Gifu Kyoritsu University

Accurate quantification of liver steatosis is critical for diagnosing steatotic liver disease. We aimed to evaluate a newly developed Steatosis Index (SI), which integrates multiple quantitative ultrasound (US) parameters, for assessing liver steatosis in patients with chronic liver disease (CLD). We retrospectively enrolled 568 patients with CLD who underwent both US attenuation coefficient (iATT) and MRI-proton density fat fraction (PDFF). With MRI-PDFF as a reference standard, we examined whether SI, developed by integrating backscatter coefficient and signal texture parameters into iATT, improves the accuracy of liver steatosis quantification and grading. SI demonstrated a stronger correlation (Pearson's r = 0.85 vs. 0.78, p < 0.001) and better concordance (Lin's concordance correlation coefficient = 0.84 vs. 0.75, p < 0.001), as well as higher area under the receiver operating characteristic curve for differentiating each steatosis grade: 0.94 vs. 0.92 for grade ≥ 1, 0.95 vs. 0.90 for grade ≥ 2, and 0.93 vs. 0.88 for grade 3, all p < 0.001), compared to iATT. It also showed significant improvement in reclassification and discrimination metrics, with internal validation using bootstrap resampling confirming the reliability of these findings. SI provided excellent diagnostic performance in quantifying and grading liver steatosis and may serve as a valuable tool for monitoring it in patients with CLD. Trial Registration UMIN Clinical Trials Registry, Number: UMIN000047411.

BackgroundFloodplains harbor highly biodiverse ecosystems, which have been strongly affected by both past climate change and by recent human activities, resulting in a high prevalence of many endangered species in these habitats. Understanding the history of floodplain species over a wide range of timescales can contribute to effective conservation planning. We reconstructed the population formation history of the Itasenpara bitterling Acheilognathus longipinnis, an endangered floodplain fish species in Japan, over a broad timescale based on phylogenetic analysis, demographic modeling, and historical demographic analysis using mitogenome and whole-genome sequences. A genome sequence was newly assembled as a reference for the resequencing analysis. This bitterling is distributed in three plains separated by high mountain ranges and exhibits ecological characteristics well adapted to floodplain environments.ResultsOur analyses revealed an unexpected population branching pattern, gene flow, and timing of the differentiation that occurred within a few hundred thousand years, i.e., long after the mountain uplift that was assumed to be the primary geological cause of the population differentiation. The analyses also showed that all local populations experienced a severe decline during the last glacial and post-glacial periods.ConclusionsOur results suggest that the floodplain bitterling was able to disperse through unknown routes after mountain uplift and that its populations were strongly influenced by climatic and geographic changes in glacial–interglacial cycles and subsequent human activities, probably related to its floodplain-dependent ecology. The genomic data highlight the unanticipated distribution process of this species and the magnitude of the impact of human activities, with important implications for its conservation.

We conducted a study using the Fibrosis-3 (FIB-3) index, which is the established age-independent index of fibrosis in nonviral liver disease and addresses the limitations of the FIB-4 index in older age group, to assess the liver fibrosis risk among diverse demographic groups in the general population. We analyzed 31 327 individuals who underwent health examinations between 2013 and 2020 and investigated the distribution of the FIB-3 index by age group. In addition, we examined the age distribution of the FIB-3 index stratified by background factors, such as sex, body mass index (BMI), alcohol consumption habits, and the presence or absence of fatty liver. In terms of age-specific distribution, the FIB-3 index remained below 1.5 in >90% of cases until the age of 50 years but exceeded 1.5 beyond the age of 50 years, in approximately 30% among those aged 70 years. Notably, the FIB-3 index above 31 years old was significantly higher in men than in women. Among the different BMI categories, individuals with BMI < 18.5 exhibited the highest prevalence of fibrosis. Habitual drinkers had a higher proportion with FIB-3. index ≥1.5, and some had FIB-3 index ≥2.5, raising the suspicion of advanced hepatic fibrosis. No distinct association was identified between the FIB-3 index and the presence of fatty liver. The FIB-3 index was useful for identifying cases of advancing hepatic fibrosis in a health checkup population. Liver fibrosis progresses with age in the general population, especially among men, those with low BMI, and habitual drinkers.

The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD. We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1 year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors. A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF ≥5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF >-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa). Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa).

Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival. To evaluate the impact of HCV treatment on such disparities. In a retrospective cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia. The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001). DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.

Background/Aim: The present study aimed to develop detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving Atezolizumab plus Bevacizumab (Atez/Bev). Methods: Between September 2020 and January 2023, the patients treated with Atez/Bev were enrolled (n=719, males 577, median age 74 years). Factors involved in overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were examined retrospectively, and the prognostic ability of the newly system was compared to CRAFITY score using concordance index (c-index) and Akaike Information Criterion (AIC) results. Results: Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used for IMnunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring. For IMABALI-De scores of 0/1/2/3/4/5, OS was not applicable (NA)/NA/26.11/18.79/14.07/8.32 months (P&lt;0.001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0/1/2, OS was 26.11/20.29/11.32 months (p&lt;0.001; AIC 2864.54, c-index 0.606). PFS for those IMABALI-De scores was 21.75/12.89/9.18/8.0/5.0/3.75 months (P&lt;0.001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores was10.32/7.68/3.57 months (p&lt;0.001; AIC 5246.61, c-index 0.574). IMABALI-De score had better AIC and c-index results as compared to CRAFITY score for both OS and PFS. Conclusion: The proposed IMABALI-De score may have a favorable prognostic predictive ability for uHCC patients with Atez/Bev.