Aim
Metabolic associated fatty liver disease (MAFLD) partly overlaps with non‐alcoholic fatty liver disease (NAFLD). Thus, using a generalized estimating equation (GEE) approach, we aimed to ...investigate the difference in worsening of atherosclerotic cardiovascular disease (ASCVD) risk between patients with MAFLD and NAFLD. We also investigated factors related to the difference between the two groups.
Methods
We enrolled 2306 subjects with fatty liver (MAFLD 80.7%, NAFLD 63.4%). Subjects with MAFLD/NAFLD were sub‐classified into three groups: NAFLD with no metabolic dysfunction (non‐Met NAFLD), overlapping, and MAFLD with moderate alcohol consumption (mod‐Alc MAFLD). ASCVD risk was estimated by non‐invasive tests, including the Suita score. An event was defined as worsening of these scores from the low‐risk to the high‐risk group. Independent factors for the event were analyzed by Cox regression analysis with the GEE.
Results
In Cox regression analysis, MAFLD (HR 1.08, 95% CI 1.02–1.15, p = 0.014) and alcohol consumption (20–39 g/day; HR 1.73, 95% CI 1.26–2.36, p = 0.001) were independently associated with worsening of the Suita score. In a subanalysis, the incidence of the event was significantly lower in non‐Met NAFLD than in the overlapping group (HR 0.70, 95% CI 0.50–0.98, p = 0.042). However, no significant difference was observed in the incidence between the overlapping and mod‐Alc MAFLD group (HR 1.19, 95% CI 0.89–1.58, p = 0.235).
Conclusions
The GEE approach demonstrates that MAFLD better identifies patients with worsening of ASCVD risk than NAFLD. Moreover, the superiority of MAFLD over NAFLD was due to the presence of metabolic dysfunction rather than moderate alcohol consumption.
Background
Few studies have evaluated both liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD) using both FibroScan
®
M and XL probes. This study was performed to ...investigate the accuracy of both FibroScan
®
probes to diagnose liver fibrosis and steatosis in patients with NAFLD.
Methods
We prospectively enrolled 137 consecutive patients with clinically suspected NAFLD in our joint-research facilities. Liver biopsies, liver stiffness measurements (LSMs), and controlled attenuation parameter (CAP) measurements were performed, and 122 patients with NAFLD diagnosed pathologically by central pathologists were included in the final analysis.
Results
Reliable LSM results were obtained in 85.2% (M) and 89.3% (XL) of patients, and CAP was reliable in 90.2% (M) and 90.2% (XL). The median LSM was significantly lower with the XL than M probe, and CAP was significantly higher with the XL than M probe. The optimal cut-off values for diagnosing the fibrosis stage were lower for LSM with the XL than M probe (stage ≥ 2, 6.7 vs. 7.0; stage ≥ 3, 8.2 vs. 10.8; stage 4, 14.3 vs. 16.8, respectively), whereas those of CAP were higher for the XL than M probe (score of ≥ 2, 273 vs. 267; score of 3, 302 vs. 286, respectively). There were no significant differences in accuracy of the LSM and CAP between the probes.
Conclusions
Liver fibrosis and steatosis could be equally evaluated with FibroScan
®
M and XL probes in patients with NAFLD. There was no significant difference in diagnostic accuracy between the two probes using probe-specific cut-off values.
This retrospective cohort study explored the prevalence of substantial weight loss (≥10% per year) in independent older individuals in order to develop and validate a scoring system for high-risk ...group identification and targeted intervention against malnutrition. We used insurance claims and the Kokuho Database (KDB), a nationwide repository of Japanese-specific health checkups and health assessments for the older people. The study included 12,882 community-dwelling individuals aged 75 years and older who were self-supported in their activities of daily living in Saga Prefecture, Japan. Health evaluations and questionnaires categorized weight-loss factors into organic, physiological, psychological, and non-medical domains. The resulting scoring system (SAGA score), incorporating logistic regression models, predicted ≥ 10% annual weight-loss risk. The results revealed a 1.7% rate of annual substantial weight loss, with the SAGA score effectively stratifying the participants into low-, intermediate-, and high-risk categories. The high-risk category exhibited a weight-loss rate of 17.6%, highlighting the utility of this scoring system for targeted prevention. In conclusion, the validated SAGA score is a crucial tool for identifying individuals at high risk of significant weight loss, enabling tailored interventions and social support benefiting both older individuals and their relatives.This retrospective cohort study explored the prevalence of substantial weight loss (≥10% per year) in independent older individuals in order to develop and validate a scoring system for high-risk group identification and targeted intervention against malnutrition. We used insurance claims and the Kokuho Database (KDB), a nationwide repository of Japanese-specific health checkups and health assessments for the older people. The study included 12,882 community-dwelling individuals aged 75 years and older who were self-supported in their activities of daily living in Saga Prefecture, Japan. Health evaluations and questionnaires categorized weight-loss factors into organic, physiological, psychological, and non-medical domains. The resulting scoring system (SAGA score), incorporating logistic regression models, predicted ≥ 10% annual weight-loss risk. The results revealed a 1.7% rate of annual substantial weight loss, with the SAGA score effectively stratifying the participants into low-, intermediate-, and high-risk categories. The high-risk category exhibited a weight-loss rate of 17.6%, highlighting the utility of this scoring system for targeted prevention. In conclusion, the validated SAGA score is a crucial tool for identifying individuals at high risk of significant weight loss, enabling tailored interventions and social support benefiting both older individuals and their relatives.
Background
Liver cirrhosis induces marked metabolic disorders, protein-energy malnutrition, and sarcopenia. The objective of the study reported here was to investigate the effects of dietary ...branched-chain amino acids (BCAAs) on systemic glucose metabolism, skeletal muscle, and prognosis of patients with liver cirrhosis.
Methods
Japanese patients with liver cirrhosis (
n
= 21) were enrolled into a longitudinal study in which their diets were supplemented with BCAAs. We evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI) and intramuscular adipose tissue content (IMAC) using computed tomography.
Results
After 48 weeks of supplementation with BCAAs, there were no changes in glucose metabolism and skeletal muscle findings. In patients with ameliorated hypoalbuminemia, IMAC was significantly decreased and SAI was preserved concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels (
P
< 0.01 each). In patients without increased albumin levels, IMAC was significantly increased and the SAI was significantly decreased (
P
< 0.01 each). Liver-related event-free survival rates for 72 months were 63.6% in patients with decreased IMAC and 20.0% in patients with increased IMAC.
Conclusions
Amelioration of hypoalbuminemia associated with BCAA supplementation correlated with decreased fat accumulation in skeletal muscle, maintenance of skeletal muscle mass, and improved glucose sensitivity, all factors which may contribute to improving the survival of patients with liver cirrhosis.
Aim
Advanced hepatic fibrosis is seen in individuals with potential hepatocellular carcinoma and cardiovascular disease. Hepatic fibrosis can be assessed using a combination of the FIB‐4 index and ...imaging modalities, including shear wave elastography. We aimed to investigate the prevalence of advanced fibrosis in the general population and the profiles associated with advanced fibrosis using a data‐mining analysis.
Methods
We enrolled 1155 health checkup examinees (median age 53 years, 685 women, 470 male). Advanced fibrosis was defined by FIB‐4 index ≥1.3 and liver stiffness ≥8.07 kPa using shear wave elastography. Participants were classified as normal‐mild fibrosis (n = 1035) or advanced fibrosis (n = 120). Factors associated with advanced fibrosis were analyzed by logistic regression and decision‐tree analyses.
Results
Advanced fibrosis was observed in 10.4% of participants (120/1155). In the logistic regression analysis, independent factors for advanced fibrosis were age (≥75 years; OR 2.12, 95% CI 1.021–4.415; P = 0.0419) and the presence of metabolic syndrome (OR 2.51, 95% CI 1.416–4.462; P = 0.0017). The decision‐tree analysis showed two profiles associated with advanced fibrosis: profile 1 – individuals aged ≥65 years with metabolic syndrome and mild‐to‐moderate alcohol consumption (prevalence of advanced fibrosis 73.3%); and profile 2 – individuals without metabolic syndrome, aged ≥75 years, with no exercise habit (prevalence of advanced fibrosis 56.3%).
Conclusions
Advanced fibrosis was observed in 10.4% of health checkup examinees. Furthermore, we showed that aging, metabolic syndrome with mild‐to‐moderate alcohol consumption, and physical inactivity were associated with advanced fibrosis. Thus, prevention of metabolic syndrome and alcohol withdrawal, as well as exercise habits, might inhibit the progression of hepatic fibrosis.
Background and Aim
Sarcopenia, initially proposed as decreased of muscle mass and strength, is associated with aging and malignant diseases. The aim of the present study was to determine whether ...there is a correlation between sarcopenia and the recurrence of hepatocellular carcinoma (HCC) after curative treatment.
Methods
We conducted a retrospective analysis of consecutive naive patients with HCC who underwent curative resection or radiofrequency ablation. To eliminate the influence of cause or the severity of liver damage, subjects were limited to those with HCC with hepatitis C‐related cirrhosis and Child–Pugh class A liver function. Patients were assessed using computed tomographic measurement of muscle mass at the level of the third lumbar (L3) vertebrae, the L3 skeletal muscle index (L3 SMI). Sarcopenia was defined by using previously published, sex‐specific cut‐off value.
Results
Sarcopenia was present in 61 of 92 patients. Patients’ median age was 71.5 years (range, 47–84), and the baseline characteristics of patients were comparable between patients with and without sarcopenia except for sex, serum albumin level, prothrombin time, diabetes mellitus and body mass index. Recurrence rates at 1, 3 and 5 years were 39.1%,77.1%,81.7% for patients with sarcopenia and 23.5%,59.5% and 75.7% for patients without sarcopenia, respectively (P = 0.03). Multivariate Cox analysis revealed that sarcopenia and preoperative α‐fetoprotein of more than 40 ng/mL were significant independent factors for recurrence.
Conclusion
Sarcopenia is a risk factor for recurrence in patients with HCC who were treated with curative treatment.
Epidemiological evidence suggests that there is a link between diabetes and mood disorders, such as depression and anxiety. Although peripheral or central inflammation may explain this link, the ...molecular mechanisms are not fully understood and few effective treatments for diabetes or mood disorders are available. In the present study, we aimed to determine whether transforming growth factor (TGF)-β2, an anti-inflammatory substance, might represent a potential therapeutic agent for diabetes-related mood behaviors. TGF-β2 expression in the hippocampus is affected by anxiolytic drugs and stress exposure, it is able to cross the blood-brain barrier, and it is as an exercise-induced physiological adipokine that regulates glucose homeostasis. Therefore, we hypothesized that a chronic TGF-β2 infusion would ameliorate diabetes-related glucose intolerance and mood dysregulation. To determine the effects of the chronic administration of TGF-β2 on diabetes, we implanted osmotic pumps containing TGF-β2 into type 2 diabetic mice (
db/db
mice), and age-matched non-diabetic control wild type mice and
db/db
mice were infused with vehicle (PBS), for 12 consecutive days. To assess anxiety-like behaviors and glucose homeostasis, the mice underwent elevated plus maze testing and intraperitoneal glucose tolerance testing. Hippocampal and perigonadal visceral white adipose tissue perigonadal white adipose tissue samples were obtained 12 days later. Contrary to our hypothesis, TGF-β2 infusion had no effect on diabetes-related glucose intolerance or diabetes-related behavioral defects, such as inactivity. In
db/db
mice, the expression of inflammatory markers was high in pgWAT, but not in the hippocampus, and the former was ameliorated by TGF-β2 infusion. The expression of brain-derived neurotrophic factor and neuronal nitric oxide synthase, important regulators of anxiety-like behaviors, was low in
db/db
mice, but TGF-β2 infusion did not affect their expression. We conclude that although TGF-β2 reduces the expression of pro-inflammatory markers in the adipose tissue of diabetic mice, it does not ameliorate their obesity or mood dysregulation.
Background
To present the strategies and preliminary findings of the first 3 years after implementing a
Helicobacter pylori
screening and eradication program to prevent gastric cancer in Saga ...Prefecture.
Methods
A screening and treatment program to eradicate
H. pylori
from third-grade junior high students was started in Saga Prefecture in 2016, using local governmental grants. Screening was with urinary anti-
H. pylori
antibody tests, followed by
H. pylori
stool antigen tests for students who were antibody positive. Those positive on both tests underwent
H. pylori
eradication by triple therapy based on a potassium-competitive acid blocker.
Results
From 2016 to 2018, the participation rate was 83.1% and the
H. pylori
infection rate was 3.1% (660/21,042). The participation rates were higher in 2017 (85.4%) and 2018 (85.9%) compared with 2016 (78.5%) (
P
< 0.0001), and the infection rate also decreased in a time-dependent manner (2016: 3.6%, 2017: 3.3%, 2018: 2.5%,
P
= 0.0001). In total, 501 students positive for
H. pylori
received eradication therapy (85.1% success) and adverse events occurred in 20 of these (4.0%). However, no serious complications occurred.
Conclusions
The
H. pylori
screening and eradication project for school students in Saga Prefecture has started successfully and we have seen both a steady increase in the participation rate and a steady decrease in the infection rate, without major safety concerns.
Tyrosine kinase 2 (TYK2), a member of the JAK family, has attracted attention as a potential therapeutic target for autoimmune diseases. However, the role of TYK2 in CD8
T cells and autoimmune type 1 ...diabetes (T1D) is poorly understood. In this study, we generate Tyk2 gene knockout non-obese diabetes (NOD) mice and demonstrate that the loss of Tyk2 inhibits the development of autoreactive CD8
T-BET
cytotoxic T lymphocytes (CTLs) by impairing IL-12 signaling in CD8
T cells and the CD8
resident dendritic cell-driven cross-priming of CTLs in the pancreatic lymph node (PLN). Tyk2-deficient CTLs display reduced cytotoxicity. Increased inflammatory responses in β-cells with aging are dampened by Tyk2 deficiency. Furthermore, treatment with BMS-986165, a selective TYK2 inhibitor, inhibits the expansion of T-BET
CTLs, inflammation in β-cells and the onset of autoimmune T1D in NOD mice. Thus, our study reveals the diverse roles of TYK2 in driving the pathogenesis of T1D.
Exercise training ameliorates nonalcoholic fatty liver disease (NAFLD) as well as obesity and metabolic syndrome. Although it is difficult to eliminate the effects of body weight reduction and ...increased energy expenditure-some pleiotropic effects of exercise training-a number of studies involving either aerobic exercise training or resistance training programs showed ameliorations in NAFLD that are independent of the improvements in obesity and insulin resistance.
studies have identified effects of exercise training on the liver, which may help to explain the "direct" or "independent" effect of exercise training on NAFLD. Exercise training increases peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression, improves mitochondrial function and leads to reduced hepatic steatosis, inflammation, fibrosis, and tumor genesis. Crosstalk between the liver and adipose tissue, skeletal muscle and the microbiome is also a possible mechanism for the effect of exercise training on NAFLD. Although numerous studies have reported benefits of exercise training on NAFLD, the optimal duration and intensity of exercise for the prevention or treatment of NAFLD have not been established. Maintaining adherence of patients with NAFLD to exercise training regimes is another issue to be resolved. The use of comprehensive analytical approaches to identify biomarkers such as hepatokines that specifically reflect the effect of exercise training on liver functions might help to monitor the effect of exercise on NAFLD, and thereby improve adherence of these patients to exercise training. Exercise training is a robust approach for alleviating the pathogenesis of NAFLD, although further clinical and experimental studies are required.
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