Kento Imajo

Background/Objectives: The ultrasound-guided attenuation parameter (UGAP) is conventionally measured at a 4 cm start depth from the skin with a 4 cm region of interest (ROI), whereas 2024 World Federation for Ultrasound in Medicine and Biology (WFUMB) guidance recommends 2 cm from the liver capsule with a 3 cm ROI. We compared these two ROI configurations, applied to the same archived acquisitions, against MRI-derived proton density fat fraction (MRI-PDFF). Methods: This retrospective study included 565 patients with chronic liver disease from four of six participating Japanese centers at which raw data had been stored. Conventional UGAP was measured in real time; WFUMB-based values were calculated retrospectively from the same acquisitions, without real-time operator optimization. Performance was assessed by receiver operating characteristic analysis and the Obuchowski index, with integrated discrimination improvement (IDI) and net reclassification improvement (NRI) as secondary analyses. Results: Areas under the curve did not differ significantly at any threshold (≥S1: 0.92 [95% CI: 0.90–0.94] vs. 0.92 [0.89–0.94]; p = 0.07–0.23). Conventional UGAP correlated slightly more strongly with MRI-PDFF (ρ = 0.83 vs. 0.81; Δρ = 0.02; p < 0.01) and had a higher Obuchowski index (0.92 vs. 0.91; p = 0.04); both differences were statistically significant but of doubtful clinical relevance, and secondary IDI/NRI analyses were directionally consistent but imprecise. Body mass index was the strongest independent predictor of the inter-protocol difference. Conclusions: Neither ROI configuration showed a clinically meaningful advantage on this single-vendor platform. Small differences favoring the manufacturer-optimized configuration were not uniform across centers and may largely reflect acquisition asymmetry. No equivalence margin was prespecified, so these data show no demonstrable advantage for either configuration rather than establishing equivalence and require confirmation in a prospective paired study.

Background: No randomized controlled trial has directly compared the efficacy of pemafibrate to that of fenofibrate, or evaluated the dose–response relationship of pemafibrate in metabolic dysfunction–associated steatotic liver disease (MASLD). Therefore, we compared the efficacy and safety of high- and low-dose pemafibrate versus fenofibrate over 48 weeks in patients with MASLD and hypertriglyceridemia.Methods: This multicenter, open-label, randomized controlled trial included 360 patients with MASLD and hypertriglyceridemia at 29 sites in Japan. Participants were randomly assigned (1:1:1) to high-dose pemafibrate (0·4 mg/day; PEM-H), low-dose pemafibrate (0·2 mg/day; PEM-L), or fenofibrate (53·3-106·6 mg/day; FENO) groups. The primary endpoint was change in alanine aminotransferase (ALT) levels at Week 24. Secondary endpoints included liver fibrosis markers, renal parameters, magnetic resonance elastography (MRE), and adverse events.Findings: At Week 24, PEM-H and PEM-L produced significantly greater ALT reductions than FENO (p < 0·001 and p = 0·015, respectively). Exploratory comparison revealed greater reduction for PEM-H than PEM-L (p = 0·018, Holm adjustment), suggesting a dose-dependent effect. Higher baseline ALT levels and lean phenotypes were independently associated with ALT response. At Week 48, Mac-2 binding protein glycosylation isomer decreased significantly in PEM-H and PEM-L compared with a modest reduction in FENO (p < 0·001 and p < 0·001, respectively). MRE demonstrated significant decreases in liver stiffness in PEM-H and PEM-L compared with FENO (p < 0·05 and p = 0·02, respectively). Percentage change in serum creatinine levels was lower in PEM-H and PEM-L than in FENO. No treatment-related serious adverse events were observed in any of the three groups.Interpretations: Pemafibrate demonstrated greater reductions in ALT levels than fenofibrate, with a clear dose–response relationship and favorable safety profile, suggesting its therapeutic potential for patients with MASLD and hypertriglyceridemia.

Aim: Two‐dimensional shear wave elastography (2D‐SWE) is a non‐invasive technique for assessing liver fibrosis. However, its clinical utility has not been fully established. This study evaluated the diagnostic accuracy of 2D‐SWE using magnetic resonance elastography (MRE) as the reference standard in a retrospective, multicenter, large‐scale cohort. Methods: A total of 744 patients with chronic liver disease were included in the analysis. The association between 2D‐SWE measurements and fibrosis stages determined by MRE was assessed. The correlation between 2D‐SWE and MRE values was analyzed, and the diagnostic performance of 2D‐SWE was evaluated using receiver operating characteristic (ROC) curve analysis. Results: As 2D‐SWE and MRE values were not normally distributed, they were log‐transformed (Log‐2D‐SWE and Log‐MRE) for analysis. A strong correlation was observed between Log‐2D‐SWE and Log‐MRE values, with a correlation coefficient of 0.764 ( p < 0.001). When 2D‐SWE values were stratified according to the histological stages of liver fibrosis (F0–F4), based on MRE data, the corresponding median values were 4.61, 5.63, 6.18, 7.44, and 11.64 kPa, respectively ( p < 0.001, Jonckheere–Terpstra test). The areas under the ROC curve (AUROCs) and cutoff values for 2D‐SWE were 0.872 and 5.47 kPa for ≥ F1 ( n = 285), 0.894 and 5.88 kPa for ≥ F2 ( n = 217), 0.931 and 6.48 kPa for ≥ F3 ( n = 137), and 0.937 and 7.39 kPa for F4 ( n = 81), respectively. In subgroup analyses, AUROCs for detecting ≥ F2, ≥F3, and F4 exceeded 0.78, even among patients with elevated body mass index or advanced hepatic steatosis. Conclusions: 2D‐SWE represents a highly useful and reliable non‐invasive modality for assessing of liver fibrosis.

Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) exhibits marked heterogeneity in fibrosis progression and liver‐related outcomes. Liver biopsy is not feasible for longitudinal risk stratification at scale, creating a need for validated non‐invasive biomarkers, particularly imaging biomarkers, that can predict clinically meaningful disease progression and liver‐related outcomes. Aims: To describe the design and rationale of the GOLDMINE study, established to determine whether non‐invasive imaging biomarkers predict MASLD progression and liver‐related clinical outcomes. Methods: GOLDMINE is an investigator‐initiated, multi‐centre, international longitudinal cohort enrolling up to 1000 adults with either biopsy‐proven MASLD or MASLD cirrhosis across the full fibrosis spectrum. Participants are recruited from 15 sites in the US and 4 international sites (Japan, Singapore and France). At baseline, participants undergo clinical phenotyping, vibration‐controlled transient elastography, and advanced magnetic resonance imaging (MRI), including proton‐density‐fat‐fraction and magnetic resonance elastography (MRE). MRI (and biospecimen banking) is repeated at 2‐year intervals (years 2 and 4), with annual follow‐up visits for up to 10 years. Baseline liver histology is centrally processed, digitized and reviewed by a single expert hepatopathologist; all MRI/MREs are centrally interpreted. Results: The prespecified clinical outcomes include progression to cirrhosis, clinically significant portal hypertension, major adverse liver‐related outcomes (ascites, hepatic encephalopathy, portal hypertensive bleeding, liver transplantation/qualification), hepatocellular carcinoma, major adverse cardiovascular events, and all‐cause mortality, with independent central adjudication of all events. Conclusions: GOLDMINE establishes a rigorously phenotyped MASLD cohort integrating centralized histology, advanced MRI‐based biomarkers, longitudinal biobanking, and adjudicated outcomes, providing a platform to validate imaging and blood‐based prognostic biomarkers in MASLD.

Accurate non-invasive assessment of hepatic steatosis is essential in metabolic dysfunction-associated steatotic liver disease. This study aimed to compare the diagnostic performance of the ultrasound-guided attenuation parameter (UGAP) and Hamaguchi score (HS) using ordinal-scale-specific statistical methods, with magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) as the reference standard. This multicenter cross-sectional study enrolled 1,010 patients with chronic liver disease at six tertiary hepatology centers. UGAP and HS were compared against MRI-PDFF-defined steatosis grades (S0: < 5.2%, S1: 5.2- < 11.3%, S2: 11.3- < 17.1%, S3: ≥ 17.1%). Beyond conventional receiver operating characteristic (ROC) curve analysis, we applied the Adjusted Youden Index (AYI) for optimal cutoff determination across all ordinal categories and the Obuchowski measure (OM) for overall diagnostic accuracy assessment, incorporating penalties proportional to the magnitude of misclassification. UGAP demonstrated stronger correlation with MRI-PDFF than HS (Spearman's rank correlation coefficient ρ = 0.805 vs. 0.776, p < 0.001). ROC analysis demonstrated higher areas under the curve for UGAP across all thresholds, with a significant difference at ≥ S2 (0.912 vs. 0.884, p = 0.002). The overall OM was significantly higher for UGAP (0.907, 95% confidence interval [CI] 0.894-0.919) than HS (0.886, 95% CI 0.872-0.899, p = 0.002). AYI-derived cutoffs for UGAP were 0.63, 0.71, and 0.81 dB/cm/MHz for S1, S2, and S3, respectively. Ordinal-scale-specific methods demonstrate that UGAP provides superior diagnostic performance over conventional B-mode scoring, better reflecting graduated disease severity and the clinical consequences of misclassification. (University Hospital Medical Information Network000041196).

Background: Attenuation imaging (ATI) is used for the noninvasive diagnosis of hepatic steatosis (HS) based on the ultrasound system. However, the clinical utility of ATI has not yet been sufficiently evaluated. In this study, we used the magnetic resonance imaging‐based proton density fat fraction (MRI‐PDFF) as a reference standard to investigate the usefulness of ATI in diagnosing HS. Methods: We conducted a prospective multicenter study that included 1059 patients with chronic liver disease who underwent ATI and MRI‐PDFF. We defined the degree of steatosis as follows: S0, MRI‐PDFF < 5.2%; S1, 5.2% ≤ MRI‐PDFF < 11.3%; S2, 11.3% ≤ MRI‐PDFF < 17.1%; and S3, MRI‐PDFF ≥ 17.1%, based on previously published studies. Results: Because the MRI‐PDFF data were not normally distributed, log‐transformed data (log MRI‐PDFF) were used for the analyses. The correlation coefficient between ATI values and log MRI‐PDFF was high ( r = 0.779). A Bland–Altman analysis revealed that ATI values and log MRI‐PDFF showed good consistency with a mean bias of 0.000 and a narrow range of agreement (95% confidence interval [CI], −0.519–0.519). The areas under the receiver operating characteristic curve (95% CI) and cutoff values for ATI were 0.910 (0.893–0.928) and 0.65 dB/cm/MHz for ≥ S1 steatosis, 0.928 (0.913–0.944) and 0.69 dB/cm/MHz for ≥ S2 steatosis, and 0.913 (0.894–0.931) and 0.72 dB/cm/MHz for ≥ S3 steatosis, respectively. Conclusions: ATI is an excellent and beneficial noninvasive technique for the evaluation of HS. Trial Registration: UMIN Clinical Trials Registry (UMIN000048672)

Purpose: Hepatic steatosis, which is associated with liver diseases and adverse clinical outcomes, requires accurate, noninvasive diagnostic methods because of the limitations of liver biopsy. This study aimed to evaluate the effectiveness of the ultrasound-guided attenuation parameter (UGAP), a novel technique for assessing hepatic steatosis, and to compare its diagnostic performance with that of the controlled attenuation parameter (CAP), using magnetic resonance imaging (MRI)–derived proton density fat fraction (PDFF) as the reference standard.Methods: A total of 255 patients with chronic liver disease who underwent CAP, UGAP, and MRI-PDFF were prospectively enrolled from three liver centers in Japan. Using the area under the receiver operating characteristic curve (AUROC) analysis, cutoff values for UGAP were determined according to steatosis grades based on MRI-PDFF. To minimize overfitting, diagnostic performance was validated using five-fold cross-validation.Results: CAP and UGAP values followed normal distributions, whereas PDFF values deviated from normality and were therefore log-transformed, yielding the variable MRI-logPDFF. CAP and UGAP demonstrated significant correlations with MRI-logPDFF, with intraclass correlation coefficients of 0.696 and 0.797, respectively. For MRI-PDFF–based grading, the AUROC (95% confidence interval) values of CAP and UGAP were 0.878 (0.813–0.923) versus 0.926 (0.867–0.960) for S0 versus S1–S3 (P=0.041), 0.820 (0.763–0.865) versus 0.908 (0.861-0.940) for S0–S1 versus S2–S3 (P<0.001), and 0.863 (0.811–0.902) versus 0.897 (0.852-0.930) for S0–S2 versus S3 (P=0.128), respectively. The validation analysis produced results consistent with those of the primary cohort.Conclusion: UGAP showed greater diagnostic accuracy than CAP for hepatic steatosis, notably in detecting grades ≥S1 and ≥S2.

Introduction Non-alcoholic fatty liver disease, now known as metabolic dysfunction-associated steatotic liver disease (MASLD), is a phenotype of the metabolic syndrome in the liver and is clearly associated with metabolic abnormalities such as hyperglycaemia and dyslipidaemia. Although the prevalence of MASLD is increasing worldwide, there is currently no consensus on the efficacy and safety of the drugs used to treat MASLD/metabolic dysfunction-associated steatohepatitis (MASH). Pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was designed to have higher peroxisome proliferator-activated receptor alfa (PPARα) agonist activity and selectivity than existing PPARα agonists, and in development trials, without increasing creatinine levels, lipid parameters and alanine aminotransferase (ALT) were significantly improved. Thus, pemafibrate may effectively ameliorate the pathogenesis and metabolic abnormalities in MASLD/MASH. In this trial, we evaluated the efficacy and safety of pemafibrate in patients with MASLD/MASH. Methods and analysis This trial was designed as an open-label, three-arm, randomised controlled study. After obtaining informed consent, patients aged 20–80 years who met the selection criteria were enrolled. Patients were randomised to receive pemafibrate 0.4 mg/day, 0.2 mg/day or fenofibrate (n=120 per group). The duration of treatment was 48 weeks. The primary endpoint was a change in ALT levels after 24 weeks of administration. Secondary endpoints included changes from baseline in liver fibrosis markers (fibrosis-4 index, type IV collagen 7s, enhanced liver fibrosis and Mac-2 binding protein glycosylation isomer) at 48 weeks as well as changes in liver fat mass and liver stiffness measured by MRI and ultrasound (US) at centres equipped with MRI and US capabilities. Ethics and dissemination Ethical approval was obtained from the Yokohama City University Certified Institutional Review Board before participant enrolment (CRB20-014). The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences. Participants wishing to understand the results of this study will be contacted directly on data publication. Trial registration number This trial was registered in the Japan Registry of Clinical Trials (number: jRCTs031200280). Protocol version V.1.9, 23 November 2023

Although handheld ultrasound devices (HUDs) are commonplace, their ability to diagnose fecal retention (FR) remains unclear. This prospective observational study examined HUDs’ usefulness in diagnosing FR in patients with constipation in a palliative care setting. Between 10 December 2020 and 30 June 2022, we compared rectal ultrasonographic findings obtained using HUDs with clinical manifestations in 64 males and 70 females (48%, 52%, 68 ± 11 years old) with constipation who had undergone computed tomography (CT). FR was diagnosed using a HUD and compared with CT and digital rectal examination (DRE) results. In total, 42 (31%), 42 (31%), and 41 (31%) patients were diagnosed using HUDs, CT, and DRE, respectively. Thirty-nine (93%) patients in the CT group were also diagnosed with FR using HUDs. A total of 89 of 92 patients with a negative CT diagnosis also had a negative HUD diagnosis. Among the 41 patients in the DRE group, 37 were also diagnosed with FR using HUDs. Among 93 patients with a negative DRE diagnosis, 86 had a negative HUD diagnosis. The sensitivity, specificity, positive predictive value, and negative predictive value of HUDs for CT were 93%, 97%, 93%, and 97%, respectively. Those of HUDs for DRE were 88%, 94%, 86%, and 95%, respectively. The concordance rates for FR diagnosis were 128/134 for CT and HUDs and 123/134 for DRE and HUDs. HUD was useful for diagnosing FR in this setting. HUDs could provide valuable support for appropriate treatment selection. Developing a constipation treatment algorithm based on rectal ultrasonographic findings is warranted in the future.

Purpose: The effect of hepatic fibrosis stage on quantitative ultrasound based on the attenuation coefficient (AC) for liver lipid quantification is controversial. The objective of this study was to determine how the degree of fibrosis assessed by magnetic resonance (MR) elastography affects AC based on the ultrasound-guided attenuation parameter according to the grade of hepatic steatosis, using magnetic resonance imaging (MRI)–derived proton density fat fraction (MRIderived PDFF) as the reference standard.Methods: Between February 2020 and April 2021, 982 patients with chronic liver disease who underwent AC and MRI-derived PDFF measurement as well as MR elastography were enrolled. Multiple regression was used to investigate whether AC was affected by the degree of liver stiffness.Results: AC increased as liver stiffness progressed in 344 patients without hepatic steatosis (P=0.009). In multivariable analysis, AC was positively correlated with skin-capsule distance (P<0.001), MR elastography value (P=0.037), and MRI-derived PDFF (P<0.001) in patients without hepatic steatosis. In 52 of 982 patients (5%), the correlation between AC and MRIderived PDFF fell outside the 95% confidence interval for the regression line slope. Patients with MRI-derived PDFF lower than their AC (n=36) had higher fibrosis-4 scores, albumin-bilirubin scores, and MR elastography values than patients with MRI-derived PDFF greater than their AC (n=16; P=0.018, P=0.001, and P=0.011, respectively).Conclusion: AC is affected by liver fibrosis (MR elastography value ≥6.7 kPa) only in patients without hepatic steatosis (MRI-derived PDFF <5.2%). These values should be interpreted with caution in patients with advanced liver fibrosis.