Yutaka Yasui

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/Objectives: Upadacitinib is recommended for moderate-to-severe ulcerative colitis (UC); however, data regarding its effectiveness and long-term outcomes in large patient populations remain limited. In this nationwide, hospital-based cohort study, we investigated the effectiveness and long-term outcomes of upadacitinib in patients with UC. Methods: This study included 2694 patients with UC who received upadacitinib. The primary outcome was the comparison of hospitalization rates during the 1-year periods before and after the initiation of upadacitinib. Additionally, the cumulative hospitalization rate up to 2 years post-initiation was evaluated. Results: Of 2694 patients who were initiated on upadacitinib, the median age was 45 (31–57) years, and 60.5% were male. In the year preceding upadacitinib initiation, 29.3% of the patients were hospitalized due to UC. In the 1 year following upadacitinib initiation, the hospitalization rate significantly decreased to 9.6% (p < 0.001). Furthermore, the cumulative hospitalization rate up to 2 years was 12.6%. Among patients with a prior history of hospitalization, the hospitalization rate in the 1 year after upadacitinib initiation decreased from 100% to 16.8%. A significant improvement in the hospitalization rate was observed in both advanced therapy-naïve and -exposed patients. After adjusting for age, sex, steroid use, and history of advanced therapy, the hazard ratio (95% confidence interval) for hospitalization associated with upadacitinib initiation was 0.39 (0.33–0.46, p < 0.001). Conclusions: The initiation of upadacitinib was associated with significantly lower hospitalization rates, and this association was maintained for up to two years. These findings support upadacitinib as an effective and viable treatment option for patients with moderate-to-severe UC.

Background/Objectives: Magnetic resonance elastography (MRE) provides an accurate and reproducible non-invasive assessment of liver stiffness and fibrosis severity in metabolic dysfunction-associated steatotic liver disease (MASLD). Although longitudinal changes in liver stiffness have been associated with clinical outcomes, the association between short-term and longitudinal changes remains unclear. This study aimed to evaluate the association between short-term and long-term changes in MRE-derived liver stiffness in patients with MASLD undergoing serial MRE assessments. Methods: In this retrospective cohort study, 100 patients with MASLD who underwent three MRE examinations at approximately baseline, 1 year, and 3 years were analyzed. Early response was defined as a ≥19% reduction in liver stiffness at the second examination relative to baseline. The association between early response and long-term liver stiffness changes was evaluated using logistic regression analysis. Results: A total of 22 patients (22%) were classified as early responders. Early responders were significantly more likely to achieve a ≥19% reduction in liver stiffness at the third MRE compared with non-early responders (59% vs. 27%, p = 0.006). In multivariable analysis adjusting for baseline liver stiffness, early response remained independently associated with long-term improvement (odds ratio 3.41, 95% CI 1.18–9.86; p = 0.023). Higher baseline liver stiffness was also associated with subsequent improvement (OR per 1 kPa increase, 1.44, 95% CI 1.11–1.87; p = 0.006). Conclusions: Early reductions in liver stiffness measured by MRE were associated with subsequent long-term improvements in patients with MASLD, suggesting that short-term MRE changes may provide insight into subsequent longer-term stiffness changes.

Background and Aim: Hypozincemia is common in patients with liver cirrhosis; however, its impact on prognosis and the prognostic cutoff remain unclear. This study aimed to identify a prognostic serum zinc threshold using data-driven methods and to evaluate the prognostic association of zinc supplementation with overall survival (OS). Methods: Among 721 zinc treatment-naive patients with liver cirrhosis, a prognostic serum zinc threshold associated with OS was determined. OS was subsequently compared between zinc-treated and untreated patients with baseline serum zinc below this threshold. Baseline characteristics were balanced between the zinc-treated and untreated groups (n = 119 each) using propensity score matching (PSM). Results: Analyses examining the association between serum zinc levels and prognosis demonstrated a dose-dependent relationship with OS. A serum zinc level of 70 µg/dL was identified as a prognostic cutoff strongly associated with OS. Among patients with serum zinc levels p = 0.034). The adjusted hazard ratio (95% confidence interval) for OS in the zinc-treated group compared with the untreated group was 0.64 (0.44–0.94). Conclusions: A prognostic serum zinc threshold was identified in patients with liver cirrhosis, and zinc supplementation was associated with improved survival. Routine monitoring and zinc supplementation to maintain levels above this reference value may contribute to better prognosis. However, due to the retrospective design and potential residual confounding, future prospective trials are required to validate these findings.

Background and Aims: Given the high prevalence of chronic liver diseases, non-invasive assessment of liver fibrosis is critical for screening and management of these conditions. While the FIB-4 index is widely used, its age-dependent nature may reduce specificity in older adults. The FIB-3 index, which excludes age, has been proposed as an alternative. This study aimed to compare the diagnostic performance of FIB-3 and FIB-4 for detecting advanced fibrosis across age groups using magnetic resonance elastography (MRE) as the reference standard. Methods: We retrospectively analyzed 3424 patients aged ≥30 years with chronic liver disease who underwent MRE. Advanced fibrosis was defined as liver stiffness ≥ 3.62 kPa. The cutoff values and diagnostic performance of the FIB-4 and FIB-3 indices for advanced fibrosis were evaluated within subgroups stratified by age quartiles (Q1–Q4), and the areas under the ROC curves (AUROCs) were compared using DeLong’s test. Results: Both FIB-3 and FIB-4 indices demonstrated comparable diagnostic accuracy for advanced fibrosis (AUROC 0.82 (95% CI: 0.81–0.83) for both; p = 0.70). In age-stratified analysis, the cutoff values for the FIB-4 index increased with increasing age (Q1: 1.72, Q2: 2.90, Q3: 3.66, Q4: 4.20), reflecting its age-dependent formula. In contrast, the FIB-3 index exhibited relatively minor variation in cutoff values across quartiles (Q1: 2.32, Q2: 3.52, Q3: 3.74, Q4: 3.14). Conclusions: FIB-3 index offers similar diagnostic accuracy to FIB-4 index while demonstrating more consistent performance across age groups. These findings provide evidence that FIB-3 index may be a useful alternative, particularly in older populations where FIB-4 index interpretation may be confounded by age.

Background and aims: The enhanced liver fibrosis (ELF) score is a blood test that combines three markers linked to liver fibrosis. The utility of the ELF score has been demonstrated primarily in Western countries, but whether it is useful in areas with a high number of elderly people suffering from chronic liver disease has yet to be determined. Methods: This is a prospective study that included 373 consecutive patients who underwent a liver biopsy and had their ELF score measured on the same day. The diagnostic accuracy of the ELF score for liver fibrosis and the effect of age on the ELF score were investigated. Results: The median (interquartile) ELF scores in F0, F1, F2, F3, and F4 are 8.7 (8.2–9.2), 9.3 (8.8–10.0), 10.1 (9.4–10.7), 10.7 (9.9–11.2), and 12.0 (11.2–12.7), respectively. ELF scores increased with increasing liver fibrosis stage (p < 0.001). The diagnostic accuracy of the ELF score and FIB-4 for significant fibrosis (F2–4) and advanced fibrosis (F3–4) was comparable, but the ELF score had a higher diagnostic accuracy for cirrhosis (F4) than FIB-4. When patients were stratified by age of 60 years, the median ELF score did not differ by age in F2, F3, and F4. However, the median FIB-4 increased in patients with ≥60 years compared to those with <60 years in all fibrosis stages. Conclusions: ELF score has high diagnostic accuracy for liver fibrosis, regardless of age, and it could be used as a primary screening method.

Background and Aim: Immune checkpoint inhibitors pose the risk of immune‐related adverse events (irAEs). Recent data suggest that irAEs may be associated with a favorable prognosis. This study aimed to investigate and analyze the association between these adverse events and the clinical benefits in patients with unresectable hepatocellular carcinoma.Methods: The study enrolled 130 patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab between November 2020 and January 2023 at a single center. The relationship between irAEs and both response rate and post‐treatment outcomes was investigated.Results: Out of the 130 patients, irAEs developed in 36 (27.7%) patients. The irAE group exhibited a significantly longer progression‐free survival (PFS) than the non‐irAE group, with a median PFS of 8.9 compared with 4.6 months (P < 0.01). No difference was found in the overall survival between the irAE and non‐irAE groups. The irAE group demonstrated significantly higher disease control rate (DCR) than the non‐irAE group (97.0% vs 65.5%, P < 0.01). The analysis by irAE severity revealed that the grade 1/2 group exhibited significantly longer PFS (7.9 vs 4.6 months, P = 0.007) and higher DCR (100% vs 65.5%, P < 0.01) than the non‐irAE group. Furthermore, hypothyroidism correlated with a favorable PFS (8.9 vs 5.4 months, P = 0.02), DCR (100% vs 71.3%, P = 0.03), and overall response rate (58.3% vs 18.5%, P = 0.005).Conclusion: The presence of irAEs is associated with prolonged PFS and higher DCR. Specifically, mild irAEs (grade 1/2) and hypothyroidism displayed prolonged PFS and higher DCR.

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.

Background Because of the global increase in the incidence of nonalcoholic fatty liver disease, the development of noninvasive, widely available, and highly accurate methods for assessing hepatic steatosis is necessary. Purpose To evaluate the performance of models with different combinations of quantitative US parameters for their ability to predict at least 5% steatosis in patients with chronic liver disease (CLD) as defined using MRI proton density fat fraction (PDFF). Materials and Methods Patients with CLD were enrolled in this prospective multicenter study between February 2020 and April 2021. Integrated backscatter coefficient (IBSC), signal-to-noise ratio (SNR), and US-guided attenuation parameter (UGAP) were measured in all participants. Participant MRI PDFF value was used to define at least 5% steatosis. Four models based on different combinations of US parameters were created: model 1 (UGAP alone), model 2 (UGAP with IBSC), model 3 (UGAP with SNR), and model 4 (UGAP with IBSC and SNR). Diagnostic performance of all models was assessed using area under the receiver operating characteristic curve (AUC). The model was internally validated using 1000 bootstrap samples. Results A total of 582 participants were included in this study (median age, 64 years; IQR, 52-72 years; 274 female participants). There were 364 participants in the steatosis group and 218 in the nonsteatosis group. The AUC values for steatosis diagnosis in models 1-4 were 0.92, 0.93, 0.95, and 0.96, respectively. The C-indexes of models adjusted by the bootstrap method were 0.92, 0.93, 0.95, and 0.96, respectively. Compared with other models, models 3 and 4 demonstrated improved discrimination of at least 5% steatosis (P < .01). Conclusion A model built using the quantitative US parameters UGAP, IBSC, and SNR could accurately discriminate at least 5% steatosis in patients with CLD. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Han in this issue.