Stiffness Measurement Research Articles

A comprehensive study of AFM stiffness measurements on inclined surfaces: theoretical, numerical, and experimental evaluation using a Hertz approach

Atomic Force Microscopy (AFM) is a leading nanoscale technique known for its significant advantages in the analysis of soft materials and biological samples. Traditional AFM data analysis is often based on the Hertz model, which assumes perpendicular indentation of a planar sample. However, this assumption is not always valid due to the varying geometries of soft materials, whether natural, synthetic or biological. In this study, we present a new theoretical model that incorporates correction coefficients into Hertz’s model to account for cone-like and spherical probes, and to consider local tilt at the probe-sample interface. We validate our model using finite element analysis (FEA) simulations and experimental AFM measurements on tilted polyacrylamide gels. Our results highlight the need to include local tilt at the probe-sample contact to ensure accurate AFM measurements. This represents a step forward in our understanding of the elastic properties at the surface of soft materials in the broadest sense.

Diagnostic accuracy of FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis in patients with chronic hepatitis B with metabolic dysfunction-associated fatty liver disease

Objective To evaluate the diagnostic value of the FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis (NASH) in patients with chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods All patients with CHB and MAFLD who underwent liver biopsy at the Zhenjiang Third Hospital affiliated with Jiangsu University between August 2010 and December 2022 were included in the analysis. The diagnostic accuracy of FAST, NFS, FibroScan, and FIB-4 for diagnosing NASH and liver fibrosis were evaluated based on the area under the receiver-operating characteristic curve (AUC). Results A total of 156 patients with CHB combined with MAFLD were included, including 69 with NASH and fibrosis stage 2 or higher (NASH+F ≥ 2), and 16 with NASH and cirrhosis (NASH+F4). The AUC of FAST, NFS, liver stiffness measurement (LSM), and FIB-4 for diagnosing NASH+F ≥ 2 was 0.739 (p < 0.001), 0.643 (p = 0.006), 0.754 (p < 0.001), and 0.665 (p = 0.003), respectively. The specificity of FAST, NFS, LSM, and FIB-4 was 67%, 51.8%, 78.6% and 76.8%, respectively, and the sensitivity was 75%, 78.6%, 67.9%, and 53.6%, respectively. No significant differences were found between groups. The AUC of FAST, NFS, LSM, and FIB-4 for diagnosing NASH+F4 was 0.650 (p = 0.038), 0.725 (p = 0.001), 0.851 (p < 0.001), and 0.560 (p = 0.533), respectively. The specificity of the FAST, NFS, LSM, and FIB-4 was 55.9%, 50.0%, 71.6%, and 75.5%, respectively and the sensitivity was 80.0%, 100%, 100%, and 50.0%, respectively. The differences between AUCs of FIB-4 and FAST compared with LSM were 0.291 and 0.201, respectively (p < 0.05). Conclusion In patients with CHB combined with MAFLD, FAST did not have better accuracy than NFS and FIB-4 for predicting fibrotic NASH, whereas LSM had better accuracy than FAST and FIB-4.

Estimating reference intervals from an IPD meta-analysis using quantile regression

BackgroundReference intervals, which define an interval in which a specific proportion of measurements from a healthy population are expected to fall, are commonly used in medical practice. Synthesizing information from multiple studies through meta-analysis can provide a more precise and representative reference interval than one derived from a single study. However, the current approaches for estimating the reference interval from a meta-analysis mainly rely on aggregate data and require parametric distributional assumptions that cannot always be checked.MethodsWith the availability of individual participant data (IPD), non-parametric methods can be used to estimate reference intervals without any distributional assumptions. Furthermore, patient-level covariates can be introduced to estimate personalized reference intervals that may be more applicable to specific patients. This paper introduces quantile regression as a method to estimate the reference interval from an IPD meta-analysis under the fixed effects model.ResultsWe compared several non-parametric bootstrap methods through simulation studies to account for within-study correlation. Under fixed effects model, we recommend keeping the studies fixed and only randomly sampling subjects with replacement within each study. ConclusionWe proposed to use the quantile regression in the IPD meta-analysis to estimate the reference interval. Based on the simulation results, we identify an optimal bootstrap strategy for estimating the uncertainty of the estimated reference interval. An example of liver stiffness measurements, a clinically important diagnostic test without explicitly established reference range in children, is provided to demonstrate the use of quantile regression in estimating both overall and subject-specific reference intervals.

Hepatic steatosis estimated by VCTE-derived CAP scores was associated with lower risks of liver-related events and all-cause mortality in patients with chronic liver disease.

The Controlled Attenuated Parameter (CAP) score derived from vibration-controlled transient elastography (VCTE, i.e. Fibroscan®) is a well-validated marker of hepatic steatosis. It is unclear if CAP scores are associated with risks of liver-related outcomes or all-cause mortality. In this retrospective cohort study, we identified 7,587 U.S. Veterans (2,689 with cured hepatitis C [HCV], 1,523 with alcohol-associated liver disease [ALD], 3,375 with metabolic dysfunction-associated steatotic liver disease [MASLD]) who underwent VCTE between 5/2015-12/2021. We followed patients for new hepatic decompensation, hepatocellular carcinoma (HCC), and death from the VCTE date until 1/1/2022. Multivariable Cox-proportional hazards regression was used to assess for the associations between CAP measurements and clinical outcomes, adjusting for age, sex, race/ethnicity, body mass index, Charlson Comorbidity Index, diabetes, liver disease etiology, liver stiffness measurements, and FIB-4, and was reported separately by disease etiology and advanced fibrosis status. Over a median follow-up time of ∼1.9 years, hepatic steatosis (grades 1-3 vs. 0) was associated with a lower risk of death (aHR 0.70, 95% CI: 0.57-0.85). Among patients with MASLD, hepatic steatosis was associated with a lower risk of decompensation (aHR 0.54, 95% CI: 0.32-0.90) and death (aHR 0.52, 95% CI: 0.37-0.73). These associations persisted in subgroup analyses of patients with advanced fibrosis and without cirrhosis. Among patients who underwent VCTE in clinical practice, the presence of substantial hepatic steatosis estimated by the CAP score was associated with lower all-cause mortality among all patients and lower risk of decompensation and death among those with MASLD.

Machine Learning Models for Predicting Significant Liver Fibrosis in Patients with Severe Obesity and Nonalcoholic Fatty Liver Disease.

Although noninvasive tests can be used to predict liver fibrosis, their accuracy is limited for patients with severe obesity and nonalcoholic fatty liver disease (NAFLD). We developed machine learning (ML) models to predict significant liver fibrosis in patients with severe obesity through noninvasive tests. This prospective study included 194 patients with severe obesity who underwent wedge liver biopsy and metabolic bariatric surgery at Taipei Medical University Hospital between September 2016 and December 2020. Significant liver fibrosis was defined as a fibrosis score ≥ 2. Patients were randomly divided into a training group (70%) and a validation group (30%). ML models, including support vector machine, random forest, k-nearest neighbor, XGBoost, and logistic regression, were trained to predict significant liver fibrosis, using DM status, AST, ALT, ultrasonographic fibrosis scores, and liver stiffness measurements (LSM). An ensemble model including these ML models was also used for prediction. Among the ML models, the XGBoost model exhibited the highest AUROC of 0.77, with a sensitivity, specificity, and accuracy of 61.5%, 75.8%, and 69.5%, in validation set, while LSM, AST, ALT showed strongest effects on the model. The ensemble model outperformed all ML models in terms of sensitivity, specificity, and accuracy of 73.1%, 90.9%, and 83.1%. For patients with severe obesity and NAFLD, the XGBoost model and the ensemble model exhibit high predictive performance for significant liver fibrosis. These models may be used to screen for significant liver fibrosis in this patient group and monitor treatment response after metabolic bariatric surgery.

20-HETE, Blood Pressure, and Vascular Stiffness in Young Adults.

Cytochrome-P450 eicosanoids from arachidonic acid, including vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-HETE, are important in regulating blood pressure, vascular tone, and cardiac and renal function. This study examined plasma 20-HETE and EETs in relation to blood pressure and vascular stiffness in a cohort of 1054 community-dwelling young adults from the Raine Study at 27 years. Plasma 20-HETE, EETs, and their hydroxylated products were measured by liquid chromatography-tandem mass spectrometry. Pulse wave velocity and aortic distensibility were measured to assess vascular stiffness. Sex differences were assessed using univariate analysis. Multiple regression models assessed the relationship between 20-HETE and systolic blood pressure (SBP) and measures of vascular stiffness. The regression model for SBP showed a positive relationship with plasma 20-HETE (β, 0.092; P<0.0001), after adjusting for sex (P<0.0001), body mass index (P<0.0001), (ln)triglycerides (P<0.0001), and (ln)HOMA-IR (P=0.015), and accounted for 29% of the variance in SBP. 20-HETE was positively related to pulse wave velocity (β, 0.059; P=0.021); after adjusting for sex (P<0.0001), SBP (P<0.0001), (ln)triglycerides (P=0.014), (ln)HOMA-IR (P=0.0001), (ln)high-sensitivity C-reactive protein (P=0.005), and age (P=0.002), the model accounted for 34% of the variance in pulse wave velocity. 20-HETE was inversely associated with aortic distensibility (β, -0.051; P=0.029), independent of sex (P<0.0001), SBP (P<0.0001), and (ln)HOMA-IR (P<0.0001); the model accounted for 25% of the variance in aortic distensibility. Plasma EETs were not significant predictors of SBP or vascular stiffness. In young adults, 20-HETE may play a fundamental role in regulating blood pressure and vascular stiffness independent of numerous cardiometabolic risk factors and cytochrome 450-derived EETs. URL: https://www.anzctr.org.au; Unique identifier: CTRN12617001599369.

Longitudinal evaluation of pediatric and young adult metabolic dysfunction-associated steatotic liver disease defined by MR elastography.

To inform clinical monitoring of children and young adults with metabolic dysfunction-associated steatotic liver disease (MASLD) by characterizing the real-world natural history of MASLD and identifying baseline predictors of liver disease progression. This retrospective study included consecutive patients ages < 23 years with MASLD who underwent serial MR elastography (MRE) and/or MR fat fraction (FF) examinations between 09/2009 and 11/2022. Outcomes of MASLD were defined based on maximum ratio values. A relative change ≥ 19% in liver stiffness measures (LSM) and an absolute change ≥ 5% for liver FF were considered clinically meaningful. Random intercept models characterized the yearly rate of change in LSM (kilopascals per year) and FF (percentage per year). One hundred twenty-one patients (87 males, mean age at baseline: 12 ± 3 [SD] years) underwent 297 MRE examinations. The mean interval between the first and last MRE was 34 (± 24) months (range: 1-120 months). Among the 114 patients with serial LSM, 33% (38/114) showed progression, 46% (53/114) remained stable, and 21% (23/114) showed regression. Among the 88 patients with serial FF measures, 57% (50/88) showed progression, 2% (2/88) remained stable, and 41% (36/88) showed regression. LSM progression was associated with Hispanic ethnicity, baseline BMI-for-age percentile, baseline mean liver FF, and GGT changes over time. Predictors for liver FF progression included ALT, AST, GGT, and LDL. In a real-world sample of children and young adults with MASLD who underwent serial liver MRI, a minority of patients demonstrated improvements in liver stiffness or FF over time. Question In children, there is scarce data regarding the natural history of MASLD. Findings In this retrospective study, most children and young adults with MASLD had either unchanged or worsening liver stiffness (n = 91/114, 79%) and liver fat (n = 52/88, 59%). Clinical relevance Our findings emphasize the need for optimized care in pediatric MASLD. The identified risk factors for the progression of liver fat and stiffness may help to identify children who require interventions beyond changes in lifestyle.

Body mass index of 23 or greater is relevant to hepatic steatosis and fibrosis in patients with harmful alcohol use.

Steatotic liver disease, characterized by a combination of metabolic dysfunction, alcohol use, or specific etiologies, is a leading cause of chronic liver disease. However, the role of metabolic dysfunction in chronic liver disease with harmful alcohol use remains unclear. This study aimed to investigate factors associated with hepatic steatosis and fibrosis in patients with harmful alcohol use. Over a 2-year period, we registered patients with harmful alcohol use, defined by an Alcohol Use Disorders Identification Test score of 8 or higher. We retrospectively analyzed background information, blood test results, ultrasound-guided attenuation parameter (attenuation coefficient), and liver stiffness measurement. Hepatic steatosis was defined as attenuation coefficient ≥0.65dB/cm/MHz, and fibrosis as liver stiffness measurement ≥7.5kPa. The study included 131 patients (82% men, median age 59years). Linear regression analysis revealed significant associations with attenuation coefficient for body mass index ≥23 (0.08, p<0.0001) and age (-0.002, p=0.002). Liver stiffness measurement was associated with body mass index ≥23 (2.52, p=0.001), aspartate aminotransferase (0.02, p=0.0189), gamma-glutamyl transpeptidase (0.008, p<0.0001), platelet count (-0.02, p=0.001), and prothrombin international normalized ratio (26.40, p<0.0001). Among the four groups classified by the presence or absence of steatosis and fibrosis, patients with fibrosis, but without steatosis, demonstrated the lowest liver reserve. In contrast, patients with both steatosis and fibrosis showed higher aspartate aminotransferase and gamma-glutamyl transpeptidase levels. Body mass index is associated with both hepatic steatosis and fibrosis in patients with harmful alcohol use.

Hepatocellular Cancer Surveillance in Patients with Advanced Chronic Liver Disease

BackgroundPatients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD.MethodsFrom 3016 patients with ACLD screened in 17 European and Chinese centers, 2340 patients with liver stiffness measurement (LSM) determined using different techniques (two-dimensional shear-wave elastography [2D-SWE], transient elastography, and point shear-wave elastography) and with different disease severities were included. Cox regression was used to explore risk factors for HCC. We used these data to create an algorithm, named PLEASE, but referred to in this manuscript as “the algorithm”; the algorithm was validated in internal and two external cohorts across elastography techniques.ResultsHCC developed in 127 (5.4%) patients during follow-up. LSM by 2D-SWE (hazard ratio: 2.28) was found to be associated with developing HCC, alongside age, sex, etiology, and platelet count (C-index: 0.8428). We thus established the algorithm with applicable cutoffs, assigning a maximum of six points: platelet count less than 150×109/l, LSM greater than or equal to 15 kPa, age greater than or equal to 50 years, male sex, controlled/uncontrolled viral hepatitis, or presence of steatotic liver diseases. Within 2 years, with a median follow-up of 13.7 months, patients in the high-risk group (≥4 points) had an HCC incidence of 15.6% (95% confidence interval [CI], 12.1% to 18.7%) compared with the low-risk group, at 1.7% (95% CI, 0.9% to 2.5%).ConclusionsOur algorithm stratified patients into two groups: those at higher risk of developing HCC and those at lower risk. Our data provide equipoise to test the prospective utility of the algorithm with respect to clinical decisions about screening patients with ACLD for incident HCC. (Funded by the German Research Foundation and others; ClinicalTrials.gov number, NCT03389152.)

Current strategies for predicting post-hepatectomy liver failure and a new ultrasound-based nomogram

Liver cancer is associated with a few factors, such as viruses and alcohol consumption, and hepatectomy is an important treatment for patients with liver cancer. However, post-hepatectomy liver failure (PHLF) is the most serious complication and has a high mortality rate. Effective prediction of PHLF allows for the adjustment of clinical treatment strategies and is critical to the long-term prognosis of patients. Many factors have been associated with the development of PHLF, so there is an increasing interest in the development of predictive models for PHLF, such as nomograms that integrate intra-operative factors, imaging and biochemical characteristics of the patient. Ultrasound, as a simple and important examination method, plays an important role in predicting PHLF, especially the Nomogram established based on ultrasound measurements of liver stiffness and spleen area provides a more convenient way to predict the occurrence of PHLF.

Association between Body Fat Distribution and Nonalcoholic Fatty Liver Disease/Fibrosis Based on Race/Ethnicity.

Body fat distribution may impact nonalcoholic fatty liver disease (NAFLD) and significant fibrosis differently according to race/ethnicity. We determined the relationship between body fat distribution and NAFLD/significant fibrosis according to race/ethnicity. A cross-sectional study of 2,395 participants used the National Health and Nutrition Examination Survey 2017 to 2018. NAFLD and significant fibrosis (≥F2) were defined by controlled attenuation parameter scores and liver stiffness measurements on transient elastography, respectively. Visceral and subcutaneous fat volumes were defined by dual-energy X-ray absorptiometry. The odds ratio (OR) for NAFLD per 1-standard deviation in visceral fat volume and subcutaneous fat volume was 2.31 (95% confidence interval [CI], 1.50 to 3.39) and 1.93 (95% CI, 1.43 to 2.61) in total population, respectively. Visceral fat in non-Hispanic Blacks had the highest odds for NAFLD (OR, 2.86; 95% CI, 1.45 to 5.62), and non-Hispanic Whites (OR, 2.29; 95% CI, 1.19 to 4.40) and non-Hispanic Asians (OR, 1.61; 95% CI, 1.13 to 2.29) were in order. Significant associations between subcutaneous fat volume (OR, 2.10; 95% CI, 1.34 to 3.29; P=0.003) or visceral fat volume (OR, 1.35; 95% CI, 1.05 to 1.73; P=0.023) and significant fibrosis were noted among individuals with NAFLD. Hispanics had the highest odds for NAFLD-associated significant fibrosis (OR, 2.74; 95% CI, 1.32 to 5.70), and non-Hispanic Whites (OR, 2.35; 95% CI, 1.11 to 4.98) and non-Hispanic Asians (OR, 2.01; 95% CI, 1.01 to 4.01) were in order. Visceral adiposity was associated with NAFLD and significant fibrosis despite the association of subcutaneous adiposity in NAFLD and significant fibrosis. Racial/ethnic differences in the association between body fat distribution on NAFLD and significant fibrosis were noted.

Association between changes in body composition and progression of liver fibrosis in patients with type 2 diabetes mellitus.

The correlation between type 2 diabetes mellitus (T2DM) and the occurrence of liver fibrosis is well-established. However, the longitudinal association between body composition and liver fibrosis progression in patients with T2DM remains incompletely explored. Total of 390 patients with T2DM underwent body composition assessments, followed by a median duration of 2.13 years. The calculated parameters included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F) and appendicular skeletal muscle mass/trunk fat mass ratio (A/T). Liver fibrosis was evaluated through liver stiffness measurement (LSM). Patients were classified according to BMI and body composition, followed by a comprehensive investigation into the impact of body composition changes on liver fibrosis outcomes. Among 72 patients with incident advanced liver fibrosis at readmission, ΔBMI, ΔFMI and ΔTFMI increased, while ΔM/F and ΔA/T decreased. Individuals who kept obese had a dramatically elevated hazard of incident advanced liver fibrosis compared to those who kept non-obese, with an adjusted odds ratio of 3.464. When TFMI heightened, the hazard of incident advanced liver fibrosis was 3.601 times higher compared to the decreased group. Additionally, individuals in increased ASMI and A/T groups showed a slight advantage in preventing incident advanced liver fibrosis compared to the stable groups. Stable obesity was associated with a greater hazard of liver fibrosis advancement, and an increase in TFMI may promote the progression of liver fibrosis. Maintaining a balanced muscle/fat ratio appeared to help prevent the progression.

A 3D fast MR elastography sequence with interleaved multislab acquisition and Hadamard encoding.

To enhance the functional capability of MRI, this study aims to develop a novel MR elastography (MRE) sequence that achieves rapid acquisition without distortion artifacts. A displacement-encoded stimulated echo (DENSE) with multiphase acquisition scheme was used to capture wave images. A center-out golden-angle stack-of-stars sampling pattern was introduced for improved SNR and data incoherence. A combination of Hadamard encoding and interleaved multislab acquisition schemes was used to increase the acquisition efficiency of MRE data with multiple directions and phase offsets. A generalized parallel-imaging and compressed-sensing method was further applied to accelerate the acquisition process. The imaging results of the proposed sequence were compared with those from six gradient echo (GRE)/EPI/DENSE-based MRE sequences via phantom and brain acquisitions. The proposed sequence achieved a 6-fold acceleration compared with GRE MRE. With the application of a conventional parallel-imaging and compressed-sensing algorithm, the scanning speed was further accelerated by 8-fold, matching the speed of EPI-based MRE. Phantom tests revealed small variances in stiffness measurements across the seven sequences (< 9.23%). The proposed sequence exhibited a higher contrast-to-noise ratio (1.38) than the two EPI-based sequences (0.61/0.76) and similar to GRE-based sequences (1.34/1.22/1.58). Brain imaging validated the effectiveness of the proposed sequence in accurate stiffness estimation and distortion artifact avoidance. A rapid DENSE-based MRE sequence with interleaved multislab acquisition and Hadamard encoding was developed at a speed matching EPI-based sequences, without compromising SNR or introducing distortion artifacts.

Nanomechanical thermometry for probing sub-nW thermal transport

Accurate local temperature measurement at micro and nanoscales requires thermometry with high resolution because of ultra-low thermal transport. Among the various methods for measuring temperature, optical techniques have shown the most precise temperature detection, with resolutions reaching (~10−9 K). In this work, we present a nanomechanical device with nano-Kelvin resolution (~10−9 K) at room temperature and 1 atm. The device uses a 20 nm thick silicon nitride (SiN) membrane, forming an air chamber as the sensing area. The presented device has a temperature sensing area >1 mm2 for micro/nanoscale objects with reduced target placement constraints as the target can be placed anywhere on the >1 mm2 sensing area. The temperature resolution of the SiN membrane device is determined by deflection at the center of the membrane. The temperature resolution is inversely proportional to the membrane’s stiffness, as detailed through analysis and measurements of stiffness and noise equivalent temperature (NET) in the pre-stressed SiN membrane. The achievable heat flow resolution of the membrane device is 100 pW, making it suitable for examining thermal transport on micro and nanoscales.

Diagnostic insights into splenic pathologies: the role of multiparametric ultrasound.

Ultrasound(US) evaluation of the spleen is mandatory in the assessment of patients with chronic liver disease, and splenomegaly can be a sign of systemic diseases. However, due to the lack of distinctive ultrasound findings in specific splenic pathologies, clinical diagnosis can be very challenging. Splenomegaly, defined by increased splenic dimensions, can indicate underlying systemic conditions and is a common manifestation of portal hypertension (PH). Ultrasound and Doppler techniques help assessing splenic involvement in PH. Splenic stiffness measurement, using elastography, offers additional diagnostic accuracy, especially when liver stiffness measurements are inconclusive. CEUS enhances the diagnostic capability for focal splenic lesions, differentiating between benign and malignant lesions by their distinct enhancement patterns, and plays also a critical role in the context of splenic traumatic pathology. Overall, CEUS significantly improves the characterization of splenic pathology, reducing the need for invasive procedures and ensuring appropriate patient management. This review article describes the normal US findings of the spleen and examines the role of multiparametric US in the evaluation of the most common splenic pathologies encountered in the daily clinical practice.

MASLD in persons with HIV is associated with high cardiometabolic risk as evidenced by altered advanced lipoprotein profiles and targeted metabolomics

BackgroundMetabolic dysfunction associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk in persons with HIV (PWH). The lipidomic and metabolomic alterations contributing to this risk are poorly understood. We aimed to characterize the advanced lipoprotein and targeted metabolomic profiles in PWH and assess if the presence and severity of MASLD influence these profiles.MethodsThis is a cross-sectional analysis of a prospectively enrolled multicenter cohort. PWH without alcohol abuse or known liver disease underwent vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Lipidomic and metabolomic profiling was undertaken with nuclear magnetic resonance (NMR) spectroscopy. Hepatic steatosis was defined as CAP ≥ 263 dB/m and clinically significant fibrosis (CSF) as LSM ≥ 8 kPa. Logistic regression models assessed associations between MASLD, CSF and lipidomic and metabolic parameters.ResultsOf 190 participants (71% cisgender male, 96% on antiretroviral therapy), 58% had MASLD and 12% CSF. Mean (SD) age was 48.9 (12.1) years and body mass index (BMI) 29.9 (6.4) kg/m2. Compared to PWH without MASLD (controls), PWH with MASLD had lower HDL-C but higher total triglyceride, VLDL-C, branched-chain amino acids, GlycA, trimethylamine N-oxide levels, Lipoprotein-Insulin Resistance and Diabetes Risk Indices. There were no significant differences in these parameters between participants with MASLD with or without CSF. In a multivariable regression analysis, MASLD was independently associated with changes in most of these parameters after adjustment for age, gender, race/ethnicity, type 2 diabetes mellitus, BMI, and lipid lowering medications use.ConclusionsMASLD in PWH is independently associated with altered advanced lipoprotein and targeted metabolic profiles, indicating a higher CVD risk in this population.

Erratum: Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

Erratum: Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

A multi-institutional study on Ultrasound image analysis for staging HBV-derived liver fibrosis: a potential non-invasive alternative to liver stiffness measurement

Background: Liver stiffness measurement is principal for staging liver fibrosis but not included in routine examinations. We investigated whether comparable diagnostic performance can be achieved by mining ultrasound images and developing a novel serum index (NSI). Methods: Texture features were extracted from ultrasound images. Spearman correlation and logistics regression selected independent variables for significant (F≥2) and advanced (F≥3) fibrosis. We compared the diagnostic performance of transient elastography (TE), ultrasound image biomarker (UIB), conventional serum indices (APRI, FIB-4, GPR), and NSI in 365 chronic hepatitis B patients. Results: Among patients, 52.1% had significant fibrosis and 24.2% had advanced fibrosis. PLT, GGT, prealbumin, and globulin were incorporated into NSI. In the validation group, TE achieved the best performance (AUC: 0.765 [0.690-0.849] for significant fibrosis; 0.812 [0.745-0.878] for advanced fibrosis), followed by UIB (AUC: 0.712 [0.629-0.795]; 0.678 [0.595-0.763]) and NSI (AUC: 0.630 [0.534-0.725]; 0.659 [0.572-0.745]), outperforming conventional indices. Conclusions: Texture analysis enhances ultrasound's diagnostic utility, but TE remains superior. When TE is unavailable, ultrasound image analysis and NSI, incorporating prealbumin, can serve as alternative tools for fibrosis staging.

LiMAx test and ultrasound elastography to measure biomarkers of declining liver function in patients with liver fibrosis: A correlation analysis.

Monitoring liver changes is crucial in the management of liver fibrosis. Current diagnostic methods include liver function tests such as the Liver Maximum Capacity (LiMAx) test and measurements of liver stiffness. While the LiMAx test quantifies liver function through 13C-methacetin metabolism, ultrasound (US) elastography noninvasively assesses liver stiffness. The relationship between the findings of these methods in patients with liver fibrosis is not fullyunderstood. This study evaluated the correlation between LiMAx measurements of liver function and US elastography-based liver stiffness measurements to better understand the interplay between functional and structural liver parameters in fibrotic liver disease. Additionally, the relationship between body mass index (BMI) and these parameters isevaluated. This retrospective study analysed data from 97 patients who underwent both LiMAx testing and real-time elastography, resulting in a total data set of 108 examinations. The correlations between the results of the LiMAx test and elastography and their relationships with body mass index (BMI) were analysed. There was a significant negative correlation (r = -0.25, p < 0.05) between LiMAx test values and liver stiffness measurements. BMI was significantly negatively correlated with LiMAx values (r = -0.29, p < 0.001) but not significantly correlated with liver stiffness values. This retrospective study confirms the results of previous studies showing a notable but weak association between liver function and liver stiffness. Our results highlight the potential value of both tests as complementary tools for the evaluation of liver health, reinforcing the necessity for a multimodal approach to liver assessment.

Arterial stiffness measured by pulse wave velocity correlated with cognitive decline in hypertensive individuals: a systematic review

BackgroundArterial stiffness is a degenerative modification in the arterial wall that significantly affects normal aging. Arterial hypertension is a major risk factor for cerebrovascular impairment. Pulse wave velocity (PWV) is an established gold standard for measuring arterial stiffness. Studies demonstrated that individuals with elevated blood pressure (BP) and PWV are more likely to experience worse cognitive decline compared to those with either condition alone. The aim of this review is to explore the clinical importance of arterial stiffness for cognitive function in older adults with hypertension.MethodsThe systematic review was reported following the PRISMA 2020 guidelines and Cochrane protocol and was registered in NIHR PROSPERO. PubMed, Embase, Web of Science, CINAHL, and Cochrane databases were searched for relevant publications up to December 2022. Articles were filtered by age and type of study and only those including a sample size of at least 500 individuals were selected. Screening of abstracts and full-text review of selected articles were carried out through Covidence.ResultsThe full-text review included a total of 434 articles. Twenty-eight prospective studies have met the inclusion criteria. Selected studies used PWV as the main measurement of stiffness: 24 used carotid-femoral, 2 used brachial-ankle, 1 used aortic PWV, and 11 compared different measures. Studies demonstrated a strong association between increased BP and PWV with brain damage and cognitive deterioration among older adults. One study did not find an interaction with hypertension, while another study found that PWV but not BP was associated with cognitive decline. Few studies showed that the association between stiffness and cognitive outcomes was not significant after adjustment for BP. Several authors suggested that cognitive decline induced by stiff vasculature and hypertension benefited from antihypertensive therapy.ConclusionThe results of this review demonstrated that arterial hypertension is an important factor linking arterial stiffness to cognitive health in older individuals. BP plays a crucial role in brain integrity, whereas PWV was shown to be a strong measure associated with cognitive decline. Together, they can lead to disabling cognitive outcomes. Early screening of stiffness, BP control, and compliance with treatment are essential for cerebrovascular disease prevention.Trial registrationNIHR PROSPERO registry ID: CRD42022379887.