Ultrasound-guided attenuation parameter for identifying metabolic dysfunction-associated steatotic liver disease: a prospective study
Article information
Abstract
Purpose
This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard.
Methods
Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated.
Results
Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001).
Conclusion
Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.
Introduction
Steatotic liver disease (SLD) is the most common etiology of chronic liver disease, with a prevalence of approximately 30% worldwide [1]. SLD encompasses a range of conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD). Unlike prior terms, MASLD is defined by affirmative criteria rather than by exclusion, with a focus on hepatic steatosis arising from metabolic disorders. MASLD is commonly associated with overweight, obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus [2]. Patients with MASLD face a heightened risk of developing liver fibrosis, cirrhosis, and even hepatocellular carcinoma [3].
According to the diagnostic criteria, hepatic steatosis should be initially identified through biopsy or imaging techniques. Magnetic resonance imaging proton density fat fraction (MRI-PDFF) has been recognized as an accurate alternative imaging biomarker and is recommended by the World Federation of Ultrasound in Medicine and Biology (WFUMB) [4]. However, its routine use is limited by high costs and contraindications.
B-mode ultrasound (BMUS) is more commonly used in clinical practice, particularly for screening and monitoring, due to its accessibility, affordability, and lack of ionizing radiation [5,6]. However, BMUS is less sensitive in detecting mild hepatic steatosis due to its qualitative nature and operator dependence [5]. To better diagnose hepatic steatosis, quantitative ultrasound techniques have been developed [7]. The controlled attenuation parameter (CAP) represents the first approved technique used to quantify hepatic steatosis by measuring attenuation. The WFUMB position paper has endorsed CAP for point-of-care use [5]. However, CAP measurements are confined to A-mode and are less informative for higher grades of hepatic steatosis [5]. Such assessment may be more available for clinical practice if ultrasound devices could integrate quantitative ultrasound technologies.
The ultrasound-guided attenuation parameter (UGAP) is a quantitative metric that measures attenuation, thereby providing a quantitative assessment of hepatic steatosis. This measurement is integrated with BMUS imaging to visualize the liver parenchyma [5]. Several studies have shown that UGAP is accurate in diagnosing non-alcoholic fatty liver disease (NAFLD), with results that correlate well with histological or MRI-PDFF steatosis grading [8-11].
However, its efficacy in evaluating MASLD remains relatively unclear. This prospective study aims to evaluate the performance of UGAP in diagnosing hepatic steatosis within a selected and homogeneous cohort of patients with MASLD, using MRI-PDFF as the reference method. CAP was also measured in some patients to explore its correlation with UGAP and assess its diagnostic performance in MASLD.
Materials and Methods
Compliance with Ethical Standards
This prospective study received approval from the relevant institutional review board of Xinhua Hospital (XHEC-C-2022-091-3), and all participants provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki and the Declaration of Istanbul.
Study Design
Patients with or suspected of having hepatic steatosis, evaluated using BMUS (from the health care center) or CAP (from the Department of Gastroenterology), were enrolled in this study. The inclusion criteria were as follows: (1) patients aged 18 years or older who met at least one of the cardiometabolic criteria based on a multi-society Delphi consensus statement and were diagnosed with MASLD [2]; (2) patients who underwent UGAP measurements; and (3) patients scheduled for MRI-PDFF measurements for use as the reference standard for diagnosing hepatic steatosis. The exclusion criteria were as follows: (1) patients who did not receive valid UGAP or MRI-PDFF examinations; (2) patients with excessive alcohol consumption (more than 20 g/day for women and more than 30 g/day for men in the past 6 months); (3) patients with other causes of liver diseases, such as chronic hepatitis (indicated by positive hepatitis B surface antigen or anti-hepatitis C virus results), histological or etiological evidence of alternative liver diseases (for instance, autoimmune liver disease), or drug-induced hepatic steatosis; (4) patients who were pregnant or breastfeeding; and (5) patients who declined to participate in this study.
Ultrasound Examination and UGAP Measurement
The patients fasted for 6 hours before ultrasound examination. Prior to UGAP measurement, several liver characteristics were assessed using BMUS, including liver size, morphology, echogenicity, the clarity of intrahepatic venous borders, the diaphragm, and the skin-to-capsule distance.
UGAP measurements were obtained 1 week before MRI-PDFF assessments by a radiologist with over 15 years of experience in liver ultrasound scanning. These measurements were taken using a LOGIQ E10 ultrasound system (GE Healthcare, Wauwatosa, WI, USA) with a C1-6-D probe (1-6 MHz). For the procedure, patients lay in a supine position with their right arm fully abducted. The probe was positioned perpendicularly to the liver capsule via a right intercostal approach. During a calm breathing cycle, patients were instructed to hold their breath while videos displaying color-coded attenuation maps in hepatic segments V or VIII were recorded. Quality maps guided the adjustment of regions of interest (ROIs) within a homogeneous area on the attenuation map. Care was taken to avoid major intrahepatic vessels, bile ducts, rib shadows, and other artifacts. The ROIs were standardized in size, shape, and depth at 4 cm. Each patient underwent six UGAP measurements [12], and the system automatically calculated and stored a median UGAP value (expressed in dB/cm/MHz) for analysis. UGAP measurements were deemed valid if the ratio of the interquartile range (IQR) to the median was less than 0.30.
MRI-PDFF Examination
MRI examinations were conducted using a 3.0-T system (Ingenia, Philips, Eindhoven, Netherlands). The MRI-PDFF measurements employed a multi-echo Dixon technique. Custom algorithms generated MRI-PDFF maps from the multi-echo source images by simultaneously estimating T2* and PDFF, considering the multi-frequency interference from protons in liver fat [13,14]. To determine MRI-PDFF, a trained radiologist, who was blinded to the ultrasound findings, placed circular ROIs with a 2 cm diameter on each of the nine Couinaud hepatic segments. These were positioned at least 1.5 cm beneath the liver capsule, avoiding major blood vessels and artifacts [4]. A mean MRI-PDFF value, expressed as a percentage, was then calculated from these nine ROIs for subsequent analysis [15].
The MRI-PDFF cutoff values for each steatosis grade were as follows: <5% indicated absent hepatic steatosis (S0); ≥5% denoted mild hepatic steatosis (≥S1); ≥15% represented moderate hepatic steatosis (≥S2); and ≥25% indicated severe hepatic steatosis (S3) [16].
CAP Measurement
CAP assessment was performed 1 week prior to UGAP measurement by an experienced physician, utilizing the FibroScan 502 Touch system (Echosens, Paris, France). Patients had fasted for 6 hours or more and lay in a supine position with full abduction of their right arm. The measurements were taken via an intercostal approach on the right lobe of the liver. Selection of the M probe (3.5 MHz) or XL probe (2.5 MHz) was determined using an automated probe selection tool [17]. The median value was derived from 10 valid CAP measurements, and the results were expressed in dB/m. CAP measurement failure was recorded if no valid value could be obtained after a minimum of 10 attempts.
Statistical Analysis
Based on data from a previous study [8], sample sizes of 72 and 88 patients were calculated to detect a 20% difference in sensitivity and specificity between hepatic steatosis grades S0 and ≥S1, as determined by MRI-PDFF, using a two-sided test with 80% power and a 95% confidence interval (CI). Consequently, a sample size of 88 patients was chosen. To account for an anticipated 10% dropout rate, recruitment of 96 patients was planned.
Continuous data were expressed as either the median with IQR or the mean±standard deviation, as appropriate. Categorical data were presented as frequencies and percentages. Group comparisons for continuous data were analyzed using the Kruskal-Wallis test. The chi-square test was employed for categorical data. Spearman correlation analysis was utilized to compare UGAP with clinical metabolic parameters, MRI-PDFF, and CAP. The correlation coefficient (r) was categorized as very low (0 to 0.2), low (0.2 to 0.4), moderate (0.4 to 0.6), high (0.6 to 0.8) or very high (0.8 to 1). Multivariate linear regression was performed to identify factors significantly associated with UGAP values. Intraclass correlation coefficients (ICCs) with 95% CIs were calculated using a two-way mixed model to assess the consistency of UGAP measurements across different body mass index (BMI) categories (<25 kg/m2, ≥25 kg/m2 and <30 kg/m2, and ≥30 kg/m2) and various degrees of hepatic steatosis. An ICC below 0.4 was deemed poor, from 0.40 to 0.59 fair, from 0.60 to 0.74 good, and 0.75 or higher excellent. The diagnostic performance of UGAP and CAP measurements was evaluated using the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, and positive and negative predictive values, with MRI-PDFF serving as the reference standard. The DeLong test was applied to compare the AUCs of UGAP and CAP. The Youden index was utilized to determine the optimal cutoff value of UGAP for diagnosing hepatic steatosis. Analyses were conducted using SPSS version 29.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism version 9.4.1 (GraphPad Software Inc., La Jolla, CA, USA). A two-tailed P-value of ≤0.05 was considered to indicate statistical significance.
Results
Patient Characteristics
From July 2023 to June 2024, 97 patients were included in the study. Nine patients were excluded because they did not meet the cardiometabolic criteria (n=4) or exhibited prolonged alcohol overuse (n=5). Consequently, 88 patients (median age, 40 years [IQR, 36 to 46 years]; 54.5% [48/88] male and 45.5% [40/88] female) were included in the analysis (Fig. 1). Using MRI-PDFF as the reference for evaluating hepatic steatosis, the distribution of steatosis among the 88 patients was as follows: 20 (22.7%) had S0, 44 (50.0%) had S1, 19 (21.6%) had S2, and five (5.7%) had S3. The characteristics of the 88 patients are detailed in Table 1.
Derivation of the study cohort.
MRI-PDFF, magnetic resonance imaging proton density fat fraction; UGAP, ultrasound-guided attenuation parameter.
Characteristics of 88 patients with MASLD
Overview of UGAP Measurements
UGAP yielded valid measurements (as indicated by an IQR/median ratio of less than 0.30) in all 88 patients, and no instances of technical failure occurred. In the overall cohort, the median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/cm/MHz). The quality indicator of UGAP, namely the IQR/median ratio, was 0.07 (IQR, 0.04 to 0.11), and the measured skin-to-capsule distance using BMUS was 2.60 cm (IQR, 2.30 to 2.90 cm).
UGAP Values in Relation to Hepatic Steatosis as Evaluated by MRI-PDFF
Using MRI-PDFF as the reference for grading hepatic steatosis, the median UGAP values were as follows: 0.57 dB/cm/MHz (IQR, 0.54 to 0.66 dB/cm/MHz) for S0, 0.71 dB/cm/MHz (IQR, 0.68 to 0.80 dB/cm/MHz) for S1, 0.82 dB/cm/MHz (IQR, 0.78 to 0.90 dB/cm/MHz) for S2, and 0.86 dB/cm/MHz (IQR, 0.84 to 0.89 dB/cm/MHz) for S3. Pairwise comparisons revealed significant differences in median UGAP values between all grades of hepatic steatosis (P<0.05) except for S2 and S3 (Fig. 2). Furthermore, UGAP values demonstrated a positive correlation with MRI-PDFF (r=0.77; 95% CI, 0.66 to 0.85; P<0.001) (Fig. 3).
Box plots illustrating the distribution of ultrasoundguided attenuation parameter (UGAP) in relation to magnetic resonance imaging proton density fat fraction, which served as the reference standard for diagnosing hepatic steatosis grade.
The boxes indicate the interquartile range (25th to 75th percentiles), the whiskers extend from the minimum to the maximum values, and the dots represent outliers. *P<0.05, **P<0.01; NS, not significant.
Correlation between ultrasound-guided attenuation parameter (UGAP) and magnetic resonance imaging proton density fat fraction (MRI-PDFF).
Diagnostic Performance of UGAP in Grading Hepatic Steatosis
Using MRI-PDFF ≥5% as the diagnostic criterion for hepatic steatosis grade ≥S1, the AUC for UGAP was 0.91 (95% CI, 0.83 to 0.98). The optimal cutoff value was determined to be 0.67 dB/cm/MHz, yielding a sensitivity of 86.8% (95% CI, 76.7% to 92.9%) and a specificity of 90.0% (95% CI, 69.9% to 98.2%) (Fig. 4A). When using MRI-PDFF ≥15% to diagnose hepatic steatosis grade ≥S2, the AUC for UGAP was 0.90 (95% CI, 0.84 to 0.96), with a cutoff value of 0.76 dB/cm/MHz. This corresponded to sensitivity and specificity values of 91.7% (95% CI, 74.2% to 98.5%) and 78.1% (95% CI, 66.6% to 86.5%), respectively (Fig. 4B). For the diagnosis of hepatic steatosis grade S3 using MRI-PDFF ≥25%, the AUC for UGAP was 0.88 (95% CI, 0.80 to 0.95), with a cutoff value of 0.82 dB/cm/MHz. The sensitivity was 100% (95% CI, 56.6% to 100%), and the specificity was 75.9% (95% CI, 65.7% to 83.8%) (Fig. 4C). The receiver operating characteristic curves are presented in Fig. 5.
Ultrasound-guided attenuation parameter (UGAP) measurements guided by B-mode ultrasound images (left), presented with the corresponding attenuation map (right).
A. A 45-year-old man with grade S1 hepatic steatosis exhibited a median UGAP value of 0.70 dB/cm/MHz. B. A 33-year-old man with grade S2 hepatic steatosis displayed a median UGAP value of 0.77 dB/cm/MHz. C. A 45-year-old woman with grade S3 hepatic steatosis presented a median UGAP value of 0.95 dB/cm/MHz.
Area under the receiver operating characteristic curves (AUCs) for ultrasound-guided attenuation parameter (UGAP) in diagnosing hepatic steatosis grade.
When using magnetic resonance imaging proton density fat fraction thresholds of ≥5%, ≥15%, and ≥25% as references, the AUCs for UGAP in detecting hepatic steatosis grades ≥S1, ≥S2, and S3 were 0.91 (95% confidence interval [CI], 0.83 to 0.98), 0.90 (95% CI, 0.84 to 0.96), and 0.88 (95% CI, 0.80 to 0.95), respectively.
Correlation between UGAP and Clinical Metabolic Parameters
UGAP values demonstrated significant positive correlations with several parameters: alanine aminotransferase (ALT) level (r=0.44; 95% CI, 0.25 to 0.60; P<0.001), skin-to-capsule distance on BMUS (r=0.44; 95% CI, 0.24 to 0.59; P<0.001), BMI (r=0.39; 95% CI, 0.19 to 0.56; P<0.001), waist circumference (r=0.37; 95% CI, 0.17 to 0.54; P<0.001), and levels of triglycerides (TG) (r=0.37; 95% CI, 0.17 to 0.54; P<0.001), gamma-glutamyl transferase (GGT) (r=0.36; 95% CI, 0.16 to 0.54; P<0.001), and aspartate aminotransferase (AST) (r=0.26; 95% CI, 0.05 to 0.45; P=0.014). Conversely, UGAP values displayed a significant negative correlation with high-density lipoprotein cholesterol (HDL-C) level (r=-0.34; 95% CI, -0.51 to -0.13; P=0.001).
Factors Associated with UGAP Values
Multivariate linear regression analysis revealed that GGT level (odds ratio [OR], 0.001; P=0.045) and MRI-PDFF (OR, 0.010; P<0.001) were significantly associated with UGAP values (Supplementary Table 1).
Repeatability of UGAP Measurements
The ICC for UGAP measurements (six acquisitions per patient) across all patients was 0.80 (95% CI, 0.75 to 0.85; P<0.001). The ICCs of UGAP measurements were also evaluated across different BMI ranges. For patients whose BMI was under 25 kg/m2, the ICC was 0.86 (95% CI, 0.77 to 0.93; P<0.001). For those who had a BMI of 25 kg/m2 or higher but less than 30 kg/m2, the ICC was 0.73 (95% CI, 0.62 to 0.83; P<0.001). For patients with a BMI of 30 kg/m2 or higher, the ICC was 0.78 (95% CI, 0.66 to 0.88; P<0.001). Furthermore, the ICCs of UGAP measurements were assessed across different degrees of hepatic steatosis. The ICCs for patients with hepatic steatosis grades S0, S1, S2, and S3 were 0.78 (95% CI, 0.64 to 0.89; P<0.001), 0.59 (95% CI, 0.47 to 0.72; P<0.001), 0.66 (95% CI, 0.49 to 0.82; P<0.001), and 0.32 (95% CI, 0.02 to 0.84; P=0.018), respectively.
Comparison of UGAP and CAP in the Detection of Hepatic Steatosis
In a subgroup of 61 patients with MASLD who underwent UGAP, CAP, and MRI-PDFF measurements, 60 patients had valid CAP values, yielding a success rate of 98.4% (60/61) for CAP measurement. Representative images from one patient are shown in Fig. 6.
A 34-year-old woman with metabolic dysfunction-associated steatotic liver disease and a body mass index of 31.2 kg/m2.
A. The ultrasound-guided attenuation parameter image displays a value of 0.82 dB/cm/MHz. B. The magnetic resonance imaging proton density fat fraction image indicates a mean value of 20.0%. C. The controlled attenuation parameter image closest to the reported value was selected as representative, with a value of 333 dB/m.
In the subgroup with valid CAP measurements, 20.0% (12/60) of patients had hepatic steatosis grade S0, 51.7% (31/60) had grade S1, 25.0% (15/60) had grade S2, and 3.3% (2/60) had grade S3, as determined using MRI-PDFF as the reference standard. The distribution of CAP values using this reference standard is presented in Supplementary Table 2 and Supplementary Fig. 1. A positive correlation was noted between UGAP and CAP values (r=0.65; 95% CI, 0.47 to 0.78; P<0.001). Using MRI-PDFF as the reference, the diagnostic performances of UGAP and CAP for detecting hepatic steatosis were compared (Table 2). The cutoff values for UGAP in diagnosing hepatic steatosis grades ≥S1, ≥S2, and S3 were 0.62 dB/cm/MHz, 0.76 dB/cm/MHz, and 0.82 dB/cm/MHz, respectively. The corresponding CAP cutoff values were 295 dB/m, 322 dB/m, and 352 dB/m. For the detection of hepatic steatosis grade ≥S1, the AUCs for UGAP and CAP were 0.89 (95% CI, 0.77 to 1.00) and 0.94 (95% CI, 0.88 to 1.00), respectively. For grade ≥S2, the AUCs were 0.85 (95% CI, 0.76 to 0.95) for UGAP and 0.80 (95% CI, 0.67 to 0.92) for CAP. For grade S3, the AUCs were 0.82 (95% CI, 0.71 to 0.93) for UGAP and 0.91 (95% CI, 0.79 to 1.00) for CAP. However, no significant differences in diagnostic performance were observed between UGAP and CAP for hepatic steatosis grades ≥S1, ≥S2, and S3 (P>0.05).
Subgroup analysis comparing the performance between UGAP and CAP measurements for diagnosing and grading hepatic steatosis
Discussion
Metabolic dysfunction affects the course of steatotic liver disease, meaning that patients with MASLD tend to progress more rapidly or severely than those without metabolic disorders. It is essential to identify MASLD patients early, even though they often exhibit no liver-related symptoms [5]. Few studies have explored the use of imaging ultrasound systems equipped with attenuation coefficient algorithms for the assessment of MASLD. In the present study, as MRI-PDFF increased, the UGAP value also rose, demonstrating a highly significant positive correlation with MRI-PDFF. UGAP exhibited excellent sensitivity and specificity in the diagnosis and grading of hepatic steatosis, with MRI-PDFF employed as the reference.
MRI-PDFF, the reference standard used, accurately quantifies hepatic steatosis. However, its high cost makes it impractical for widespread use among patients. UGAP, an ultrasound-based tool, overcomes the disadvantages of MRI-PDFF measurement. In this study, the integration of UGAP with BMUS imaging yielded no technical failures during measurement. UGAP enables the adjustment of ROI positions in real time, using attenuation maps and quality maps superimposed on the liver parenchyma to avoid confounders and artifacts [5]. Additionally, UGAP measurements can be acquired using a standard ultrasound system and convex probe, without the need for extra equipment.
UGAP has been reported to correlate well with MRI-PDFF in patients who have chronic liver disease, with correlation coefficients ranging from 0.72 to 0.75 [10,18,19]. The present study also showed a positive correlation between UGAP and MRI-PDFF (r=0.77), with MRI-PDFF being significantly associated with UGAP. UGAP demonstrated good diagnostic performance (AUC, 0.88 to 0.91) when MRI-PDFF was employed as the reference standard. These findings align with a previous study [8] that included 1010 patients with chronic liver disease and revealed that UGAP has excellent diagnostic performance (AUC, 0.89 to 0.91) for grading steatosis; in that research, MRI-PDFF was similarly used as the reference (≥S1, MRI-PDFF ≥5.2%, ≥S2, MRI-PDFF ≥11.3%, and S3, MRI-PDFF ≥17.1%). Cannella et al. [20] recently conducted a study that included 100 patients with biopsy-proven MASLD, and found that UGAP had satisfactory diagnostic performance for detecting hepatic steatosis, with AUCs ranging from 0.78 to 0.82. The study also reported excellent interoperator and intraoperator reliability for UGAP measurements, with ICCs of 0.92 and 0.95, respectively. Furthermore, another recent study by Byenfeldt et al. [21], involving 60 patients with MASLD, demonstrated that increased probe force led to higher diagnostic performance of UGAP. Specifically, women in a 30° left decubitus position achieved an AUC of 0.93, while men in a supine position achieved an AUC of 0.91, both compared with MRI-PDFF. These results suggest that UGAP could serve as a potential monitoring biomarker in patients with MASLD.
Since few reports have compared the accuracy of UGAP and CAP within a given cohort, the present study incorporated the analysis of a subgroup of patients with MASLD who underwent UGAP, CAP, and MRI-PDFF measurements. UGAP and CAP values exhibited a high positive correlation (r=0.65). In previous research, Bende et al. [22] enrolled 179 participants with or without chronic liver disease (primarily NAFLD) and assessed UGAP measurements using CAP as the reference method (≥S1, CAP ≥230 dB/m; ≥S2, CAP ≥275 dB/m; and S3, CAP ≥300 dB/m). Their findings indicated a positive correlation between UGAP and CAP values (r=0.73) [22]. Similarly, Kuroda et al. [23] studied 105 patients with histopathologically confirmed NAFLD and also reported a high positive correlation between UGAP and CAP (r=0.68). In this study, using MRI-PDFF as the reference standard, the diagnostic performances of UGAP and CAP for detecting hepatic steatosis were compared in this subgroup. Both UGAP and CAP demonstrated good diagnostic accuracy for diagnosing and grading hepatic steatosis (AUC, 0.80 to 0.94). However, no significant differences in diagnostic performance were found (P>0.05). In a separate study, Fujiwara et al. [11] evaluated the diagnostic accuracy of UGAP in detecting hepatic steatosis compared to CAP, enrolling 163 patients with chronic liver disease who had undergone liver biopsy as the gold standard. They found that UGAP exhibited better performance (AUC, 0.95) than CAP (AUC, 0.84) in identifying steatosis grade ≥S2 (P=0.013). The discrepancy in findings could stem from the small sample size of the present cohort (only 60 patients) who underwent CAP measurements. Additionally, the success rate of CAP measurement was 98.4%, with no technical failures of UGAP measurement. Considering these findings, UGAP could serve as a potential alternative point-of-care tool in clinical practice when CAP measurements cannot be obtained.
UGAP values have demonstrated associations with clinical characteristics such as BMI (r=0.501), skin-to-capsule distance (r=0.413), and ALT (r=0.358) [8]. The present study also indicated significant correlations between UGAP values and metabolic parameters (including ALT, TG, GGT, AST, and HDL-C levels), body composition measures (BMI and waist circumference), and skin-to-capsule distance as measured on BMUS. ALT exhibited the highest correlation with UGAP (r=0.44). ALT levels are positively associated with increasing hepatic steatosis grade [24]. According to practice guidance from the American Association for the Study of Liver Diseases, a decrease in ALT level of ≥17 U/L is indicative of a histological response [25]. Consequently, UGAP values may provide value by dynamically reflecting changes in serum biomarkers.
Several limitations of this study should be acknowledged. First, the sample size was small, as it included only patients with MASLD from a single center. Consequently, the potential for selection bias cannot be ignored. Nonetheless, the sample size was determined based on previous research [8], supporting the reliability of the results. Second, while UGAP measurements demonstrated good to excellent repeatability across different BMI levels, the repeatability varied among degrees of hepatic steatosis. The poor ICC observed for UGAP measurements in patients with grade S3 hepatic steatosis may be explained by the presence of relatively few patients with this grade of steatosis. Future research involving a larger sample of patients with higher grades of hepatic steatosis is warranted to corroborate the results. Third, hepatic steatosis was assessed using MRI-PDFF as the reference method, rather than liver biopsy. This approach precludes the ability to correlate UGAP values with the precise amount of hepatic steatosis determined by pathology. To validate the results, multi-center studies with larger cohorts and liver biopsy as the reference standard are necessary.
In conclusion, UGAP demonstrates good diagnostic performance in detecting and grading hepatic steatosis in patients with MASLD, with MRI-PDFF used as the reference standard.
Notes
Author Contributions
Conceptualization: Huang YL, Sun C, Fan JG, Dong Y. Data acquisition: Huang YL, Sun C, Wang Y, Cheng J, Wang SW, Wei L, Fan JG. Data analysis or interpretation: Huang YL, Sun C, Lu XY, Cheng R, Wang M, Fan JG, Dong Y. Drafting of the manuscript: Huang YL, Sun C, Wang Y, Cheng J, Wang SW, Wei L, Lu XY, Cheng R, Wang M, Dong Y. Critical revision of the manuscript: Fan JG, Dong Y. Approval of the final version of the manuscript: all authors.
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Acknowledgments
This project was supported by the Sino-German Mobility Program of NSFC and DFG (Grant No. M-0504) and the National Natural Science Foundation of China (Grant No. 82071942).
Supplementary Material
Determinant factors for UGAP value (https://doi.org/10.14366/usg.24204).
values according to the hepatic steatosis evaluated by MRI-PDFF https://doi.org/10.14366/usg.24204).
Box plots showing the distribution of controlled attenuation parameter (CAP) according to magnetic resonance imaging proton density fat fraction as reference for the diagnosis of hepatic steatosis grade https://doi.org/10.14366/usg.24204).
References
Article information Continued
Notes
Key point
Ultrasound-guided attenuation parameter (UGAP) values demonstrated a highly significant positive correlation with magnetic resonance imaging proton density fat fraction (MRI-PDFF). With MRI-PDFF as a reference, UGAP displayed excellent diagnostic performance in the detection and grading of hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease. UGAP measurement could provide another option for point-of-care assessments, since its diagnostic performance is comparable to that of controlled attenuation parameter.