of patient data. Liver stiffness measurement (LSM), spleen stiffness measurement (SSM), portal vein diameter and spleen thickness were compared between the two groups, and their diagnostic value for compensatory viral cirrhosis was analyzed. According to the hepatic vein pressure, the cirrhosis group patients were divided into non-hypertensive group (no portal hypertension, hepatic venous pressure gradient (HVPG) < 5 mmHg), mild group (mild portal hypertension, 5 mmHg ≤ HVPG ≤ 10 mmHg) and severe group (clinically significant portal hypertension group, HVPG > 10 mmHg). LSM, SSM, portal vein diameter and spleen thickness of the three groups were compared, and the correlation between SSM and hepatic vein pressure was analyzed.ResultsLSM, SSM, portal vein diameter and spleen thickness in the cirrhosis group were higher than those in hepatitis group (all P < 0.05). The area under the curve (AUC) of combined detection was larger than that of LSM, SSM and spleen thickness detection alone in liver cirrhosis diagnosis (all P < 0.05). LSM, SSM, portal vein diameter and spleen thickness increased with the increase of hepatic vein pressure in patients with liver cirrhosis (all P < 0.05). LSM, SSM, portal vein diameter and spleen thickness were all positively correlated with hepatic vein pressure (P < 0.05). ROC curve showed that AUC of combined detection was greater than that of LSM, SSM, portal vein diameter and spleen thickness alone detection in the diagnosis of clinically significant portal hypertension (all P < 0.05). The increase of LSM, SSM, portal vein diameter and spleen thickness were the influencing factors for hepatic vein pressure rising (all P < 0.05).ConclusionThere was an increase of LSM and SSM in patients with compensatory viral cirrhosis, which were positively correlated with hepatic venous pressure, and combined index detection has diagnostic and predictive value for the change of portal venous pressure.