Liver Stiffness Values Research Articles

Liver fibrosis is associated with left ventricular remodeling: insights into the liver-heart axis

Abstract Background Non-alcoholic fatty liver disease (NAFLD), common in type 2 diabetes, has emerged as an important and independent risk factor for adverse cardiac remodeling. Fibrosis in the liver could be a key factor in this relationship. Despite the fact that NAFLD is a long-term progressive disease, imaging studies on this topic are mainly limited to selected patients from tertiary centres. Purpose To investigate the relationship between liver fat, liver fibrosis and cardiac remodeling in the general population. We also sought to explore biomarkers of cardiovascular inflammation and fibrosis, for possible mechanistic pathways in these relationships. Methods We included 46 participants with type 2 diabetes and 46 age and sex-matched controls (overall 35%/65% F/M, mean age 59.5 ± 4.6), all randomly sampled from the general population. Participants underwent careful clinical phenotyping, including blood sampling, echocardiography, and magnetic resonance imaging (MRI) at 1.5 T. The MRI protocol included sequences for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography at 56 Hz), left ventricular (LV) structure, function, and tissue characteristics (native T1 mapping). We also analyzed ∼290 circulating cardiovascular biomarkers. A Bayesian statistical approach (‘Stochastic Search Variable Selection’) was used to identify the biomarkers most strongly associated with cardiac remodeling. Results For liver stiffness, the mean value was 2.1 ± 0.4 kPa and the highest value was 2.9 kPa. The median liver fat value was 5.7% (IQR 9.9%) and 53 participants (58%) displayed hepatic steatosis (liver fat > 5%). LV concentricity increased across quartiles of liver stiffness (P=0.0014 for ANOVA), while LV concentricity and diastolic dysfunction increased across quartiles of liver fat (P=0.0023 and P=0.030 for ANOVA, respectively). Myocardial T1 displayed no relationships to neither liver fat nor liver stiffness. In a multiple linear regression, liver stiffness was positively associated with LV concentricity (Beta=0.26, P=0.0053), independently of diabetes and liver fat. This association was attenuated (Beta=0.17, P=0.077) when adjusting for circulating levels of IL-1 receptor type 2, the biomarker with the strongest association to LV concentricity in the Bayesian statistical analysis. Conclusion In our well-characterized subjects from the general population, we found that a majority had hepatic steatosis but overall rather low liver stiffness values. Despite this, liver stiffness was related to increased LV concentricity independently of liver fat and diabetes. This association was attenuated when also adjusting for IL-1 receptor type 2. Our results suggest a link between liver fibrosis and cardiac remodeling also in the early stages of fatty liver disease, possibly involving the IL-1 signaling pathway. Future studies are needed to further establish causality and potential mechanisms.Multiple linear regression analysesLiver magnetic resonance elastogram

Clinical application of two dimensional shear wave elastography with a propagation map in evaluating liver fibrosis in patients with liver tumors.

This study aimed to evaluate the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) with a propagation map in evaluating the degree of hepatic fibrosis in patients with liver tumors before resection. From January 2020 to April 2021, 128 patients with liver tumors were prospectively enrolled, including 20 benign liver tumors and 108 malignant liver tumors. 2D-SWE with a propagation map technology was used to measure the stiffness of liver parenchyma 2 cm away from the tumor. The median value of five measurements was used in this study. The stage of hepatic fibrosis was graded in accordance with Scheuer standard. Spearman correlation was used to analyze the correlation between liver fibrosis stage and the liver stiffness. Univariate and multivariate linear regression analyses were used to determine significant affecting factors for liver stiffness value. The diagnostic performance of 2D-SWE with a propagation map in predicting fibrosis stage was evaluated by receiver operating characteristic curve analysis. The median liver stiffness value in patients with benign liver tumors was lower than that in patients with malignant liver tumors (6.0 kPa vs. 9.4 kPa, p < 0.05). The median liver stiffness values in patients with primary liver cancer were higher than that in patients with benign liver tumors and other types of malignant liver tumors (9.6 kPa vs. 6.0 kPa, p < 0.05). The liver stiffness measured by 2D-SWE was highly correlated with the fibrosis stage confirmed by postoperative pathology (r = 0.834, p < 0.05). For the liver stiffness value, PLT,TB,ALB and fibrosis stage are significantly associated with liver stiffness. The median liver stiffness values in stages S0-S4 of fibrosis were 6.0, 7.2, 8.0, 9.4, and 12.6 kPa, respectively. The areas under the ROC curve of S≥1, S≥2, S≥3, and S = 4 as predicted by SWE were 0.932, 0.945, 0.945, and 0.916, respectively. According to the Youden index, the optimal critical values for predicting fibrosis S≥1, S≥2, S≥3, and S = 4 were 6.8 (sensitivity of 89.69% and specificity of 93.55%), 7.5 (sensitivity of 87.50 % and specificity of 95.00 %), 8.3 (sensitivity of 87.14 % and specificity of 87.93 %) and 9.8 (sensitivity of 79.55 % and specificity of 86.90 %) kPa. 2D-SWE with a propagation map could noninvasively and accurately predict the staging of liver fibrosis in patients with liver tumors before resection.

Determinants of Advanced Liver Fibrosis in Adult Patients After Fontan Palliation: Usefulness of Ultrasound Transient Elastography.

Fontan-associated liver disease is an increasing concern. Our aim was to assess prevalence and predictors of advanced liver fibrosis with a specific focus on utility of liver stiffness measurement by ultrasound transient elastography. A total of 97 adult Fontan patients (55% male, median age: 23.1 years, interquartile range [IQR]: 18.7-30.6); 92 (95%) were evaluated with transient elastography, and 50 (52%) underwent transjugular liver biopsy. Advanced liver fibrosis was defined as congestive hepatic fibrosis score 3 or4. Only 4 patients (4%) had liver stiffness values < 10 kilopascal (kPa). Liver-stiffness measurements correlated weakly with peak oxygen uptake on exercise testing and Fontan pressure but not with Model for End-Stage Liver Disease excluding INR (MELD-XI) score or spleen size. Serial follow-up liver stiffness measurements in 73 clinically stable patients showed large variability among individual patients. Advanced liver fibrosis was present in 35 of 50 (70%) patients on liver biopsy and was associated to MELD-XI-Score ≥ 11 and splenomegaly but not to liver-stiffness measurements. Advanced liver fibrosis was not associated with patient age or time since Fontan operation but with younger age at completion of Fontan (3.7 years, IQR: 2.3-6.3 vs 6.8 years; IQR: 3.5-12.1; P= 0.037). In our cohort, advanced liver fibrosis was present in the majority of adult Fontan patients. Liver stiffness as measured by transient elastography was not associated with the degree of liver fibrosis. Because of its high variability on serial measurements, it seems not to be useful for clinical decision making. The unexpected finding that younger age at completion of Fontan was associated with advanced liver fibrosis merits further evaluation.

Stiffness on shear wave elastography as a potential microenvironment biomarker for predicting tumor recurrence in HBV-related hepatocellular carcinoma

BackgroundTo explore the pathologic basis and prognostic value of tumor and liver stiffness measured pre-operatively by two-dimensional shear wave elastography (2D-SWE) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients who undergo hepatic resection.MethodsA total of 191 HBV-infected patients with solitary resectable HCC were prospectively enrolled. The stiffness of intratumoral tissue, peritumoral tissue, adjacent liver tissue, and distant liver tissue was evaluated by 2D-SWE. The correlations between stiffness and pathological characteristics were analyzed in 114 patients. The predictive value of stiffness for recurrence-free survival (RFS) was evaluated, and Cutoff Finder was used for determining optimal cut-off stiffness values. Cox proportional hazards analysis was used to identify independent predictors of RFS.ResultsPathologically, intratumoral stiffness was associated with stroma proportion and microvascular invasion (MVI) while peritumoral stiffness was associated with tumor size, capsule, and MVI. Adjacent liver stiffness was correlated with capsule and liver fibrosis stage while distant liver stiffness was correlated with liver fibrosis stage. Peritumoral stiffness, adjacent liver stiffness, and distant liver stiffness were all correlated to RFS (all p < 0.05). Higher peritumoral stiffness (> 49.4 kPa) (HR = 1.822, p = 0.023) and higher adjacent liver stiffness (> 24.1 kPa) (HR = 1.792, p = 0.048) were significant independent predictors of worse RFS, along with tumor size and MVI. The nomogram based on these variables showed a C-index of 0.77 for RFS prediction.ConclusionsStiffness measured by 2D-SWE could be a tumor microenvironment and tumor invasiveness biomarker. Peritumoral stiffness and adjacent liver stiffness showed important values in predicting tumor recurrence after curative resection in HBV-related HCC.Clinical relevance statementTumor and liver stiffness measured by two-dimensional shear wave elastography serve as imaging biomarkers for predicting hepatocellular carcinoma recurrence, reflecting biological behavior and tumor microenvironment.Key points• Stiffness measured by two-dimensional shear wave elastography is a useful biomarker of tumor microenvironment and invasiveness.• Higher stiffness indicated more aggressive behavior of hepatocellular carcinoma.• The study showed the prognostic value of peritumoral stiffness and adjacent liver stiffness for recurrence-free survival.• The nomogram integrating peritumoral stiffness, adjacent liver stiffness, tumor size, and microvascular invasion showed a C-index of 0.77.Graphical

The Prevalence of Liver Fibrosis Stages on More than 23,000 Liver Stiffness Measurements by Vibration-Controlled Transient Elastography: A Single Center Study.

Vibration-controlled transient elastography (VCTE) was the first non-invasive method used for assessing liver fibrosis in patients with chronic liver disease. Over the years, many studies have evaluated its performance. It is now used globally, and, in some countries, it represents the primary step in evaluating liver fibrosis. The aim of this study is to assess the feasibility of VCTE and highlight the prevalence of liver fibrosis stages assessed by VCTE in a large cohort of patients at a single study center. We also aimed to observe the trends in liver stiffness (LS) values over the years according to each type of hepatopathy. A retrospective study was conducted over a period of 13 years (2007-2019) and included patients who presented to our clinic for LS measurements (LSMs), either with known liver diseases or with suspected liver pathology who were undergoing fibrosis screening. The database contained a total of 23,420 measurements. Valid LSMs were obtained in 90.91% (21,291/23,420) of the cases, while 2129 (9.09%) of the measurements were either failed or unreliable. In untreated patients with chronic viral hepatitis, LS values tended to increase during the years, while in patients undergoing antiviral therapy LS values significantly decreased. Our comprehensive study, one of the largest of its kind spanning 13 years, emphasizes the reliability and significance of VCTE in real-world clinical settings.

Hepatic Involvement across the Metabolic Syndrome Spectrum: Non-Invasive Assessment and Risk Prediction Using Machine Learning.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) and metabolic syndrome (MetS) are inextricably linked conditions, both of which are experiencing an upward trend in prevalence, thereby exerting a substantial clinical and economic burden. The presence of MetS should prompt the search for metabolic-associated liver disease. Liver fibrosis is the main predictor of liver-related morbidity and mortality. Non-invasive tests (NIT) such as the Fibrosis-4 index (FIB4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), hepatic steatosis index (HIS), transient elastography (TE), and combined scores (AGILE3+, AGILE4) facilitate the detection of liver fibrosis or steatosis. Our study enrolled 217 patients with suspected MASLD, 109 of whom were diagnosed with MetS. We implemented clinical and biological evaluations complemented by transient elastography (TE) to discern the most robust predictors for liver disease manifestation patterns. Patients with MetS had significantly higher values of FIB4, APRI, HSI, liver stiffness, and steatosis parameters measured by TE, as well as AGILE3+ and AGILE4 scores. Machine-learning algorithms enhanced our evaluation. A two-step cluster algorithm yielded three clusters with reliable model quality. Cluster 1 contained patients without significant fibrosis or steatosis, while clusters 2 and 3 showed a higher prevalence of significant liver fibrosis or at least moderate steatosis as measured by TE. A decision tree algorithm identified age, BMI, liver enzyme levels, and metabolic syndrome characteristics as significant factors in predicting cluster membership with an overall accuracy of 89.4%. Combining NITs improves the accuracy of detecting patterns of liver involvement in patients with suspected MASLD.

Liver parenchymal changes detected by MR elastography and diffusion-weighted imaging after stereotactic body radiotherapy for hepatocellular carcinoma.

Stereotactic body radiotherapy (SBRT) is a local treatment option for hepatocellular carcinoma (HCC). SBRT-induced focal reactions on the liver parenchyma have not been thoroughly evaluated using quantitative magnetic resonance imaging (MRI). To quantitatively evaluate liver parenchymal changes caused by SBRT for HCC using magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI). We retrospectively evaluated 22 adult patients who received SBRT for HCC and 27 who received locoregional therapy other than SBRT (controls). Liver stiffness by MRE and apparent diffusion coefficient (ADC) values by DWI of the liver parenchyma were measured before and after SBRT. Regions of interest (ROIs) were drawn on the two areas of radiation dose distribution levels, > 30 Gy and ≤ 30 Gy; a ROI was drawn in the control group. The two indices were compared before and after SBRT using a Wilcoxon matched-pairs signed-rank test. Liver stiffness and ADC values were significantly increased after SBRT in the dose areas of > 30 Gy compared with those before SBRT (4.05 vs 4.85 kPa; p < 0.05 in liver stiffness, and 1.10 vs 1.40 ×10-3 s/mm2; p < 0.05 in ADC values). In the dose area of ≦ 30 Gy, liver stiffness showed a significant increase in one reader (p = 0.033) but not in another reader (p = 0.085); ADC value showed no significant difference before and after SBRT as per both readers (p > 0.05). The control group demonstrated no significant differences before and after treatment (p > 0.05). MRE and DWI can be used to detect SBRT-induced liver parenchymal changes.

Diagnostic Performance of Quantitative Ultrasound Parameters in Non-alcoholic Fatty Liver Disease

Marked liver steatosis, steatohepatitis, and significant fibrosis are risk factors for unfavorable outcomes in non-alcoholic fatty liver disease (NAFLD). In this study, the diagnostic performance ofattenuation coefficient(AC), liver stiffness(LS), and dispersion slope (DS) was evaluated separately and combined in the diagnosis of liver steatosis and fibrosis in NAFLD suspects using biopsy or magnetic resonance imaging (MRI) as a reference standard. Seventy-four NAFLD suspects were prospectively imaged with an Aplio i800 ultrasound scanner (Canon Medical Systems, Tustin, CA). AC, LS, and DS measurements were obtained from the right liver lobe. Thirty-four patients underwent liver biopsy, and 40 had MRI. There were 32 patients (43%) with liver steatosis and fibrosis (S+F), 22(30%) with steatosis (S), 5 (7%) with fibrosis (F), and 15 (20%) with normal liver (N). Mean ACs were significantly higher in steatotic livers (n=54) than in non-steatotic livers (n=20) (P<0.0001). LS and DS were significantly higher in patients with liver fibrosis (n=37) compared tonon-fibrotic livers (n=37) (P=0.0004 and P=0.0002, respectively). In detecting (S+F), the area under the receiver operating characteristic curve (AUROCC) was 0.87 for combined ultrasound parameters of LS and AC (negative predictive value [NPV]: 75%, positive predictive value [PPV]: 77%, P<0.0001). In detecting patients with liver steatosis and fibrosis stage ≥2, LS had an AUROCC of 0.93 (NPV: 87%, PPV: 82%, P<0.0001). In the biopsy group, 32% (11/34) were diagnosed with non-alcoholic steatohepatitis (NASH). DS values showed a significant difference among patients with (n=23) or without (n=11) hepatocellular ballooning (P=0.02). AUROCC was 0.87 for combined ultrasound parameters of AC, LS, and DS with body mass index (BMI) in detecting NASH (NPV: 80%, PPV: 87%, P=0.0006). AC and LS showed high diagnostic value in detecting liver steatosis and fibrosis, respectively. The combined AC and LS values further improved the diagnostic accuracy in detecting NAFLD and high-risk NAFLD patients.

Impact of Chronotype and Mediterranean Diet on the Risk of Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease.

Late chronotype, the individual's aptitude to perform daily activities late in the day, has been associated with low adherence to the Mediterranean diet (MedDiet) and metabolic syndrome. The aim of this work was to investigate the potential association of chronotype and adherence to the MedDiet with the liver fibrosis risk in patients with non-alcoholic fatty liver disease (NAFLD). Liver stiffness was assessed in 126 patients by FibroScan®530. Significant (F ≥ 2) and advanced (F ≥ 3) hepatic fibrosis were defined according to liver stiffness values ≥7.1 kPa and ≥8.8 kPa, respectively. Chronotype (MSFsc) was defined by the Munich Chronotype Questionnaire, and adherence to the MedDiet was defined by the Mediterranean diet score (MDS). Overall, the median age was 55 (46-63) years, and 57.9% of participants were male. The principal comorbidities were type-2 diabetes mellitus (T2DM) (26.1%), arterial hypertension (53.1%), dyslipidaemia (63.4%), obstructive sleep apnoea (5.5%) and depression (5.5%). Most subjects (65.0%) had intermediate + late chronotype and showed higher mid-sleep on workdays (p < 0.001) and on work-free days (p < 0.001) compared to those with early chronotype. In the logistic regression model, intermediate + late chronotype (p = 0.024), MDS (p = 0.019) and T2DM (p = 0.004) were found to be significantly and independently associated with the risk of both F ≥ 2 And F ≥ 3. We observed that the intermediate + late chronotype and low adherence to the MedDiet were associated with both significant and advanced liver fibrosis in patients with NAFLD.

Evaluation of hepatic fibrosis by transient elastography in βthalassemia children before and after hematopoietic stem cell transplantation

Abstract Background Iron overload is a major concern in all patients with transfusion-dependent thalassemia (TDT). The liver, being a target for iron deposition is at risk of developing liver fibrosis or even cirrhosis. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment in clinical practice, a process that is surrounded by several precautions and complications that may affect the liver condition as well. Aim To evaluate the degree of hepatic fibrosis in children with TDT before and after HSCT. Methodology Twenty-five children with TDT who underwent HSCT were investigated by serum ferritin in addition to the assessment of liver fibrosis using transient elastography by FibroScan and liver fibrosis scores before and 1-year after HSCT. Results Out of the 25 children enrolled, only 16 completed a 1-year post-transplantation follow-up period. Slightly increased liver stiffness values measured by FibroScan 1-year post-transplantation, but the patients were still having the same degree of fibrosis of the pre-transplant period. FIB-4 score and APRI also showed statistically significant increase post-transplant as compared to pre-transplantation. Conclusion Stationary degree of fibrosis in thalassaemic children after HSCT with slight increases in the liver stiffness values by transient elastography that necessitates longer follow-up of the fibrosis status of patients’ post-transplant. Transient elastography is considered a helpful noninvasive tool for assessment of the hepatic status before and after HSCT.

Outcome of direct-acting antiviral treatment in patients with hepatitis C virus/hepatitis B virus coinfection

BackgroundOral direct-acting antiviral (DAA) regimens for chronic hepatitis C virus (HCV) infection have greatly improved treatment efficacy, with sustained virological response (SVR) rates of > 95% for HCV monoinfected patients. However, hepatitis B virus (HBV)/HCV coinfection is more complex than monoinfection with HBV or HCV alone. We evaluated the SVR rate at 12 weeks post-treatment with DAAs in patients with HCV/HBV and evaluated the rate of HBV reactivation during and 6 months after treatment.ResultsAmong the included patients, 191 (95.5%) achieved SVR. Older age, low platelet count, high serum creatinine, and higher liver stiffness value measured by fibroscan were predictors of failure to achieve SVR. The 16 patients (8%) with HBV reactivation patients had significantly higher ALT and serum creatinine and a high HCV RNA viral load at baseline compared with that of those without HBV reactivation.ConclusionPatients who received DAAs to treat HCV/HBV coinfection showed a high SVR. However, it is important to be aware of the potential risk for HBV reactivation during and after treatment with DAAs.

Changes in liver stiffness values assessed using transient elastography in chronic hepatitis B patients treated with tenofovir disoproxil fumarate: a prospective observational study

Background/AimsRegression of liver fibrosis during antiviral therapy in chronic hepatitis B (CHB) patients has been demonstrated, but data on the influence of long-term treatment with tenofovir disoproxil fumarate (TDF) on liver stiffness (LS) measured by transient elastography are scarce. We aimed to investigate the changes in LS values during the 144-week TDF therapy in treatment-naïve CHB patients.MethodsThis prospective observational study was conducted from April 2015 to July 2020 at CHA Bundang Medical Center. Laboratory tests and LS measurements were performed at baseline and repeated at weeks 12, 24, 48, 96, and 144. A significant decline in LS was defined as ≥ 30% decrease in LS value at week 96 from baseline.ResultsA total of 48 treatment-naïve CHB patients initiating TDF therapy were screened, and 36 patients were included in the final analysis (median age, 46 [interquartile range, 34.5–55.8] years; 19 men [52.8%]). During TDF therapy, the median LS values decreased from 13.8 kPa at baseline to 8.7 kPa, 6.5 kPa, and 6.4 kPa at weeks 48, 96, and 144, respectively (all P < 0.001). At week 96, virological and biochemical responses were achieved in 34 (94.4%) patients and 20 (76.9%) patients, respectively. Moreover, 21 of 36 (58.3%) patients showed a significant decline in LS value. A higher baseline LS value was a single independent predictor for the reduction in LS value at week 96 from baseline (P < 0.001).ConclusionsDuring the 144-week TDF therapy, LS values declined significantly in treatment-naïve CHB patients.

Non-organ-specific autoantibodies with unspecific patterns are a frequent para-infectious feature of chronic hepatitis D.

Infections with hepatotropic viruses are associated with various immune phenomena. Hepatitis D virus (HDV) causes the most severe form of viral hepatitis. However, few recent data are available on non-disease-specific and non-organ-specific antibody (NOSA) titers and immunoglobulin G (IgG) levels in chronic hepatitis D (CHD) patients. Here, we examined the NOSA titers and IgG levels of 40 patients with CHD and different disease courses and compared them to 70 patients with chronic hepatitis B (CHB) infection. 43% of CHD patients had previously undergone treatment with pegylated interferon-α (IFN-α). The antibody display of 46 untreated patients diagnosed with autoimmune hepatitis (AIH) was used as a reference. The frequency of elevated NOSA titers (CHD 69% vs. CHB 43%, p < 0.01), and the median IgG levels (CHD 16.9 g/L vs. CHB 12.7 g/L, p < 0.01) were significantly higher in CHD patients than in patients with CHB, and highest in patients with AIH (96%, 19.5 g/L). Also, the antinuclear antibody pattern was homogeneous in many patients with AIH and unspecific in patients with viral hepatitis. Additionally, f-actin autoantibodies were only detectable in patients with AIH (39% of SMA). In CHD patients, IgG levels correlated with higher HDV viral loads, transaminases, and liver stiffness values. IgG levels and NOSA were similar in CHD patients irrespective of a previous IFN-α treatment. In summary, autoantibodies with an unspecific pattern are frequently detected in CHD patients with unclear clinical relevance.

Artifacts in two-dimensional shear wave elastography of liver.

Artifacts are common when using two-dimensional shear wave elastography (2-D SWE) to measure liver stiffness (LS), but they are poorly recognized. To investigate the presence and influence of artifacts in 2-D SWE of liver. We included 158 patients with chronic liver disease, who underwent 2-D SWE examination by a novice and an expert. A cross line at the center of the elastogram was drawn and was divided it into four locations: top-left, top-right, bottom-left, and bottom-right. The occurrence frequency of artifacts in different locations was compared. The influence of artifacts on the LS measurements was evaluated by comparing the elastogram with the most artifacts (EMA) and the elastogram with the least artifacts (ELA). The percentage of elastograms with artifacts in the novice (51.7%) was significantly higher than that of the expert (19.6%) (P < 0.001). It was found that both operators had the highest frequency of artifacts at bottom-left, followed by top-left and bottom-right, and top-right had the lowest frequency. The LS values (LSVs) and standard deviation values of EMAs were significantly higher than those of ELAs for both operators. An intraclass correlation coefficient value of 0.96 was found in the LSVs of EMAs of the two operators, and it increased to 0.98 when the LSVs of the ELAs were used. Both operators had lower stability index values for EMAs than ELAs, but the difference was only statistically significant for the novice. Artifacts are common when using 2-D SWE to measure LS, especially for the novice. Artifacts may lead to the overestimation of LS and reduce the repeatability and reliability of LS measurements.

The Role of ElastPQ in Assessing Liver Stiffness for Non-Alcoholic Fatty Liver Disease in Patients Treated with Atypical Antipsychotic Drugs.

To evaluate the role of elastography point quantification (ElastPQ) for the quantitative assessment of stiffness in the fatty liver disease in mental disorder patients and to provide a noninvasive detection method for non-alcoholic fatty liver (NAFLD) caused by atypical antipsychotics drugs (AAPDs). A total number of 168 mental disorder patients treated with AAPDs and 58 healthy volunteers were enrolled in this study. All the subjects underwent ultrasound and ElastPQ tests. The basic data of the patients were analyzed. BMI, liver function, and the value of ElastPQ were considerably higher in the patient group than that in the healthy volunteers. The values of liver stiffness obtained by ElastPQ were increased gradually from 3.48(3.14-3.81) kPa in the normal liver to 8.15(6.44-9.88) in the severe fatty liver. The receiver operating characteristic (ROC) for the diagnosis of fatty liver with ElastPQ were 0.85, 0.79, 0.80, and 0.87 for the diagnosis of normal, mild, moderate, and severe steatosis, respectively, with a sensitive/specificity of 79%/76.4%, 85.7%/78.3%, 86.2%/73%, and 81.3%/82.1%, correspondingly. Moreover, ElastPQ in the olanzapine group was higher than those in the risperidone and aripiprazole groups (5.11(3.83-5.61) kPa vs 4.35(3.63-4.98) kPa, P < 0.05; 5.11(3.83-5.61) kPa vs 4.79(4.18-5.24) kPa, P < 0.05). After one-year treatment, the value of ElastPQ was 4.43(3.85-5.22) kPa, but it was 5.81(5.09-7.33) kPa in patients treated for more than three years. This value increased with treatment prolongation (P < 0.05). ElastPQ is a real-time, quantitative method for assessing the stiffness of NAFLD. The liver stiffness value could be varied in the different stages of fatty liver. Olanzapine has a considerable influence on liver stiffness. The long-term use of AAPDs can increase the stiffness value of fatty liver.

The Accuracy of Ultrasound Controlled Attenuation Parameter in Diagnosing Hepatic Fat Content.

The Controlled Attenuation Parameter (CAP score) is based on ultrasonic properties of retropropagated radiofrequency signals acquired by FibroscanTM (Echosens, Paris, France). Since ultrasound propagation is influenced by the presence of fat, CAP score was developed to quantify steatosis. The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy. A total of 150 patients underwent same-day liver biopsy and measurement of hepatic steatosis with Fibroscan. Only examinations with 10 satisfactory measurements, and an inter-quartile range of less than 30% of the median liver stiffness values were included for data analysis. Histological staging was then correlated with median values and Spearman correlation calculated. P values of <0.05 were considered statistically significant. For diagnosis of hepatic steatosis (HS), CAP could predict the steatosis S2 with AUROC 0.815 (95% CI 0.741-0.889), sensitivity (0.81) and specificity (0.73) when the optimal cut-off value was set at 288 dB/m. CAP detected histological grade S3 with AUROC 0.735 (95% CI 0.618-0.851), sensitivity (0.71) and specificity (0.74), with a cut-off value of 330 dB/m. The AUROC for steatosis grade S1 was 0.741 (95% CI 0.650-0.824), with a cut-off value of 263 dB/m with sensitivity 0.75 and specificity 0.70. Univariate analysis showed a correlation between CAP and diabetes (p 0.048). The performance of CAP to diagnose steatosis severity decreases as steatosis progresses. CAP is associated with diabetes but not other clinical factors and parameters of the metabolic syndrome.

Liver Involvement in Patients with Systemic Sclerosis: Role of Transient Elastography in the Assessment of Hepatic Fibrosis and Steatosis.

Background Systemic sclerosis (SSc) is a rare, multisystemic disorder of connective tissue characterized by widespread inflammation, vascular abnormalities, and both skin and visceral organ fibrosis. Tissue fibrosis is the final phase of a complex biological process of immune activation and vascular damage. Objectives The aim of the study was to assess hepatic fibrosis and steatosis in SSc patients by transient elastography (TE). Methods Fifty-nine SSc patients fulfilling the 2013 ACR/EULAR classification criteria were recruited. Clinical and laboratory findings, modified Rodnan skin score (mRSS), activity index, videocapillaroscopy, echocardiography, and lung function data were analyzed. Liver stiffness (LS) was measured by transient elastography (TE), with 7 kPa used as the cut-off value for significant liver fibrosis. In addition, hepatic steatosis was evaluated by means of controlled attenuation parameter (CAP) findings. Specifically, CAP values ≥ 238 ≤ 259 dB/m were considered consistent with mild steatosis (S1), values ≥ 260 ≤ 290 dB/m were compatible with moderate steatosis (S2), and values ≥ 291 dB/m were indicative of severe steatosis (S3). Results The median age of patients was 51 years, with a median disease duration of 6 years. The median LS was 4.5 (2.9-8.3) kPa; 69.5% of patients had no evidence of fibrosis (F0); 27.1% displayed LS values between 5.2 and 7 kPa; and only 3.4% of patients had LS values > 7 kPa (F3). The median CAP value for liver steatosis was 223 dB/m (IQR: 164-343). Overall, 66.1% of patients did not show evidence of steatosis (CAP values < 238 dB/m); 15.2% showed values consistent with mild (S1) steatosis (CAP value ≥ 238 ≤ 259 dB/m); 13.5% had moderate (S2) steatosis (CAP value ≥ 260 ≤ 290 dB/m); and 5.1% were deemed to have severe steatosis (S3) due to CAP values ≥ 291 dB/m. Conclusions Although systemic sclerosis is associated with fibrosis of the skin and several organs, only 3.4% of our patient population showed evidence of marked liver fibrosis, which is the same prevalence as that expected in the general population. Therefore, fibrosis of the liver did not appear to be a significant concern in SSc patients, albeit moderate fibrosis could still be detected in a significant proportion of subjects. A prolonged follow-up may clarify whether liver fibrosis in SSc patients may still progress. Likewise, the prevalence of significant steatosis was low (5.1%) and depended on the same variables associated with fatty liver disease in the general population. TE was shown to be an easy and valuable method for detection and screening of hepatic fibrosis in SSc patients with no additional risk factors for liver disease and may be useful to assess the potential progression of liver fibrosis over time.

Correlation between a New Point-Shear Wave Elastography Device (X+pSWE) with Liver Histology and 2D-SWE (SSI) for Liver Stiffness Quantification in Chronic Liver Disease.

The aim of this study was to investigate the feasibility, the correlation with previously validated 2D-SWE by supersonic imagine (SSI), and the accuracy in fibrosis-staging of a novel point shear-wave elastography device (X+pSWE) in patients with chronic liver disease. This prospective study included 253 patients with chronic liver diseases, without comorbidities potentially affecting liver stiffness. All patients underwent X+pSWE and 2D-SWE with SSI. Among them 122 patients also underwent liver biopsy and were classified according to histologic fibrosis. Agreement between the equipment was assessed with Pearson coefficient and Bland-Altman analysis, while receiver operator characteristic curve (ROC) analysis with Youden index was used to establish thresholds for fibrosis staging. A very good correlation was found between X+pSWE and 2D-SWE with SSI (r2 = 0.94; p < 0.001), with X+pSWE average liver stiffness values 0.24 kPa lower than those obtained with SSI. AUROC of X+pSWE for the staging of significant fibrosis (F2), severe fibrosis (F3) and cirrhosis (F4) using SSI as a reference standard was 0.96 (95% CI, 0.93-0.99), 0.98 (95% CI, 0.97-1) and 0.99 (95% CI, 0.98-1), respectively. The best cut-off values for diagnosing fibrosis ≥F2, ≥F3 and F4 were, respectively, 6.9, 8.5 and 12 for X+pSWE. According to histologic classification, X+pSWE correctly identified 93 out of 113 patients (82%) for F ≥ 2 and 101 out of 113 patients (89%) for F ≥ 3 using the aforementioned cut-off values. X+pSWE is a useful novel non-invasive technique for staging liver fibrosis in patients with chronic liver disease.

Comparison between Gradient-Echo and Spin-Echo EPI MR Elastography at 3 T in quantifying liver stiffness of patients with and without iron overload; a prospective study

ObjectivesTo compare the maximum axial area of the confidence mask and the calculated liver stiffness (LS) on gradient-echo (GRE) and spin-echo echo planar imaging (SE-EPI) MR elastography (MRE) in patients with and without iron deposition. Methods104 patients underwent MRE by GRE and SE-EPI sequences at 3 T. R2* values >88 Hz in the liver were categorized in the iron overload group. The maximum axial area and the corresponding LS values were measured by manually contouring the whole area on one slice with the largest confidence mask at both GRE and SE-EPI sequences. ResultsIn patients with iron overload, SE-EPI provided larger maximum axial confidence area in unfailed images (57.6 ± 41.7 cm2) compared to GRE (45.7 ± 29.1 cm2) (p-value = 0.007). In five patients with iron overload, imaging failed at GRE sequence, whereas at the SE-EPI sequence the maximum area of the confidence mask had a mean value of 33.5 ± 54.9 cm2. In livers without iron overload (R2*: 50.7 ± 13.1 Hz), the maximum area on the confidence mask was larger at SE-EPI (118.3 ± 41.2 cm2) than on GRE (105.1 ± 31.7 cm2) (P-value = 0.003). There was no significant difference in mean LS between SE-EPI (2.0 ± 0.3 kPa) and GRE (2.1 ± 0.5 kPa) in livers with iron overload (P value = 0.24). Similarly, in the group without iron overload, mean LS was 2.3 ± 0.7 kPa at SE-EPI and 2.4 ± 0.8 kPa at GRE sequences (P-value = 0.11). ConclusionsSE-EPI MRE can successfully provide similar LS measurements as GRE MRE. Furthermore, it provides a larger measurable area on the confidence mask in both groups with and without iron overload.

Comparison between Two-Dimensional and Point Shear Wave Elastography Techniques in Evaluating Liver Fibrosis Using Histological Staging as the Reference Standard: A Prospective Pilot Study.

Evaluation of hepatic fibrosis is essential to prevent liver-related morbidity and mortality. Although various types of ultrasound shear wave elastography (SWE) have been used and validated, there are limited studies on the relatively newer technique, two-dimensional SWE (2D-SWE). Therefore, this study aimed to compare the diagnostic performances of 2D-SWE and point SWE (p-SWE) for evaluating liver fibrosis using histology as the reference standard. To measure liver stiffness (LS) values, 87 patients underwent 2D-SWE and p-SWE using the same machine. Technical failures and unreliable measurements were also evaluated. The diagnostic performances of 2D-SWE and p-SWE were compared using area under the receiver operating characteristic (AUROC) curve analysis. No technical failures were observed in either method; however, unreliable measurements were less frequent in 2D-SWE (1/87 [1.1%]) than in p-SWE (8/87 [9.2%]) (p < 0.001). The AUROC of the LS values of 2D-SWE were significantly higher than those of p-SWE for diagnosing significant fibrosis (0.965 vs. 0.872, p = 0.022) and cirrhosis (0.994 vs. 0.886, p = 0.042). In conclusion, 2D-SWE is more reliable and accurate than p-SWE for diagnosing hepatic fibrosis.