Two-dimensional elastography and dispersion slope for allograft evaluation after pediatric liver transplantation

Jeong Min Song; In Hye Song; Hee Mang Yoon; Pyeong Hwa Kim; Ah Young Jung; Jin Seong Lee; Jung-Man Namgoong; Seak Hee Oh; Kyung Mo Kim; Young Ah Cho; Teresa Victoria

doi:10.14366/usg.25237

Song, Song, Yoon, Kim, Jung, Lee, Namgoong, Oh, Kim, Cho, and Victoria: Two-dimensional elastography and dispersion slope for allograft evaluation after pediatric liver transplantation

Original Article

Ultrasonography 2026; 45(4): 381-392. https://doi.org/10.14366/usg.25237

Two-dimensional elastography and dispersion slope for allograft evaluation after pediatric liver transplantation

Jeong Min Song¹^*

, In Hye Song²^*

, Hee Mang Yoon¹

, Pyeong Hwa Kim¹

, Ah Young Jung¹

, Jin Seong Lee¹

, Jung-Man Namgoong³

, Seak Hee Oh⁴

, Kyung Mo Kim⁴

, Young Ah Cho¹

, Teresa Victoria⁵

¹Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

²Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

³Department of Pediatric Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

⁴Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

⁵Department of Radiology, Massachusetts General Hospital, Boston, MA, USA

Correspondence to: Hee Mang Yoon, MD, PhD, Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel. +82-2-3010-4352 Fax. +82-2-476-4719 E-mail: espoirhm@gmail.com

*These authors contributed equally to this work.

Received November 15, 2025 Revised May 18, 2026 Accepted May 20, 2026 Published online May 20, 2026

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

This study evaluated the diagnostic performance of two-dimensional shear-wave elastography (2D SWE) for assessing allograft pathology in pediatric liver transplantation (LT) recipients, with subgroup analyses according to sonographic approach and age group. Additionally, the present study aimed to identify factors associated with SWE-derived parameters.

Methods

This study retrospectively analyzed pediatric LT recipients who had received a left lobe or left lateral segment graft during childhood and underwent paired 2D SWE and liver biopsy. Associations between elasticity and dispersion slope measurements and clinicopathologic parameters were evaluated using univariable and multivariable regression analyses. Subgroup analyses were performed according to sonographic approach and age group. Diagnostic performance was assessed using receiver operating characteristic analysis.

Results

A total of 108 patients (median age, 13.4 years; 47 males) were included. Elasticity measured using the intercostal approach in patients aged ≥13 years showed significant associations with METAVIR (Meta-analysis of Histological Data in Viral Hepatitis) fibrosis grade, necroinflammatory activity grade, liver allograft fibrosis score, and rejection activity index score. In multivariable analysis incorporating clinical parameters, METAVIR fibrosis grade remained the only independent predictor of intercostal elasticity in this age group (coefficient, 2.17; P<0.001). Intercostal elasticity demonstrated excellent diagnostic performance for distinguishing F0–F2 from F3–F4 fibrosis (area under the curve [AUC], 0.95; P<0.001; cut-off, 11.0 kPa) and good performance for distinguishing F0–F1 from F2–F4 fibrosis (AUC, 0.83; P<0.001; cut-off, 7.2 kPa). In contrast, subcostal measurements and dispersion slope showed no significant association with any pathologic parameter.

Conclusion

Intercostal elasticity demonstrated diagnostic value for predicting graft fibrosis in pediatric LT recipients aged ≥13 years who received left lobe or left lateral segment grafts. Among the evaluated clinicopathologic parameters, METAVIR fibrosis grade was the only independent predictor of elasticity in this subgroup.

Keywords: Liver transplantation; Child; Ultrasonography; Elastography; Follow-up studies

Key points

Intercostal elasticity may be a useful parameter for assessing graft fibrosis in pediatric liver transplant recipients aged ≥13 years. In these patients, METAVIR fibrosis grade was the only independent predictor of intercostal elasticity. Subcostal elasticity and shear-wave dispersion slope did not demonstrate diagnostic value for detecting histopathologic graft injury.

Graphical abstract

Introduction

Liver transplantation (LT) is considered the gold-standard curative treatment for children with end-stage liver disease, particularly biliary atresia [1]. Long-term outcomes after pediatric LT have generally been favorable [2,3]. However, liver allograft injury, particularly fibrosis, may develop because of multiple factors, even in asymptomatic patients [4]. If not identified and managed appropriately, such injury may adversely affect long-term outcomes and may ultimately result in increased mortality or the need for retransplantation [5–7].

Liver biopsy remains the reference standard for evaluating fibrosis in liver allografts [8,9]. As a noninvasive alternative, ultrasound elastography techniques such as shear-wave elastography (SWE) have been used to assess liver allograft stiffness. Previous studies in adults have demonstrated strong correlations between SWE-derived liver stiffness measurements and the histopathologic extent of graft fibrosis [10,11]. More recent studies have also investigated shear-wave dispersion slope, a parameter that reflects tissue viscosity, for assessing necroinflammatory activity in adult LT recipients, although its clinical utility remains uncertain [12,13].

Unlike adult recipients, who typically receive whole-liver or right lobe grafts, pediatric recipients commonly receive left lobe or left lateral segment grafts [14,15]. Consequently, the subcostal approach is frequently used during ultrasound examinations in pediatric recipients, particularly when the conventional intercostal approach is technically difficult [16–18]. These anatomic and technical differences may influence the diagnostic performance of ultrasound elastography-derived liver stiffness measurements in pediatric recipients.

Recent studies have investigated the ability of two-dimensional (2D) SWE to detect and assess liver fibrosis after pediatric LT [19–23]. Although these studies demonstrated that 2D SWE can distinguish clinically significant fibrosis, only one study reported diagnostic utility for mild fibrosis. In addition, one study attempted to evaluate the relationship between tissue inflammation and shear-wave dispersion slope; however, that analysis was limited by a small sample size [21]. Notably, no previous study has evaluated differences in diagnostic performance between the intercostal and subcostal approaches in pediatric LT recipients. Although one study reported no significant difference between the two approaches in children, the findings were based on healthy participants and were limited by a small sample size [24]. Furthermore, studies adequately evaluating the diagnostic performance of SWE across pediatric age groups remain limited despite substantial age-related heterogeneity in pediatric patients.

The primary aim of this study was to evaluate the diagnostic accuracy of 2D SWE for detecting allograft injury, including graft fibrosis, in pediatric recipients of left lobe or left lateral segment grafts. The present study also evaluated diagnostic performance according to ultrasound approach and age group. In addition, it aimed to identify clinicopathologic factors associated with SWE-derived parameters.

Materials and Methods

Compliance with Ethical Standards

This single-center study combined retrospective and prospective cohorts and was approved by the institutional review board. For the prospective cohort, both the study protocol and informed consent process were approved by the board, and written informed consent was obtained from all participants (S2020-2229-0009). For the retrospective cohort, the requirement for written informed consent was waived by the board (S2024-2157-0002). The study was designed and conducted in accordance with the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines [25].

Patients

Patients who underwent ultrasound-guided liver biopsy at the authors’ affiliated institution between February 2020 and April 2024 were identified. The inclusion criteria were as follows: (1) pediatric patients who had undergone LT and (2) recipients of a left lobe or left lateral segment graft. For patients who underwent multiple biopsies during the study period, only the first biopsy was included in the analysis. The exclusion criterion was the absence of 2D SWE performed immediately before liver biopsy. Data from February 2021 to November 2021 were obtained from a prospective liver biopsy registry. Additional consecutive eligible cases were retrospectively collected between February 2020 and April 2024, excluding the prospective registry enrollment period. The SWE acquisition technique, examiner assignments, imaging and biopsy procedures, and statistical analyses were identical between the retrospective and prospective cohorts; the study period represented the only difference between cohorts.

At the authors’ institution, liver biopsy was performed either according to a post-transplant surveillance protocol or in cases of clinically suspected liver allograft injury. Surveillance biopsies were typically obtained at predefined follow-up intervals, including before transition from the pediatric LT clinic to the adult LT clinic.

2D Shear-Wave Elastography

All included patients underwent 2D SWE immediately before liver biopsy using an Aplio i800 ultrasound scanner (Canon Medical Systems, Otawara, Japan) equipped with an i8CX1 convex probe. One of two board-certified pediatric radiologists performed both the 2D SWE examination and liver biopsy during the same session (P.H.K. and H.M.Y., with 4 and 8 years of experience in pediatric radiology, respectively). All patients fasted for at least 6 hours before the procedure. Elastography was performed with the patient in the supine position. The intercostal approach was used preferentially for 2D SWE. However, when an adequate sonic window could not be obtained because of intervening bowel loops, the subcostal approach was used instead. Patients were instructed to hold their breath during the examination whenever feasible, typically in those aged ≥5 years. When breath-holding was possible, measurements were obtained during suspended respiration while avoiding deep inspiration and Valsalva maneuver. The sample box was positioned 1–2 cm below the liver capsule to minimize reverberation artifacts. A circular region of interest was then placed in areas demonstrating smooth, parallel shear-wave propagation lines without visible vessels or artifacts, as confirmed on four reference maps: the elasticity map, propagation map, grayscale image, and shear-wave dispersion slope map [12,26]. A total of 13 measurements were obtained, and the median liver stiffness and dispersion slope values from at least 10 valid measurements, excluding outliers, were used for analysis. When the interquartile range (IQR)–to–median ratio exceeded 0.3, the measurements were considered unreliable and the acquisition process was repeated.

Liver Biopsy and Pathologic Examination

Ultrasound-guided percutaneous liver biopsy was performed immediately after the 2D SWE examination using an 18-gauge needle (Stericut biopsy needle; TSK Laboratory, Tochigi, Japan). Sedation was administered when necessary according to patient age and preference; in general, patients younger than 10 years underwent sedation. Liver biopsy was performed using either an intercostal or subcostal approach to target liver parenchyma as close as possible to the SWE measurement site. Two core liver specimens, each measuring 2 cm in length, were obtained. After biopsy, ultrasound-guided compression of the biopsy tract was performed for 5 minutes. Patients were then closely monitored for potential complications during the subsequent 24 hours.

Histopathologic evaluation of liver tissue specimens was performed by an experienced pathologist (I.H.S., with 11 years of experience in pathology) who was blinded to the patients’ clinical history, laboratory findings, imaging findings, and 2D SWE measurements. The following histopathologic parameters were assessed: METAVIR (Meta-analysis of Histological Data in Viral Hepatitis) fibrosis grade (F0–F4), necroinflammatory activity grade (A0–A3) [27], liver allograft fibrosis (LAF) score [28], and rejection activity index (RAI) score [29]. Additional findings, including cholangitis, chronic rejection, ischemic injury, and idiopathic post-transplantation hepatitis, were also evaluated, and allograft damage was considered present when any of these findings were identified. As previously described, the LAF score was determined by evaluating fibrosis within three anatomic compartments: portal tracts, sinusoids, and centrilobular veins [28]. Each compartment was assigned a score from 0 to 3 according to fibrosis severity, and the component scores were summed to generate a total LAF score ranging from 0 to 9. To assess acute cellular rejection, the RAI score was calculated by grading inflammatory changes across three distinct histologic regions: portal tracts, bile ducts, and subendothelial zones. Each of these parameters received a score from 0 to 3 based on severity, culminating in a cumulative index ranging from 0 to 9.

Statistical Analysis

Univariable regression analysis was performed to identify pathologic parameters associated with liver elasticity or dispersion slope measurements, including METAVIR fibrosis grade, necroinflammatory activity grade, LAF score, RAI score, and allograft damage. Subgroup analyses were conducted according to ultrasound approach (intercostal versus subcostal) and age group (<6 years, 6 to <13 years, and ≥13 years). Univariable and multivariable analyses were also performed to identify independent clinical and pathologic predictors of elastographic parameters. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of SWE parameters for clinically significant pathologic conditions. For the liver allograft fibrosis (LAF) score, because there is no established clinical consensus on a single optimal cutoff, the scores were dichotomized using multiple exploratory thresholds (e.g., total LAF score ≥3 or ≥4, or a score ≥2 in any individual anatomic compartment) to evaluate diagnostic performance. Area under the curve (AUC) values were interpreted as follows: 0.90–1.00, excellent; 0.80–0.89, good; 0.70–0.79, fair; 0.60–0.69, poor; and 0.50–0.59, failed discrimination [30,31]. Cut-off values for SWE parameters were determined by maximizing the Youden index. Univariable and multivariable ordinal logistic regression analyses were additionally used to assess associations between SWE parameters and histopathologic measures. Variables with P<0.1 in univariable analysis were entered into multivariable models, which were subsequently refined using stepwise selection. All statistical analyses were performed using Python version 3.12 (Python Software Foundation, Wilmington, DE, USA) and R version 4.5.1 (R Foundation for Statistical Computing, Vienna, Austria; https://www.R-project.org). Statistical significance was defined as a two-sided P-value <0.05.

Results

Patients

A total of 224 liver biopsies performed in 199 patients between February 2020 and April 2024 were identified. Among these, 83 cases without liver transplantation, 16 cases involving grafts other than left liver grafts, and 14 repeat biopsies from previously included patients were excluded according to the eligibility criteria, leaving 111 liver biopsies from 111 patients. Of these, three patients who did not undergo 2D SWE immediately before biopsy were further excluded, resulting in a final study population of 108 liver biopsies from 108 patients (Fig. 1). Among the included patients, 10 were prospectively enrolled and 98 were retrospectively included. Baseline characteristics of the study population are summarized in Table 1. The median age at SWE was 13.4 years (IQR, 7.0 to 16.6 years), and the male-to-female ratio was 47:61. The median interval between LT and biopsy was 11.4 years (IQR, 3.8 to 15.4 years). Biliary atresia was the most common indication for LT, accounting for 63.9% of cases (69/108), followed by acute liver failure (12.0%, 13/108). Significant fibrosis (≥ F2) was observed in 28.7% of patients (31/108), whereas severe fibrosis (F3 and F4) was identified in only 1.9% (2/108). In addition, 46.3% of patients (50/108) had a necroinflammatory activity grade of ≥A1, and 36.1% (39/108) demonstrated allograft injury. Liver biopsy was performed as part of protocol-based surveillance in 45.4% of patients (49/108) and for suspected allograft injury in 54.6% (59/108). Suspected allograft injury was more common among patients younger than 13 years (38/52) than among those aged ≥13 years (21/56). Comparisons between the retrospective and prospective cohorts are presented in Supplementary Table 1.

Association between SWE and Pathologic Parameters

Among the 108 patients, SWE was performed using the intercostal approach in 72 patients and the subcostal approach in 36 patients. All 10 prospectively enrolled patients underwent examination using the subcostal approach because an adequate intercostal acoustic window could not be obtained. No cases remained unreliable after repeat sampling, and no patients were excluded because of failure to satisfy the IQR-to-median reliability criterion. Accordingly, there were no technical failures in elasticity or dispersion slope measurements. Baseline characteristics according to examination approach are summarized in Supplementary Table 2. Representative SWE images obtained using the intercostal and subcostal approaches are shown in Fig. 2.

The results of the univariable linear regression analyses evaluating associations between pathologic parameters and 2D SWE measurements are summarized in Table 2. In the overall cohort (n=108), elasticity was significantly associated with METAVIR fibrosis grade (coefficient [standard error (SE)], 1.08 [0.36]; P=0.003) and LAF score (coefficient [SE], 0.36 [0.16]; P=0.030). Subgroup analysis according to scanning approach demonstrated that elasticity measured using the intercostal approach was significantly associated with METAVIR fibrosis grade (coefficient [SE], 1.65 [0.49]; P=0.001) and LAF score (coefficient [SE], 0.51 [0.21]; P=0.018). In contrast, dispersion slope was not significantly associated with any pathologic parameter in either the intercostal or subcostal subgroup.

Age-stratified subgroup analysis was performed only within the intercostal cohort because of the small number of patients and the absence of significant associations between elasticity and pathologic parameters in the subcostal cohort (Table 3). Among the age-stratified subgroups, only patients aged ≥13 years demonstrated significant associations between elasticity and pathologic parameters, including METAVIR fibrosis grade, LAF score, necroinflammatory activity grade, and RAI score. In this subgroup, dispersion slope showed a statistically significant inverse association with allograft injury. No significant associations between elastographic and pathologic parameters were identified in the younger age groups. Complementary univariable logistic regression analyses, in which pathologic parameters were modeled as dependent variables and SWE parameters as predictors, are presented in Supplementary Tables 3 and 4. Additional subgroup analyses according to biopsy indication (routine surveillance versus suspected allograft injury) were also performed in both the overall cohort and the intercostal subgroup (Supplementary Tables 5 and 6). In both analyses, liver elasticity was significantly associated with METAVIR fibrosis grade only in patients who underwent routine surveillance biopsy.

To identify factors independently associated with elasticity measured using the intercostal approach in patients aged ≥13 years, univariable and multivariable regression analyses were performed (Table 4). Evaluated variables included clinical and laboratory parameters, as well as pathologic variables that demonstrated significant associations with elasticity in univariable analysis. Because of substantial multicollinearity between fibrosis scoring systems, METAVIR fibrosis grade was selected instead of LAF score as the fibrosis variable in the multivariable model. In multivariable analysis, only METAVIR fibrosis grade remained independently associated with elasticity (coefficient [SE], 2.17 [0.49]; P<0.001).

Diagnostic Performance of SWE

The results of the ROC analysis evaluating the diagnostic performance of elasticity for hepatic fibrosis in patients aged ≥13 years are summarized in Table 5 and Supplementary Fig. 1. The AUC increased with increasing fibrosis severity. Elasticity demonstrated excellent diagnostic performance for differentiating METAVIR F3–F4 fibrosis from F0–F2 fibrosis (AUC, 0.95; P<0.001; cut-off, 11.0 kPa), although this estimate should be interpreted cautiously because only two patients had severe fibrosis. Elasticity also demonstrated good diagnostic performance for identifying ≥F2 fibrosis (AUC, 0.83; P<0.001; cut-off, 7.2 kPa). In addition, intercostal elasticity demonstrated fair diagnostic performance for distinguishing patients with a total LAF score ≥4 (AUC, 0.78; P<0.001; cut-off, 7.6 kPa).

Discussion

This study evaluated the diagnostic performance of elasticity and dispersion slope obtained using 2D SWE for assessing liver allograft injury in pediatric LT recipients who received left lobe or left lateral segment grafts. Its findings demonstrated that elasticity measured using the intercostal approach was useful for assessing graft fibrosis in patients aged ≥13 years, whereas shear-wave dispersion slope showed limited clinical utility. To the authors’ knowledge, this study represents one of the largest cohorts evaluating the diagnostic performance of 2D SWE for graft fibrosis and inflammation in pediatric LT recipients. In addition, all patients underwent same-day ultrasonography and biopsy, and the cohort consisted exclusively of recipients of left-sided grafts, which strengthens the internal consistency of the study despite the relatively limited sample size.

The principal finding of this study was that liver elasticity measured using the intercostal approach was significantly associated with graft fibrosis in patients aged ≥13 years, whereas elasticity measured using the subcostal approach was not significantly associated with graft fibrosis or inflammation. Diagnostic performance was highest for differentiating severe fibrosis (F3–F4) from lower fibrosis stages (F0–F2), with an AUC of 0.95 and a cut-off value of 11.0 kPa. However, this estimate should be interpreted cautiously because only two patients had F3–F4 fibrosis. For the detection of clinically significant fibrosis (F2–F4), which may be more relevant in clinical practice [32,33], elasticity demonstrated good diagnostic performance, with an AUC of 0.83 and a cut-off value of 7.2 kPa.

Several previous studies have investigated optimal SWE cut-off values for identifying significant fibrosis in adult and pediatric LT recipients. Deurdulian et al. [10] suggested a cut-off value of 9.3 kPa (1.76 m/s) for distinguishing METAVIR F0–F1 fibrosis from F2–F4 fibrosis in adult LT recipients. In pediatric LT recipients, Kehler et al. [20] proposed a cut-off value of 7.6 kPa (1.59 m/s) for identifying clinically significant fibrosis (≥F2), which is comparable to the value identified in this study [34]. However, the present analysis specifically focused on pediatric LT recipients stratified according to age group and ultrasound approach, thereby providing a more targeted reference framework for this population.

In addition, this study evaluated liver fibrosis using the LAF score, whereas most previous studies relied on the METAVIR grading system, which was originally developed to assess portal fibrosis in chronic hepatitis C [27]. In contrast, the LAF scoring system was specifically developed for pediatric LT recipients and evaluates fibrosis across three anatomic compartments: portal tracts, sinusoids, and centrilobular veins [28]. This approach may provide a more comprehensive assessment of chronic allograft injury [35]. In the present study, 2D SWE demonstrated fair diagnostic performance for distinguishing patients with a total LAF score of 0–3 from those with a score ≥4, with an AUC of 0.78. Further large-scale clinical and radiologic studies are warranted to clarify the clinical relevance of the LAF scoring system and the role of elastography in predicting LAF-related allograft injury.

In comparisons of ultrasound approaches, only the intercostal approach demonstrated significant associations with graft fibrosis. Previous studies have used the subcostal approach as an alternative because of anatomic constraints and graft positioning in pediatric patients [16–18]. However, the present findings suggest that reliance on the subcostal approach may reduce diagnostic accuracy. This observation may partly reflect the younger age distribution in the subcostal subgroup, which could influence examination quality because of anatomic factors and reduced procedural cooperation. In addition, several technical factors related to ultrasound examination, including probe pressure and probe-to-target distance, are known to affect elastography measurements [34,36,37]. Subcostal elastographic measurements of the left liver are particularly susceptible to bowel gas interference, probe-compression artifacts, and cardiac or respiratory motion [38–40]. Nevertheless, evaluation using the intercostal approach may also be technically challenging when the allograft is centrally located or when bowel loops intervene between the ultrasound probe and the graft. In such cases, the left intercostal approach may still provide an alternative route for elasticity measurement. For patients in whom only the subcostal approach is feasible, elasticity measurements should therefore be interpreted cautiously. Further large-scale studies are needed to evaluate the clinical utility of the subcostal approach for assessing LAF and injury in pediatric LT recipients.

In the age-stratified analysis, significant associations between liver elasticity and pathologic parameters were observed only in patients aged ≥13 years, whereas no significant associations were identified in patients aged <6 years or 6 to <13 years. This finding may partly reflect the relatively small sample sizes in the younger age groups, which may have limited statistical power. Another important contributor to the observed age-dependent differences may relate to technical aspects of elastography acquisition. Because pediatric-sized probes do not support dispersion slope measurements, an adult-sized convex transducer was used in all patients, including younger children. Use of a transducer not optimized for smaller body size may have affected SWE measurements in younger patients and may partly explain why significant associations were observed only in older patients. In addition, several pediatric-specific factors, including smaller body size, narrower intercostal spaces, limited breath-holding ability, and reduced examination cooperation, may have influenced measurement quality. The observed age-related differences may also reflect differences in clinical indications for biopsy. Suspected allograft injury was more common among patients younger than 13 years (38/52 [73.1%]) than among those aged ≥13 years (21/56 [37.5%]), whereas older patients more frequently underwent routine surveillance biopsy (35/56 [62.5%] versus 14/52 [26.9%]). Consistent with this observation, a significant association between liver elasticity and fibrosis grade was identified only in patients undergoing routine surveillance biopsy, suggesting that acute inflammatory changes related to rejection may confound elastography measurements and obscure their relationship with chronic fibrosis. Further investigation is warranted to evaluate the diagnostic utility of SWE-derived parameters in younger pediatric age groups.

Shear-wave dispersion slope was not significantly associated with any evaluated pathologic parameter. Although a statistically significant inverse association between dispersion slope and allograft injury was observed in patients aged ≥13 years, the direction of this association contrasts with findings from previous studies [12,41]. Lee et al. [12] reported positive associations between dispersion slope and both graft fibrosis and necroinflammatory activity in adult LT recipients, whereas Sugimoto et al. [42] demonstrated significant diagnostic utility for detecting lobular inflammation in adult nonalcoholic steatohepatitis. In contrast, Zhang et al. [13] found that dispersion slope provided no additional benefit beyond liver stiffness for distinguishing fibrosis from necroinflammatory activity. Notably, none of these previous studies reported an inverse association, raising uncertainty regarding the clinical significance of the subgroup finding of this study. The discrepancy may reflect differences in patient age, underlying hepatic disease, or technical factors related to SWE acquisition. Further studies are warranted to clarify the clinical role of shear-wave dispersion slope in pediatric LT recipients.

This study has several limitations. First, this was a single-center study that combined retrospective and prospective cohorts. Although identical eligibility criteria and examination protocols were applied, the requirement for informed consent in the prospective cohort may have introduced selection bias. Second, the sample size was relatively small, reflecting the low frequency of pediatric LT. Nevertheless, this study included one of the largest cohorts evaluating the diagnostic performance of 2D SWE and shear-wave dispersion slope in pediatric LT recipients. Third, some patients were unable to perform breath-holding during examination, and the effects of breath-holding on image quality and measurement accuracy were not specifically evaluated. Fourth, direct comparison between intercostal and subcostal measurements within individual patients was not possible. SWE acquisition was intentionally limited to a single clinically feasible approach per patient to reduce examination burden and maintain procedural feasibility in pediatric patients. Although direct within-patient comparison between approaches would have been desirable, this was not feasible in the present cohort. In addition, SWE was performed using an adult-sized convex transducer in all patients, which may have affected measurement performance in younger children with smaller body size. Because pediatric-sized probes do not currently support dispersion slope measurements, use of an adult transducer was unavoidable. Finally, hepatic congestion was not evaluated as an independent histopathologic variable. In routine liver allograft biopsy practice, hepatic congestion is often difficult to distinguish reliably from hemorrhagic or sinusoidal changes and is not consistently quantified using a validated scoring system. Consequently, reliable categorical classification was not feasible in this retrospective cohort.

In conclusion, liver elasticity measured using the intercostal 2D SWE approach demonstrated diagnostic value for identifying graft fibrosis in pediatric LT recipients aged ≥13 years. In this subgroup, METAVIR fibrosis grade was the only independent predictor of elasticity. In contrast, elasticity measured using the subcostal approach and shear-wave dispersion slope did not demonstrate significant clinical associations with graft fibrosis, inflammation, or allograft injury. In addition, SWE measurements in patients younger than 13 years did not provide clinically useful discrimination for histopathologic graft injury. These findings suggest that 2D SWE may help identify low-risk patients who could defer liver biopsy; however, further prospective studies with larger cohorts are needed to validate these findings.

Author Contributions

Conceptualization: Song JM, Song IH, Yoon HM, Kim PH. Data acquisition: Song IH, Yoon HM, Kim PH. Data analysis or interpretation: Song JM, Song IH, Yoon HM, Kim PH, Jung AY, Lee JS, Namgoong JM, Oh SH, Kim KM, Cho YA, Victoria T. Drafting of the manuscript: Song JM, Yoon HM, Kim PH. Critical revision of the manuscript: Song IH, Yoon HM, Jung AY, Lee JS, Namgoong JM, Oh SH, Kim KM, Cho YA, Victoria T. Approval of the final version of the manuscript: all authors.

Conflict of Interest

This research was funded by Canon Medical Systems Corporation. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no other competing interests.

Supplementary Material

Supplementary Table 1.

Comparison of baseline characteristics of the retrospective and prospective cohort (https://doi.org/10.14366/usg.25237).

usg-25237-Supplementary-Table-1.pdf

Supplementary Table 2.

Comparison of baseline characteristics of the intercostal and subcostal group (https://doi.org/10.14366/usg.25237).

usg-25237-Supplementary-Table-2.pdf

Supplementary Table 3.

Summary of univariable regression analyses of histopathologic outcomes using SWE parameters as predictors (https://doi.org/10.14366/usg.25237).

usg-25237-Supplementary-Table-3.pdf

Supplementary Table 4.

Univariable regression analyses of histopathologic outcomes using SWE parameters as predictors, stratified by age group in patients examined using the intercostal approach (https://doi.org/10.14366/usg.25237).

usg-25237-Supplementary-Table-4.pdf

Supplementary Table 5.

Regression analysis of pathologic factors associated with 2D shear-wave elastography metrics, stratified by biopsy indication (all patients) (https://doi.org/10.14366/usg.25237).

usg-25237-Supplementary-Table-5.pdf

Supplementary Table 6.

Regression analysis of pathologic factors associated with 2D shear-wave elastography metrics, stratified by biopsy indication (intercostal group) (https://doi.org/10.14366/usg.25237).

usg-25237-Supplementary-Table-6.pdf

Supplementary Fig. 1.

ROC curves showing the diagnostic performance of elasticity values measured via the intercostal approach in patients aged ≥13 years for the discrimination between METAVIR (https://doi.org/10.14366/usg.25237).

usg-25237-Supplementary-Fig-1.pdf

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Fig. 1.

Flowchart of patient selection.

Fig. 2.

Representative shear-wave elastography images obtained using the intercostal and subcostal approaches.

A. A 13-year-old girl with biliary atresia who underwent liver transplantation at 2 years of age and was evaluated as part of routine post-transplant surveillance presented. Two-dimensional shear-wave elastography demonstrated liver elasticity of 6.6 kPa and a dispersion slope of 11.9 (m/s)/kHz. Histopathologic examination demonstrated no fibrosis (METAVIR fibrosis grade F0), and all other pathologic findings were within normal limits (Intercostal scan). B. A 17-year-old girl with Wilson disease who underwent liver transplantation at 5 years of age and was evaluated because of suspected rejection presented. Two-dimensional shear-wave elastography demonstrated liver elasticity of 7.5 kPa and a dispersion slope of 13.1 (m/s)/kHz. Histopathologic examination demonstrated severe necroinflammatory activity (A3) with evidence of T-cell–mediated rejection, whereas no fibrosis was identified. In all examinations, measurements were obtained from liver parenchyma while avoiding vascular structures (subcostal scan).

Table 1.

Baseline characteristics of the study population (n=108)

Characteristic	Value
Age at US (year)	13.4 (7.0–16.6)
Age at LT (year)	1.2 (0.8–2.8)
Interval from LT to US (year)	11.4 (3.8–15.4)
Sex
Male	47 (43.5)
Female	61 (56.5)
Indication for LT
Biliary atresia	69 (63.9)
Acute liver failure	13 (12.0)
Malignancy	8 (7.4)
Metabolic disease	7 (6.5)
PFIC	5 (4.6)
Portal vein anomaly	2 (1.9)
Other	4 (3.7)
Laboratory findings at US
Platelet count (×10³/μL)	219.1±71.6
INR	1.0±0.1
Total bilirubin (mg/dL)	0.5±0.8
γ-GT (IU/L)	47.2±202.2
AST (IU/L)	47.4±156.2
ALT (IU/L)	48.3±207.5
ALP (IU/L)	196.7±234.0
Albumin (g/dL)	3.6±0.5
Pathologic parameters
METAVIR fibrosis grade
F0	32 (29.6)
F1	45 (41.7)
F2	29 (26.9)
F3	1 (0.9)
F4	1 (0.9)
Necroinflammatory activity grade
A0	58 (53.7)
A1	35 (32.4)
A2	9 (8.3)
A3	6 (5.6)
LAF score	2.8±1.9
RAI score	1.6±2.3
Allograft damage
No	69 (63.9)
Yes	39 (36.1)

Values are presented as median (IQR), number (%), or mean±SD.

US, ultrasonography; LT, liver transplantation; PFIC, progressive familial intrahepatic cholestasis; INR, international normalized ratio; γ-GT, gamma-glutamyl transferase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; METAVIR, Meta-analysis of Histological Data in Viral Hepatitis; LAF, liver allograft fibrosis; RAI, rejection activity index; IQR, interquartile range; SD, standard deviation.

Table 2.

Univariable regression analyses of pathologic parameters associated with two-dimensional shear-wave elastography measurements

Pathologic parameter	Subcostal scan (n=36)		Intercostal scan (n=72)		Total (n=108)
Pathologic parameter	Coefficient (SE)	P-value	Coefficient (SE)	P-value	Coefficient (SE)	P-value
Elasticity
METAVIR fibrosis grade	−0.30 (0.35)	0.403	1.65 (0.49)	0.001	1.08 (0.36)	0.003
LAF score	−0.09 (0.16)	0.585	0.51 (0.21)	0.018	0.36 (0.16)	0.030
Necroinflammatory activity grade	0.06 (0.29)	0.837	0.66 (0.55)	0.239	0.37 (0.36)	0.312
RAI score	–0.03 (0.12)	0.831	0.31 (0.20)	0.120	0.16 (0.13)	0.234
Allograft damage	0.11 (0.57)	0.839	1.30 (0.92)	0.163	0.81 (0.64)	0.211
Dispersion slope
METAVIR fibrosis grade	−0.40 (0.40)	0.331	−0.26 (0.42)	0.531	−0.29 (0.31)	0.344
LAF score	0.12 (0.19)	0.530	−0.15 (0.18)	0.388	−0.08 (0.14)	0.570
Necroinflammatory activity grade	0.24 (0.34)	0.466	−0.61 (0.44)	0.171	−0.26 (0.30)	0.398
RAI score	0.05 (0.13)	0.729	–0.17 (0.16)	0.275	–0.09 (0.11)	0.431
Allograft damage	1.10 (0.63)	0.089	−0.76 (0.74)	0.310	−0.12 (0.53)	0.818

Coefficients were calculated using univariable linear regression analysis, with pathologic parameters as the independent variables and the median elasticity value or dispersion slope values from two-dimensional shear wave elastography as the outcome variable.

All 10 patients in the prospective cohort were included in the subcostal group.

SE, standard error; METAVIR, Meta-analysis of Histological Data in Viral Hepatitis; LAF, liver allograft fibrosis; RAI, rejection activity index.

Table 3.

Univariable analysis stratified by age group in the intercostal cohort (n=72)

Pathologic parameter	Age < 6 (years) (n = 10)		6 ≤ Age < 13 (years) (n = 17)		Age ≥ 13 (years) (n = 45)
Pathologic parameter	Coefficient (SE)	P-value	Coefficient (SE)	P-value	Coefficient (SE)	P-value
Elasticity
METAVIR fibrosis grade	0.45 (1.12)	0.701	–0.08 (1.72)	0.956	2.17 (0.49)	<0.001
LAF score	1.10 (0.58)	0.088	–0.31 (0.62)	0.628	0.72 (0.23)	0.003
Necroinflammatory activity grade	–1.64 (1.48)	0.297	–0.20 (1.16)	0.871	1.72 (0.69)	0.017
RAI score	–0.09 (1.11)	0.432	0.17 (0.43)	0.690	0.56 (0.26)	0.036
Allograft damage	1.40 (1.51)	0.375	3.44 (2.26)	0.146	1.28 (1.32)	0.340
Dispersion slope
METAVIR fibrosis grade	0.93 (1.11)	0.428	–0.19 (0.92)	0.843	–0.27 (0.53)	0.610
LAF score	1.02 (0.61)	0.140	–0.33 (0.32)	0.324	–0.09 (0.23)	0.692
Necroinflammatory activity grade	–0.76 (1.60)	0.653	–0.11 (0.62)	0.861	–0.99 (0.65)	0.135
RAI score	0.38 (0.41)	0.377	–0.02 (0.23)	0.950	–0.42 (0.24)	0.079
Allograft damage	1.77 (1.49)	0.271	1.05 (1.28)	0.432	–3.31 (1.09)	0.004

SE, standard error; METAVIR, Meta-analysis of Histological Data in Viral Hepatitis; LAF, liver allograft fibrosis; RAI, rejection activity index.

Table 4.

Univariable and multivariable analyses identifying independent clinical or pathologic predictors for hepatic elasticity by intercostal approach in patients aged ≥13 years

Factor	Univariable analysis		Multivariable analysis
Factor	Coefficient (SE)	P-value	Coefficient (SE)	P-value
Age at US (year)	–0.01 (0.11)	0.935	-	-
Male sex	0.27 (1.07)	0.801	-	-
Age at LT (year)	–0.01 (0.11)	0.515	-	-
Interval from LT to US (year)	0.04 (0.11)	0.689	-	-
Platelet count (×10³/μL)	0.00 (0.01)	0.608	-	-
INR^a)	11.64 (6.46)	0.078	-	-
Total bilirubin (mg/dL)	1.11 (0.91)	0.229	-	-
γ-GT (IU/L)	0.00 (0.00)	0.912	-	-
AST (IU/L)	0.01 (0.02)	0.527	-	-
ALT (IU/L)	0.01 (0.01)	0.452	-	-
ALP (IU/L)	0.00 (0.01)	0.756	-	-
Albumin (g/dL)	–0.98 (1.16)	0.402	-	-
Pathologic parameters
METAVIR fibrosis grade	2.17 (0.49)	<0.001	2.17 (0.49)	<0.001
Total LAF score^a)	0.72 (0.23)	0.003	-	-
Necroinflammatory activity grade^a)	1.72 (0.69)	0.017	-	-
RAI score^a)	0.56 (0.26)	0.036	-	-

SE, standard error; US, ultrasonography; LT, liver transplantation; INR, international normalized ratio; γ-GT, gamma-glutamyl transferase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; METAVIR, Meta-analysis of Histological Data in Viral Hepatitis; LAF, liver allograft fibrosis; RAI, rejection activity index.

^a)Variables with P<0.1 in univariable analysis were included in the stepwise multivariable model. The total LAF score was excluded from the multivariable model due to substantial multicollinearity with METAVIR fibrosis score. Variables that did not remain statistically significant during stepwise selection were excluded and are indicated as ‘not included.’

Table 5.

Diagnostic performance of elasticity measured using the intercostal approach for hepatic fibrosis in patients aged ≥13 years

	Cut-off value (kPa)	Sensitivity (%)	Specificity (%)	AUC	P-value
METAVIR fibrosis grade
≥F1–F4 (n=33)	5.9	78 (62–89)	67 (39–86)	0.75 (0.60–0.90)	0.001
≥F2–F4 (n=14)	7.2	71 (45–88)	84 (67–93)	0.83 (0.69–0.98)	<0.001
≥F3–F4 (n=2)^a)	11	100 (34–100)	93 (81–98)	0.95 (0.75–1.00)	<0.001
LAF score^b)
Total LAF ≥3 (n=25)	7.5	48 (30–67)	95 (76–99)	0.73 (0.72–0.73)	<0.001
Total LAF ≥4 (n=20)	7.6	55 (34–74)	96 (81–99)	0.78 (0.63–0.92)	<0.001
Any LAF ≥2 (n=23)	7.6	48 (29–67)	96 (78–99)	0.75 (0.74–0.75)	<0.001

AUC, area under the curve; METAVIR, Meta-analysis of Histological Data in Viral Hepatitis; LAF, liver allograft fibrosis.

^a)For the F3–F4 category, diagnostic performance estimates should be interpreted with caution due to the very small number of cases (n=2), which may result in statistically unstable estimates. ^b)Multiple LAF thresholds were presented because there is currently no established clinical consensus regarding the optimal cutoff for clinically meaningful LAF. The total LAF score is the sum of three components (portal, sinusoidal, and centrilobular areas, each scored 0–3). "Any LAF ≥2" indicates at least one component score ≥2.