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Concordance between metabolic dysfunction‐associated steatotic liver disease and nonalcoholic fatty liver disease
The concordance rate between nonalcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease in Japanese patients was 96.7% using the original waist circumference criteria and 96.2% using the Japanese metabolic syndrome criteria. Therefore, NAFLD could be considered MASLD using the original MASLD criteria, and insights from NAFLD research could be applied to MASLD.
Abstract
Aim
A multisociety consensus group proposed a new nomenclature for metabolic dysfunction-associated steatotic liver disease (MASLD). Although patients with nonalcoholic fatty liver disease (NAFLD) are expected to be reclassified as patients with MASLD under the new nomenclature, the concordance between MASLD and NAFLD remains unclear. Moreover, waist circumference could be adjusted by ethnicity for diagnosing MASLD; however, there are limited data on the optimal waist circumference in the Japanese population.
Methods
This cross-sectional study was conducted on 3709 Japanese patients with NAFLD. The primary endpoint was the prevalence of MASLD in patients with NAFLD. The difference between the original waist circumference criteria (>94 cm for men and >80 cm for women) and the Japanese metabolic syndrome criteria (≥85 cm for men and ≥90 cm for women) for concordance between NAFLD and MASLD was also investigated.
Results
According to the original criteria, the prevalence of MASLD in patients with NAFLD was 96.7%. Similarly, according to the Japanese waist circumference criteria, 96.2% of patients with NAFLD could be reclassified as those with MASLD. The concordance rate was significantly higher in the original criteria than in the Japanese criteria (p = 0.02).
Conclusions
NAFLD could be considered MASLD using the original MASLD criteria in the Japanese population, and insights from NAFLD research could be applied to MASLD.
Evidence of additive genetic variation for major milk proteins in dairy cows: A meta‐analysis
Abstract
In the past, there have been reports of genetic parameters for milk proteins in various dairy cattle populations. The high variability among genetic parameter estimates has been caused by this. This study aimed to use a random-effects meta-analysis model to compile published estimates of genetic parameter for major milk proteins of α-lactalbumin, β-lactoglobulin, sum of whey proteins, casein, αs1-casein, αs2-casein, β-casein, and κ-casein in dairy cows. The study used a total of 140 heritability and 256 genetic correlation estimates from 23 papers published between 2004 and 2022. The estimated range of milk protein heritability is from 0.284 (for α-lactalbumin in milk) to 0.596 (for sum of whey proteins). The genetic correlation estimates between casein and milk yield, milk fat and protein percentages were −0.461, 0.693, and 0.976, respectively (p < 0.05). The genetic correlation estimates between milk proteins expressed as a percentage of milk were significant and varied from 0.177 (between β-lactoglobulin and κ-casein) to 0.892 (between αs1-casein and αs2-casein). Moderate-to-high heritability estimates for milk proteins and their low genetic associations with milk yield and composition indicated the possibility for improving milk proteins in a genetic selection plan with negligible correlated effects on production traits in dairy cows.
Pro-inflammatory cytokines in spondyloarthritis: a case-control study
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Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease
The analysis of peripheral memory T lymphocyte frequencies can noninvasively sensitively detect nonalcoholic fatty liver disease (NAFLD) severity in addition to existing biomarkers. We should focus on CD8+ terminally differentiated effector memory T cells as a predictor of severe fibrosis and also on CD8+ effector memory T cells, and CD4+ and Th17 central memory T cells as indicators of the pathological progression of NAFLD.
Abstract
Aim
Differential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers.
Methods
We assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7+ CD45RA+ naïve T, CCR7+ CD45RA– central memory T cells (TCM), CCR7– CD45RA– effector memory T, and CCR7– CD45RA+ terminally differentiated effector memory T (TEMRA) cells in CD4+ and CD8+ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS).
Results
Several significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8+ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4+ TCM: lobular inflammation, and CD8+ TEMRA and effector memory T cells: hepatocellular ballooning).
Conclusions
Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD.
Modelling the lactation curve in Alpine × Beetal crossbred dairy goats using random regression models fitted with Legendre polynomial and B‐spline functions
Abstract
The current study sought to genetically assess the lactation curve of Alpine × Beetal crossbred goats through the application of random regression models (RRM). The objective was to estimate genetic parameters of the first lactation test-day milk yield (TDMY) for devising a practical breeding strategy within the nucleus breeding programme. In order to model variations in lactation curves, 25,998 TDMY records were used in this study. For the purpose of estimating genetic parameters, orthogonal Legendre polynomials (LEG) and B-splines (BS) were examined in order to generate suitable and parsimonious models. A single-trait RRM technique was used for the analysis. The average first lactation TDMY was 1.22 ± 0.03 kg and peak yield (1.35 ± 0.02 kg) was achieved around the 7th test day (TD). The present investigation has demonstrated the superiority of the B-spline model for the genetic evaluation of Alpine × Beetal dairy goats. The optimal random regression model was identified as a quadratic B-spline function, characterized by six knots to represent the central trend. This model effectively captured the patterns of additive genetic influences, animal-specific permanent environmental effects (c2) and 22 distinct classes of (heterogeneous) residual variance. Additive variances and heritability (h2) estimates were lower in the early lactation, however, moderate across most parts of the lactation studied, ranging from 0.09 ± 0.04 to 0.33 ± 0.06. The moderate heritability estimates indicate the potential for selection using favourable combinations of test days throughout the lactation period. It was also observed that a high proportion of total variance was attributed to the animal's permanent environment. Positive genetic correlations were observed for adjacent TDMY values, while the correlations became less pronounced for more distant TDMY values. Considering better fitting of the lactation curve, the use of B-spline functions for genetic evaluation of Alpine × Beetal goats using RRM is recommended.
Prognostic significance of C‐reactive protein in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab
CRP levels ≥1 mg/dL were associated with higher baseline ALBI score and AFP levels, lower disease control rate, and shorter overall survival in patients (n = 213) who received atezolizumab plus bevacizumab for advanced HCC. This study highlighted the importance of considering the treatment line when evaluating CRP as a prognostic factor.
Abstract
Aim
C-reactive protein (CRP) is both an inflammatory and prognostic marker in various cancers. This study aimed to elucidate the characteristics of CRP and the prognostic factors in patients who were administered with atezolizumab plus bevacizumab (ATZ + BEV) for unresectable hepatocellular carcinoma (HCC).
Methods
A total of 213 patients who received ATZ + BEV for HCC from November 2020 to March 2023 at 15 hospitals were enrolled in this retrospective study. The prognosis was analyzed by subdividing the patients based on baseline characteristics, radiologic response, and treatment lines. Accuracy of survival prediction was assessed using CRP, alpha fetoprotein (AFP), C-reactive protein and alpha fetoprotein in immunotherapy (CRAFITY), and Glasgow Prognostic Score.
Results
Compared with patients with baseline CRP <1 mg/dL, those with baseline CRP ≥1 mg/dL (n = 45) had a significantly higher baseline albumin–bilirubin score and AFP levels, significantly lower disease control rate (62.2%), and significantly shorter median overall survival (hazards ratios 2.292; 95% confidence interval 1.313–5.107; log-rank test, p < 0.001). Multivariate analysis identified CRP ≥1 mg/dL, AFP ≥100 ng/mL, and modified albumin–bilirubin grade as the significant prognostic factors. The baseline CRP, AFP, CRAFITY, and Glasgow Prognostic Score demonstrated higher discrimination for 1-year survival prediction after first-line ATZ + BEV administration, compared with beyond second line, with area under the receiver operating characteristic curves of 0.759, 0.761, 0.805, and 0.717, respectively.
Conclusions
CRP was a significant biomarker in patients treated with ATZ + BEV for HCC. Elevated CRP levels may indicate aggressive cancer progression and potential resistance to ATZ + BEV therapy.
Secukinumab for children and adolescents with enthesitis-related arthritis and psoriatic arthritis: lessons from treatment in adults and the way forward
The role of immune reconstitution in relapse after allogeneic hematopoietic stem cell transplantation
The change in Fibrosis‐4 index in Japanese patients with type 2 diabetes treated by a fixed‐ratio combination therapy of insulin degludec and liraglutide: A retrospective observational study
The efficacy of a combination preparation of insulin degludec and liraglutide in patients with type 2 diabetes, focusing particularly on the change in the FIB-4, was investigated. Fixed-ratio combination therapy using insulin degludec and liraglutide is useful for liver protection, improving blood glucose levels, and preventing an increase in bodyweight.
Abstract
Aim
The efficacy of titratable fixed-ratio combination therapy by a combination preparation of insulin degludec and liraglutide (IDegLira) in Japanese patients with type 2 diabetes, focusing particularly on the change in Fibrosis-4 index (FIB-4), a noninvasive method for the evaluation of liver fibrosis, was investigated.
Methods
As the full analysis set, 113 patients were treated with IDegLira. The patients were categorized into two groups according to the absence (GLP-1RA-naïve group, n = 72) or presence (GLP-1RA-treated group, n = 41) of glucagon-like peptide-1 receptor agonist (GLP-1RA) use before starting IDegLira. The clinical parameters were retrospectively determined over 6 months.
Results
The glycated hemoglobin value was significantly reduced in both groups. The bodyweight significantly decreased from 67.4 ± 11.0 kg at baseline to 66.4 ± 11.6 kg at 6 months in the GLP-1RA-naïve group, although it slightly increased in the GLP-1RA-treated group. FIB-4 significantly decreased from 1.60 ± 0.84 at baseline to 1.49 ± 0.74 at 6 months in the GLP-1RA-naïve group. Although FIB-4 significantly increased in the GLP-1RA-treated group, it remained within the low-risk level for liver fibrosis.
Conclusion
Fixed-ratio combination therapy using IDegLira for the treatment of type 2 diabetes is useful for glycemic control and weight management. In particular, IDegLira may be more effective for lowering FIB-4 than adding unused oral antidiabetic agents or increasing the dose of insulin in GLP-1RA-naïve patients.