Masayuki Kurosaki

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.

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).

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease, and strategies to prevent NAFLD-related hepatocellular carcinoma and liver failure are of increasing importance. Recently, the classification of steatotic liver disease (SLD) has been redefined based on alcohol intake: metabolic dysfunction-associated SLD (MASLD, mild alcohol intake), MASLD and increased alcohol intake (MetALD, moderate alcohol intake), and alcohol-related liver disease (ALD, heavy alcohol intake). Because the concordance rate between NAFLD and MASLD is 96–99%, MASLD can be regarded as clinically equivalent to NAFLD. When the risk of liver-related events is compared across these categories, ALD carries the highest risk, followed by MetALD and then MASLD. In contrast, the risk of cardiovascular events is highest in MASLD, followed by MetALD and ALD. All three subtypes also confer an increased risk of extrahepatic malignancies. Within MASLD, a distinct lean phenotype (lean MASLD) exists; compared with overweight MASLD, lean MASLD has a lower cardiovascular risk, but a higher risk of liver-related events. These findings highlight that complication risks differ among MASLD, MetALD, and ALD, necessitating phenotype-specific surveillance strategies. Although no pharmacotherapies for MASLD are currently approved in Japan, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors have been reported to improve histological inflammation and fibrosis in patients with MASLD, and their approval for MASLD is anticipated. Similarly, statins and pemafibrate have shown improvements in liver function and steatosis in patients with dyslipidaemia and are already used in routine clinical practice for comorbid cases.

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: In the hepatitis B e antigen positive (HBeAg+) chronic infection disease phase, approved treatments have limited effects on hepatitis B surface antigen (HBsAg) and HBeAg. Objective: The phase 2 REEF-IT study ( NCT04439539 ) assessed safety, efficacy and pharmacokinetics of pegylated interferon-α2a (PegIFN-α2a) add-on to JNJ-73763989 (JNJ-3989)±bersacapavir+nucleos(t)ide analogues (NA) in not currently treated, HBeAg+chronic hepatitis B. Design: Participants received JNJ-3989 (200 mg every 4 weeks)+NA±bersacapavir (250 mg daily) for 36–52 weeks (induction) followed by 12 weeks of PegIFN-α2a (180 µg weekly) add-on. The primary endpoint was the proportion of participants with HBsAg seroclearance 24 weeks after stopping all treatment including NA. Changes in viral markers, safety and pharmacokinetics were assessed. Results: 49/54 (91%) enrolled participants completed the study; 52% were male, with mean age of 33.6 years. No participant achieved the primary endpoint; one met NA completion criteria. 11/54 (20.4%) participants achieved HBsAg seroclearance at least once, 6 of them maintained it until Follow-up Week 48 (FUW48). Overall mean (SE) change from baseline in HBsAg of –2.85 (0.13), –3.61 (0.18) and –2.63 (0.26)log ₁₀ IU/mL were observed at end of induction, end of treatment and FUW48. 16/53 (30.2%) participants reached HBeAg seroclearance at least once; 12 maintained it until FUW48. Similar proportions of participants experienced an adverse event (AE) during induction (83.3%), PegIFN-α2a add-on (85.7%) and follow-up (64.7%). There were no deaths or serious AEs; two participants discontinued PegIFN-α2a. Conclusions: In this population, adding PegIFN-α2a increased HBsAg declines after reductions by JNJ-3989; 20.4% achieved HBsAg seroclearance at least once. Treatment was generally safe with acceptable tolerability. Trial registration number: NCT04439539 .

Background and aim: The incidence of hepatocellular carcinoma (HCC) is positively correlated with age, and the population of patients with HCC was also older at the time of clinical diagnosis. In the SURF trial, elderly people aged ≥80 years were excluded. We aimed to study the efficacy and safety of radiofrequency ablation (RFA) for patients aged over 80 years. Methods: Patients who underwent RFA at our institution for the initial treatment of HCC tumors with largest diameters of ≤3 cm, and ≤3 HCC nodules from January 2011 to December 2023. Treatment outcomes and prognoses were examined in the elderly group (≥80 years) and in the nonelderly group (<80 years). The Cox proportional hazards model was used to determine the factors associated with treatment outcomes and prognoses. Results: Of the 518 eligible patients, 136 patients were aged ≥80 years. The median overall survival (OS) values were 80 (95%CI; 60–96) and 123 (95%CI; 101–nucleotide analogs (NA)) months (p = 0.021) in the elderly and nonelderly groups, respectively. For liver disease-related deaths, the median OS values were 97 (95% CI; 80–NA) and NR (95% CI; NA–NA) months (p = 0.62) in the elderly and nonelderly groups, respectively. In the multivariate analysis, factors associated with OS were ALBI grade 2 or 3 (HR, 1.67, 95%CI; 1.07–2.60), DCP ≥ 40 mAU/ml (HR, 2.08, 95%CI; 1.42–3.04), persistent hepatitis C virus (HCV) infection (HR, 5.46, 95%CI; 3.08–9.69), and nonviral liver disease (HR, 4.19, 95%CI; 2.32–7.57). The median recurrence-free survival values were 16 (95%CI; 14–22) and 26 (95%CI; 19–30) months, respectively (p = 0.023). HCC recurrence was significantly associated with the male sex (HR, 1.50, 95%CI; 1.17–1.93), elderly group (HR, 1.37, 95%CI; 1.10–1.95), ALBI grade 2 or 3 (HR, 1.39, 95%CI; 1.07–1.80), DCP ≥ 40 mAU/ml (HR, 1.41, 95%CI; 1.10–1.81), and persistent HCV infection (HR, 1.67, 95%CI; 1.30–2.15). The factors associated with liver disease-related death were ALBI grade 2 or 3 (HR, 2.17, 95% CI; 1.26–3.75), DCP ≥ 40 mAU/ml (HR, 2.33, 95% CI; 1.47–3.69), and persistent HCV infection (HR, 2.22, 95% CI; 1.39–3.56). Conclusions: In RFA for tumors with diameters of ≤3 cm and ≤3 HCC nodules, age over ≥80 years was not a significant factor associated with OS or liver disease-related death. The results support that RFA would be a promising treatment option for patients with HCC patients aged ≥80 years.