Assessment Of Liver Steatosis Research Articles

Quantitative ultrasound techniques and biochemical markers to assess liver steatosis and fibrosis in newly diagnosed acromegaly.

The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. The aim of this study was to use quantitative ultrasound techniques and biochemical markers to assess liver steatosis and liver fibrosis in newly diagnosed acromegaly. This single-center, cross-sectional study included 23 patients with newly diagnosed acromegaly and 46 age, sex, body mass index (BMI) and waist circumference (WC)-matched controls. Liver steatosis was assessed using tissue attenuation imaging (TAI), and stiffness, indicative of fibrosis, was assessed by shear wave elastography (SWE). Serum IGFBP7 and CK18 were studied by ELISA. The acromegaly group had significantly lower liver steatosis (p = 0.006) and higher liver stiffness (p = 0.004), serum IGFBP7 (p = 0.048) and CK18 (p = 0.005) levels than the control group. The presence of fibrosis (p = 0.012) was significantly higher in the acromegaly group than in the control group. Moreover, CK18 was positively correlated with liver stiffness, WC, HOMA-IR, HbA1c, and triglyceride. In the acromegaly group, liver steatosis was negatively correlated with GH level. Stepwise multiple linear regression analysis revealed that BMI (p = 0.008) and CK18 (p = 0.015) were independent risk factors for increased liver stiffness. This study showed that there was an increased presence of liver fibrosis independent of liver steatosis in newly diagnosed acromegaly. Serum CK18 appears to be a potential marker of increased liver fibrosis in acromegaly.

Recent advances in noninvasive assessment of liver steatosis.

Due to the steatosis epidemic, noninvasive quantification of liver fat content is of great interest. Magnetic resonance (MR) techniques, including proton MR spectroscopy (MRS) and MR chemical shift imaging can quantify liver fat by measuring, directly or indirectly (the latter), the proton density fat fraction (PDFF). They have shown excellent diagnostic accuracy and are currently the reference standard for the noninvasive assessment of liver steatosis and are used in clinical trials for evaluating the change in liver fat over time. Using ultrasound (US), three different quantitative parameters can be obtained to estimate liver fat: attenuation coefficient, backscatter coefficient, and speed of sound. Controlled attenuation parameter (CAP), which estimates the attenuation of the US beam, was the first algorithm available and is performed with a non-imaging system. Currently, several other algorithms are available on B-mode imaging ultrasound systems, and they have shown an accuracy similar to or higher than the CAP. This article reports the current knowledge about their application in patients with metabolic dysfunction-associated steatotic liver disease.

Optimizing the number of valid measurements for the attenuation coefficient to assess hepatic steatosis in MAFLD patients: A study of 139 patients who underwent liver biopsy

Abstract Purpose We investigated the optimal number of valid measurements (VMs) for the attenuation coefficient (AC) to assess liver steatosis using attenuation imaging (ATI) and explored factors that may affect AC measurement in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Materials and Methods A total of 139 patients with MAFLD who underwent ATI and liver biopsy were enrolled. Hepatic steatosis was graded as S0–3 according to the SAF scoring system. The AC values from 1, 2, 3, 5, and 7 VMs were compared with the degree of liver steatosis. The correlation between AC values from different VMs was analyzed. The diagnostic performance of AC from different VMs at each steatosis grade was compared. The factors related to AC were identified using linear regression analysis. Results The mean AC values from 1, 2, 3, 5, and 7 VMs were not significantly different between grades S0–3 (p=n.s. for all). Bland-Altman analysis showed the mean difference in AC values of 3 VMs and 7 VMs was 0.003 dB/cm/MHz, which was smaller compared with 2 VMs, and close to 5 VMs. The intraclass correlation coefficients of AC were all > 0.90 among different VM groups. AC values from different VMs all significantly predicted steatosis grade ≥S1, ≥S2, and S3 without significant statistical differences (p=n.s. for all). The multivariate analysis showed that the hepatic steatosis grade and triglyceride level were factors independently associated with AC. Conclusion Three valid measurements of AC may be adequate to ensure the accuracy and reproducibility of hepatic steatosis assessment. The degree of liver steatosis and the triglyceride level significantly affected AC values.

Assessment of hepatic steatosis of potential living donor before liver transplantation using liver/spleen CT attenuation ratio compared to liver biopsy

BackgroundHepatic steatosis has become a major worldwide health problem, so assessment of hepatic steatosis in potential living donors is crucial prior to liver transplantation. Until now liver biopsy (LB) is considered the gold standard for diagnosing steatosis before transplantation, however steatosis assessment using imaging modalities, such as computerized tomography (CT), would be better for the donor, due its non-invasiveness. This study aimed to assess the efficacy of CT as a semiquantitaive tool for liver steatosis assessment in liver donors in comparison to liver biopsy results.MethodsThis cross-sectional study was carried out on 53 potential liver graft donors. All patients were subjected to non-contrast CT of the abdomen, tru-cut liver biopsy, and histopathological evaluation. The CT liver attenuation (CTL), the hepatic/splenic CT attenuation ratio (CTL/S) and difference between hepatic attenuation value and splenic attenuation values (CTL–S) were determined as well as the correlations of these indices and the findings of Liver biopsy (LB) were compared.ResultsAccording to the hepatosteatosis grades in the pathology results, the patients were divided into two groups: group A: 38 patients with grade 0 hepatosteatosis and group B: 15 patients with grade 1 and 2 hepatosteatosis. CTL, CTL–S, CTL/S, ratio of mean right hepatic lobe and splenic attenuation (RT/S) and ratio of mean left hepatic lobe and splenic attenuation (LT/S) were found to be effective in the diagnosis of hepatosteatosis grades at cutoff values ≤ 55.4, ≤ 8.7, ≤ 1.17, ≤ 1.1548 and ≤ 1.2971 with 80%, 80%, 73.3%, 86.7% and 86.7% sensitivity and 71.1%, 56.8%, 73.7% 71.1% and 50.0% specificity respectively. Also, CTL/S was found to be very effective in the diagnosis of grade II hepatosteatosis at cutoff values ≤ 0.9 with 100% sensitivity and 100% specificity. There was significant negative correlations between the CT indexes and degree of hepatosteatosis.ConclusionsCompared to biopsy results, CT noninvasive indices strongly predicted the presence of hepatosteatosis, which can help in avoiding the necessity for this invasive technique.

Reproducibility and accuracy of a pocket-size ultrasound device in assessing liver steatosis

BackgroundThis diagnostic prospective study compared the feasibility and diagnostic accuracy of Pocket-size Ultrasound Devices (PUDs) against standard ultrasound (US) in detecting liver steatosis using the controlled attenuation parameter (CAP) and liver biopsy as reference standards. Materials and MethodsConsecutive patients with chronic liver diseases were assessed for the presence of steatosis using PUD and US. A CAP cut-off value >275 dB/m was applied to establish ≥S1. A 26-patient subgroup underwent liver biopsy. PUD reproducibility was evaluated using Cohen's k statistic. Diagnostic accuracy of PUD and US was given as Sensibility (Sn), Specificity (Sp), Positive and Negative Predictive Values (PPV, NPV), positive and negative Likelihood Ratio (LR+, LR-). Results81 consecutive patients (69% males) with multiple etiologies were enroled. PUD inter-observer agreement was good (k 0.77, 95%CI 0.62–0.93). PUD and US identified ≥S1 according to CAP values respectively with Sn 0.87, Sp 0.61, PPV 0.49, NPV 0.91, LR+ 2.04, LR- 0.07, AUROC 0.74 and Sn 0.96, Sp 0.54, PPV 0.47, NPV 0.97, LR+ 2.10, LR- 0.07, AUROC 0.75. ConclusionsPUD shows good reproducibility and diagnostic accuracy in ruling liver steatosis out, representing a useful point-of-care tool to avail of hepatologists interested in excluding NAFLD, but with basic US skills.

Association of fat-to-muscle ratio with non-alcoholic fatty liver disease: a single-centre retrospective study

ObjectivesSarcopenia is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Studies evaluating the association between the fat-to-muscle ratio (FMR) and NAFLD are limited. Therefore, the aim of our...

Modern ultrasonic methods of diagnostics of hepatic steatosis

The prevalence of non-alcoholic fatty liver disease, according to various estimates, affects a quarter of the world population. Significant interest in this pathology is due to the high frequency of adverse liver (steatohepatitis, liver fibrosis and cirrhosis) and extrahepatic (association with cardiovascular disease) outcomes. One of the key areas is the timely diagnosis of liver steatosis. Reference diagnostic methods, which include liver biopsy and magnetic resonance imaging with assessment of liver fat proportion weighted by proton density, have objective practical and financial limitations for their routine use in detection and quantitative assessment of liver steatosis. Therefore, one of the current trends in hepatology is the development of inexpensive, widely applicable, and reliable noninvasive diagnostic tools. The aim of the present review is a comparative analysis of various ultrasound methods of liver steatosis diagnostics: qualitative, semi-quantitative and quantitative (estimation of hepatorenal index, controlled attenuation parameter). The presented publication reviews the currently available methods of detection and assessment of severity of liver steatosis based on ultrasound examination, including their classification, methodology and comparison of diagnostic efficiency with analysis of intra- and inter-operator reproducibility, sensitivity and specificity.

MRI Spectroscopy as a Diagnostic Model for Assessment of Liver Steatosis in NAFLD Non-Diabetic Patients

Abstract Background Non-alcoholic fatty liver disease, the hepatic pandemic of the XXI century, being the number one cause of chronic hepatic disease in the occidental world. Aim of the Work To evaluate the diagnostic performance of MRI spectroscopy for assessing hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) in non diabetic patients. Patients and Methods A case control study was conducted on 40 patients inhepatology and gastroenterology department & Radiology department ain shams university hospital from Jan 2020 to November 2020 to study role of MRI spectroscopy as adiagnostic model for assessment of liver steatosis in NAFLD non diabetic patients. Results There was statically significant Positive correlation Between hepatic steatosis score, fat peak and fat fraction %, and there was statically significant Negative correlation Between Hepatic steatosis score and water peak. Conclusion MRI Spectroscopy can be reliably used as an accurate and specific noninvasive method for the diagnosis of Nonalcoholic fatty Liver Disease.

Instrumental features of the differential diagnosis of metabolically associated and non-alcoholic fatty liver diseases

Taking into account the lack of consensus between different scientific groups on the nature and unity of the pathomorphological substrate of non-alcoholic and metabolically associated fatty liver diseases, there is a need to find new instrumental methods for their differential diagnosis in order to develop the correct treatment and monitoring tactics.Aim: To assess the possibilities of using the complex application of instrumental diagnostic methods for the differential diagnosis of metabolically associated and non-alcoholic fatty liver disease.Methodology and Methods. The study involved 94 patients of a multidisciplinary hospital with a combination of ultrasound signs of liver steatosis according to the B-mode. As part of the two stages of the diagnostic examination, clinical, laboratory and instrumental methods were used, including a block of ultrasound diagnostics (assessment of the thickness of visceral fat, quantitative liver steatometry, two-dimensional elastography of shear waves of the liver), dual-energy X-ray absorptiometry in the “Whole body” mode. The control group included 78 patients without signs of hepatic steatosis according to B-mode ultrasound.Results. All patients were divided into groups according to signs of metabolic syndrome, with subsequent distribution into conditional groups of patients with non-alcoholic and metabolically associated fatty liver disease, highlighting the main signs of both diseases. Metabolic syndrome was detected in 24 women (29.27%), 18 men (21.95%). In 53 patients (64.63%), the presence of hepatic steatosis was quantitatively confirmed, of which 39 patients were found to be overweight or obese (47.56%).Conclusion. Indicators of the instrumental assessment of the metabolic status and a complex diagnostic algorithm were determined, allowing for differential diagnosis between non-alcoholic and metabolically associated fatty liver disease with a quantitative assessment of liver steatosis.

Exploring the Potential Performance of Fibroscan for Predicting and Evaluating Metabolic Syndrome using a Feature Selected Strategy of Machine Learning.

Metabolic syndrome (MetS) includes several conditions that can increase an individual's predisposition to high-risk cardiovascular events, morbidity, and mortality. Non-alcoholic fatty liver disease (NAFLD) is a predominant cause of cirrhosis, which is a global indicator of liver transplantation and is considered the hepatic manifestation of MetS. FibroScan® provides an accurate and non-invasive method for assessing liver steatosis and fibrosis in patients with NAFLD, via a controlled attenuation parameter (CAP) and liver stiffness measurement (LSM or E) scores and has been widely used in current clinical practice. Several machine learning (ML) models with a recursive feature elimination (RFE) algorithm were applied to evaluate the importance of the CAP score. Analysis by ANOVA revealed that five symptoms at different CAP and E score levels were significant. All eight ML models had accuracy scores > 0.9, while treebags and random forest had the best kappa values (0.6439 and 0.6533, respectively). The CAP score was the most important variable in the seven ML models. Machine learning models with RFE demonstrated that using the CAP score to identify patients with MetS may be feasible. Thus, a combination of CAP scores and other significant biomarkers could be used for early detection in predicting MetS.

Diagnostic accuracy of computer morphometry for steatosis and fibrosis assessment in patients with chronic liver disease of various etiologies

Background. Accurate assessment of the fibrosis stage is crucial for effective treatment. Histological examination, the primary method used for assessing liver fibrosis, has certain limitations due to variation within each stage. Computer morphometry offers an objective and quantitative approach to complement histological analysis, providing additional diagnostic information. The purpose of this study was to analyze the computer morphometry data in patients with chronic liver diseases (CLD) of different etiologies and determine their diagnostic accuracy for liver fibrosis diagnosis. Materials and methods. Seventy-five patients with CLD, namely 24 with non-alcoholic fatty liver disease (NAFLD), 8 with alcoholic liver disease (ALD), 1 with toxic hepatitis, and 42 with chronic hepatitis C (CHC), were included in the study. Percutaneous liver biopsy was performed under ultrasound guidance using a semi-automatic needle Colt Shot 16 G. The severity of fibrosis was assessed using the Metavir scale. For computer morphometry, biopsies were photographed and evaluated using the ImageJ 1.45S program (National Institutes of Health, USA). The computerized fibrosis index (CFI), steatosis index, and the number of apoptotic cells in 5 consecutive high-power fields were calculated. Receiver operating characteristic analysis was performed for CFI diagnostic accuracy assessment. Results. Advanced liver fibrosis (F3-F4) was diagnosed in 62.5 % of ALD cases and 31.0 % of CHC. The highest CFI was found in ALD, it exceeded the level of NAFLD and CHC patients by 3.3 (p < 0.01) and 2 times (p < 0.05), respectively. At the same time, people with NAFLD had the highest steatosis index (0.36 ± 0.11), which was 1.7 times higher (p < 0.05) than in ALD and CHC. Moreover, CFI correlated with the fibrosis stage (r = 0.71, p < 0.05). Stage I of liver fibrosis according to the Metavir scale is characterized by CFI up to 0.040, stage II — 0.041–0.130, stage III — 0.131–0.219, and stage IV — more than 0.220. CFI cut-off value was 0.017, which confirms the presence of liver fibrosis in patients with chronic liver diseases regardless of the etiology (sensitivity — 85.2 %, specificity — 100.0 %). Conclusions. Computer morphometry significantly improves the accuracy and reliability of histological examination, and allows to objectify morphological assessment of liver steatosis and fibrosis and to ensure long-term storage of the results.

SAT-465 - High performance of serological indexes in the non-invasive assessment of liver steatosis

SAT-465 - High performance of serological indexes in the non-invasive assessment of liver steatosis

Simultaneous imaging of ultrasonic relative backscatter and attenuation coefficients for quantitative liver steatosis assessment

Prevalence of liver disease is continuously increasing and nonalcoholic fatty liver disease (NAFLD) is the most common etiology. We present an approach to detect the progression of liver steatosis based on quantitative ultrasound (QUS) imaging. This study was performed on a group of 55 rats that were subjected to a control or methionine and choline deficient (MCD) diet known to induce NAFLD. Ultrasound (US) measurements were performed at 2 and 6 weeks. Thereafter, animals were humanely euthanized and livers excised for histological analysis. Relative backscatter and attenuation coefficients were simultaneously estimated from the US data and envelope signal-to-noise ratio was calculated to train a regression model for: (1) fat fraction percentage estimation and (2) performing classification according to Brunt’s criteria in grades (0 <5%; 1, 5–33%; 2, >33–66%; 3, >66%) of liver steatosis. The trained regression model achieved an R^2 of 0.97 (p-value < 0.01) and a RMSE of 3.64. Moreover, the classification task reached an accuracy of 94.55%. Our results suggest that in vivo QUS is a promising noninvasive imaging modality for the early assessment of NAFLD.

WED-469 - Quantitative ultrasound for liver steatosis assessment: benefits of measurements over a large two-dimensional region of interest on the performance of image-brightness-based parameters

WED-469 - Quantitative ultrasound for liver steatosis assessment: benefits of measurements over a large two-dimensional region of interest on the performance of image-brightness-based parameters

Novelties on non-invasive scores for the assessment of liver steatosis.

Novelties on non-invasive scores for the assessment of liver steatosis.

Diagnostic performance of a novel ultrasound-based quantitative method to assess liver steatosis in histologically identified nonalcoholic fatty liver disease.

To investigate the diagnostic performance of ultrasound-guided attenuation parameter (UGAP) for the detection of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD) cohorts using histopathology as the reference standard andcomparing it with that of various imaging modalities. A total of 87 subjects who underwent UGAP, controlled attenuation parameter (CAP), and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) between December, 2020 and January, 2022 were enrolled. Of these patients, 38 patients had NAFLD. The association between UGAP and clinical and imaging parameters was assessed using Pearson's or Spearman's correlations. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. The UGAP and MRI-logPDFF demonstrated strong positive correlations (correlation coefficient= 0.704, P <0.0001). UGAP showed excellent diagnostic performance for distinguishing steatosis grade ≥1 with an AUROC of 0.821 (95% confidence interval [CI], 0.729-0.913), which was comparable to that of MRI-PDFF (0.829, 95%CI, 0.723-0.936). The AUROCs of BUSG (B-mode ultrasonography) (0.766, 95% CI, 0.767-0.856) and CAP (0.788, 95% CI, 0.684-0.891) were slightly lower than those of UGAP. The AUROCs of UGAP, MRI-PDFF, CAP, and BUSG for detecting steatosis grade ≥2 were 0.796 (95% CI, 0.616-0.975), 0.971 (95% CI, 0.936-1.000), 0.726 (95% CI, 0.561-0.891) and 0.774 (95% CI, 0.612-0.936), respectively. UGAP may be a valuable potential screening tool as a first-line assessment of liver steatosis in patients with NAFLD.

A New Combined Non-invasive Method for Assessment of Liver Steatosis and Fibrosis in NAFLD Patients – Pilot Study

The aim of this study was to investigate the clinical efficacy (sensitivity,  specificity) of ultrasound-based imaging methods for the assessment of fibrosis and steatosis in patients with non-àlcoholic fatty liver disease (NAFLD). Sixty-six patients with NAFLD and 43 healthy volunteers (control group) were tested. Liver biopsy was used as a reference method for the evaluation of NAFLD. Liver stiffness measurement (LSM) with transient elastography (TE) and two-dimensional shear wave elastography (2D-SWE) was used to assess fibrosis. Steatosis was assessed by Controlled Attenuation Parameter (CAP) and EchoLevels (ELs). Using the ELs, two hepato-renal indices were calculated – the hepato-renal index difference (HRIdiff) and hepato-renal index ratio (HRIratio). Additionally, one serum biomarker was calculated – APRI. Cut-offs of cirrhosis (F4) were defined as follows: ≥ 9.64 kPa and ≥ 9.85 kPa for 2D-SWE and TE. Only 2D-SWE had a correlation for significant fibrosis – the cut-off was ≥ 6.50 kPa and for lack of significant fibrosis (F &lt; 2) less than 5.26 kPa. Steatosis was diagnosed with a cut-off of 240.50 dB/m for CAP, and HRIdiff ≥ 0.39, and HRIratio ≤ 0.99 for ELs. Both types of SWE and the two methods for evaluation of ultrasound (US) attenuation have good correlation with fibrosis and steatosis in NAFLD.

Enhancing the accuracy of mid-infrared spectroscopy-based liver steatosis quantification using digital image analysis as a reference.

The assessment of liver steatosis is crucial in both hepatology and liver transplantation (LT) surgery. Steatosis can negatively impact the success of LT. Steatosis is a factor for excluding donated organs for LT, but the increasing demand for transplantable organs has led to the use of organs from marginal donors. The current standard for evaluating steatosis is a semi-quantitative grading based on the visual examination of a hematoxylin and eosin (H&E)-stained liver biopsy, but this method is time-consuming, subjective, and lacks reproducibility. Recent research has shown that infrared (IR) spectroscopy could be used as a real-time quantitative tool to assess steatosis during abdominal surgery. However, the development of IR-based methods has been hindered by the lack of appropriate quantitative reference values. In this study, we developed and validated digital image analysis methods for the quantitation of steatosis in H&E-stained liver sections using univariate and multivariate strategies including linear discriminant analysis (LDA), quadratic DA, logistic regression, partial least squares-DA (PLS-DA), and support vector machines. The analysis of 37 tissue samples with varying grades of steatosis demonstrates that digital image analysis provides accurate and reproducible reference values that improve the performance of IR spectroscopic models for steatosis quantification. A PLS model in the 1810-1052 cm-1 region using first derivative ATR-FTIR spectra provided RMSECV = 0.99%. The gained improvement in accuracy critically enhances the applicability of Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) to support an objective graft evaluation at the operation room, which might be especially relevant in cases of marginal liver donors to avoid unnecessary graft explantation.

Comparing the direct assessment of steatosis in liver explants with mid- and near-infrared vibrational spectroscopy, prior to organ transplantation.

A fast and accurate assessment of liver steatosis is crucial during liver transplantation surgery as it can negatively impact its success. Recent research has shown that near-infrared (NIR) and attenuated total reflectance-Fourier transform mid-infrared (ATR-FTIR) spectroscopy could be used as real-time quantitative tools to assess steatosis during abdominal surgery. Here, in the frame of a clinical study, we explore the performance of NIR and ATR-FTIR spectroscopy for the direct assessment of steatosis in liver tissues. Results show that both NIR and ATR-FTIR spectroscopy are able to quantify the % of steatosis with cross-validation errors of 1.4 and 1.6%, respectively. Furthermore, the two portable instruments used both provided results within seconds and can be placed inside an operating room evidencing the potential of IR spectroscopy for initial characterization of grafts in liver transplantation surgery. We also evaluated the complementarity of the spectral ranges through correlation spectroscopy.

Quantitative assessment of liver steatosis using ultrasound: dual-energy CT

Quantitative assessment of liver steatosis using ultrasound: dual-energy CT