Sufficient attention has not been given to machine learning (ML) models using longitudinal data for investigating important predictors of new onset of hypertension. We investigated the predictive ability of several ML models for the development of hypertension.

A total of 15 965 Japanese participants (men/women: 9,466/6,499, mean age: 45 years) who received annual health examinations were randomly divided into a training group (70%, n = 11,175) and a test group (30%, n = 4,790). The predictive abilities of 58 candidates including fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, were investigated by statistics analogous to the area under the curve (AUC) in receiver operating characteristic curve analyses using ML models including logistic regression, random forest, naïve Bayes, extreme gradient boosting and artificial neural network.

During a 10-year period (mean period: 6.1 years), 2,132 subjects (19.1%) in the training group and 917 subjects (19.1%) in the test group had new onset of hypertension. Among the 58 parameters, systolic blood pressure, age and FLI were identified as important candidates by random forest feature selection with 10-fold cross-validation. The AUCs of ML models were 0.765-0.825, and discriminatory capacity was significantly improved in the artificial neural network model compared to that in the logistic regression model.

The development of hypertension can be simply and accurately predicted by each ML model using systolic blood pressure, age and FLI as selected features. By building multiple ML models, more practical prediction might be possible.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes without significant alcohol consumption. It is closely associated with sedentarism, hypercaloric diets, obesity, dyslipidemia, insulin resistance, type 2 diabetes mellitus, and genetic predisposition. NAFLD comprises a spectrum of liver disorders, from simple steatosis to non-alcoholic (NASH) and liver cirrhosis. The complex etiological mechanisms include oxidative stress, inflammation, apoptosis, and fibrosis; therefore, its management is challenging. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i), a class of antidiabetic drugs, have emerged as promising therapeutic agents due to their ability to improve key metabolic parameters, including obesity, dyslipidemia, insulin resistance, and hyperglycemia. This review explores the cellular mechanisms by which SGLT2i, either as monotherapy or combined with other treatments, modulate signaling pathways involved in lipid and carbohydrate metabolism. Additionally, we examine their effects on oxidative stress, inflammation, fibrosis, and apoptosis, which are critical drivers of NAFLD progression. This review is intended to summarize the multiple benefits of SGLT2 inhibitors and to educate healthcare providers on the therapeutic potential of these drugs in order to foster their incorporation into effective NAFLD management plans.

Dysregulated programmed cell death pathways mechanistically contribute to hepatic inflammation and fibrogenesis in non-alcoholic steatohepatitis (NASH). Identification of cell death genes may offer insights into diagnostic and therapeutic strategies for NASH.

Data from multiple NASH cohorts were integrated, and 12 machine learning algorithms were applied to identify key dysregulated cell death-related genes and develop a binary classification model for NASH. Spearman's rank correlation coefficients quantified associations between these genes and clinical markers, immune infiltration profiles, and signature genes encoding pro-inflammatory mediators, metabolic regulators, and fibrotic drivers. Gene set enrichment analysis (GSEA) was performed to delineate the mechanistic underpinnings of these key genes. Consensus clustering analysis was then used to stratify patients with NASH into distinct phenotypic subgroups based on expression levels of these genes.

A NASH prediction model, developed using the random forest (RF) algorithm, demonstrated high diagnostic accuracy across multiple cohorts. Four key genes, enriched in lipid metabolism and inflammation pathways, were identified. Their transcriptional levels were significantly correlated with the non-alcoholic fatty liver disease activity score (NAS), hepatic inflammatory infiltration, molecular signatures of metabolic dysregulation (lipid homeostasis regulators), and fibrosis progression. These genes also enabled accurate classification of patients with NASH into clusters reflecting varying disease severity.

A binary classification model, developed using the RF algorithm, accurately identified patients with NASH. The four cell death genes, identified through 12 machine learning algorithms, represent potential biomarkers and therapeutic targets for NASH. These genes contribute to inflammation-related immune cell activation, lipid metabolism dysregulation, and liver fibrosis, highlighting the complex interplay between cell death and NASH progression.

Objective: Our study aims to develop a personalized nomogram model for predicting the risk of nonalcoholic fatty liver disease (NAFLD) in hypertension (HTN) patients and further validate its effectiveness. Methods: A total of 1250 hypertensive (HTN) patients from Guangxi, China, were divided into a training group (875 patients, 70%) and a validation set (375 patients, 30%). LASSO regression, in combination with univariate and multivariate logistic regression analyses, was used to identify predictive factors associated with nonalcoholic fatty liver disease (NAFLD) in HTN patients within the training set. Subsequently, the performance of an NAFLD nomogram prediction model was evaluated in the separate validation group, including assessments of differentiation ability, calibration performance, and clinical applicability. This was carried out using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results: The risk-prediction model for the HTN patients concomitant with NAFLD included oral antidiabetic drugs (OADs) (OR = 2.553, 95% CI: 1.368-4.763), antihypertensives (AHs) (OR = 7.303, 95% CI: 4.168-12.794), body mass index (BMI) (OR = 1.145, 95% CI: 1.084-1.209), blood urea nitrogen (BUN) (OR = 0.924, 95% CI: 0.860-0.992), triglycerides (TGs) (OR = 1.474, 95% CI: 1.201-1.809), aspartate aminotransferase (AST) (OR = 1.061, 95% CI: 1.018-1.105), and AST/ALT ratio (AAR) (OR = 0.249, 95% CI: 0.121-0.514) as significant predictors. The AUC of the NAFLD risk-prediction model in the training set and the validation set were 0.816 (95% CI: 0.785-0.847) and 0.794 (95% CI: 0.746-0.842), respectively. The Hosmer-Lemeshow test showed that the model has a good goodness-of-fit (p-values were 0.612 and 0.221). DCA suggested the net benefit of using a nomogram to predict the risk of HTN patients concomitant with NAFLD is higher. These results suggested that the model showed moderate predictive ability and good calibration. Conclusions: BMI, OADs, AHs, BUN, TGs, AST, and AAR were independent influencing factors of HTN combined with NAFLD, and the risk prediction model constructed based on this could help to identify the high-risk group of HTN combined with NAFLD at an early stage and guide the development of interventions. Larger cohorts with multiethnic populations are essential to verify our findings.

Background/Objectives: We aim to determine if cytokeratin-18 fragment (CK-18F) could be used to diagnose metabolic dysfunction-associated steatohepatitis (MASH). Methods: A total of 289 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled in the analysis. To evaluate the association between CK-18F levels and the histological features of MASH, weighted receiver operating characteristic (ROC) curve analyses were performed. The diagnostic utility of CK-18F was compared with that of the Mac-2 binding protein glycan isomer (M2BPGi). Additionally, we assessed the predictive performance of combining CK-18F with either the FIB-4 index or the FIB-3 index for diagnosing MASH and investigated predictors of future progression to cirrhosis. Results: CK-18F was more useful for MASH diagnosis than M2BPGi and the FIB-4 index in the multivariate analysis, with a sensitivity of 47% and specificity of 80% at a CK-18F cutoff value of 750 U/L. Because CK-18F decreases with advanced liver fibrosis, the combination of the FIB-4 or FIB-3 index with CK-18F was examined to identify cases with cirrhosis. The combination of the CK-18F level and the FIB-3 index better predicted MASH than the combination of the CK-18F level and the FIB-4 index. The FIB-3 index was the most useful predictor of cirrhosis on imaging five years after diagnosis with F2 or less disease. Conclusions: CK-18F is useful for MASH diagnosis, and the diagnostic algorithm combining CK-18F with the FIB-3 index may be more useful than the previously reported MASH diagnostic algorithm that combined it with the FIB-4 index.

Psoriasis is associated with comorbidities like metabolic syndrome and nonalcoholic fatty liver disease, increasing the risk of liver fibrosis. This study evaluated the long-term effects of guselkumab on liver fibrosis in 154 psoriasis patients using the Fibrosis-4 (FIB-4) index, a noninvasive marker of fibrosis, over 3 years. Patients were stratified by baseline FIB-4 (≥ 1.3 or < 1.3) and age (35-65 years). Mean FIB-4 values remained stable across all subgroups, with no significant changes observed. High-risk patients (FIB-4 ≥ 1.3) showed minor, nonsignificant fluctuations, while low-risk patients (FIB-4 < 1.3) exhibited a mild, age-related upward trend. Disease duration emerged as a key factor influencing FIB-4, highlighting the importance of early treatment. These findings suggest guselkumab does not contribute to liver fibrosis progression in psoriasis patients. Further research with advanced methods like imaging or biopsy is needed to confirm the long-term hepatic safety of IL-23 inhibitors like guselkumab.

Objective Recent developments in ultrasound elastography (UE) and ultrasound attenuation imaging (UA) have enabled the detection of advanced liver fibrosis and steatosis in patients with steatotic liver disease (SLD), which is prevalent worldwide. In patients with SLD, the presence of advanced liver fibrosis determines the risk of hepatocarcinogenesis, and UE and UA are expected to play important roles in liver cancer surveillance. We conducted a questionnaire survey among medical facilities in Saga Prefecture regarding the actual status of awareness and implementation of UE and UA. Methods A 16-item questionnaire was sent to 275 facilities that employed members of the Liver Cancer Control Medical Association in Saga Prefecture. The response rate was 56% (153 facilities), and data from 142 facilities were analyzed after excluding 11 facilities. Results The most common facilities were outpatient clinics (60%) followed by hospitals with ≥100 beds (14%). In 48% of the facilities, an average of 10-49 abdominal ultrasound examinations were performed monthly. The rates of recognition that UE and UA are useful for fibrosis and steatosis were 65% (92/142) and 41% (58/142), respectively. The actual availability of UE and UA in facilities with ultrasound machines was 21% (30/142) and 12% (17/142), respectively; UE and UA were used in 90% (27/30) and 88% (15/17) of these facilities, respectively. Conclusion Even among medical facilities in Saga Prefecture that are active in liver cancer surveillance, awareness of UE and UA is not high. The availability of UE and UA may be inadequate, considering the high prevalence of SLD.

Fibrosis-4 (FIB-4) index and genetic polymorphisms have been used in assessing the risk of liver-related events (LRE) in metabolic dysfunction-associated steatotic liver disease (MASLD). To establish a more efficient prediction strategy for LRE, we investigated a combined approach that uses the FIB-4 index and genetic polymorphisms.

We enrolled 1304 Japanese patients with biopsy-proven MASLD in this longitudinal multicenter cohort study. PNPLA3, TM6SF2, GCKR and MBOAT7 genotypes were genotyped, and polygenic risk score high fat content (PRS-HFC) were calculated.

During the follow-up period of 8.1 year, 96 LRE occurred and 53 patients died. PNPLA3, TM6SF2 and GCKR genotypes were associated with LRE development. We divided patients into three groups based on the FIB-4 index and PNPLA3 and TM6SF2 genotype. The cumulative LRE development rate in each group was 2.1%/28.9%/53.5%, respectively, at 10 years. Multivariate analysis revealed hazard ratios (HRs) for LRE of 10.72 in the high-risk group and 4.80 in the intermediate-risk group. Overall survival in each group was 98.8%/85.2%/72.4%, respectively, at 10 years. HRs for prognosis were 8.74 in the high-risk group and 5.62 in the intermediate-risk group. Patients with FIB-4 index > 2.67 and high PRS-HFC had HR of 6.70 for LRE development and HR of 6.07 for prognosis compared to patients with FIB-4 ≤ 2.67.

The approach of measuring the FIB-4 index first followed by assessment of genetic polymorphisms efficiently detected patients at high risk of developing LRE. Therefore, this two-step strategy could be used as a screening method in large populations of patients with MASLD.

We retrospectively examined the benefits and disadvantages of adding imeglimin to metformin therapy in patients with type 2 diabetes.

Ninety-four patients with type 2 diabetes who had been administered imeglimin were included in the safety analysis set (SAS). Sixty-four patients who had been treated with imeglimin for over 6 months were included in the full analysis set (FAS). The primary outcome was the change in HbA1c levels in the FAS. The secondary outcomes were gastrointestinal adverse events (AEs) in the SAS and changes in body weight and FIB-4 in theFAS.

In the SAS, gastrointestinal AEs occurred in 15 of 40 (38%) metformin users and 6 of 54 (11%) non-users. In the FAS, HbA1c levels were significantly reduced in both metformin users (n = 27, baseline, 8.5 ± 1.1%;6 months, 7.7 ± 1.2%) and non-users (n = 37, baseline, 8.0 ± 0.9%; 6 months,7.4 ± 0.9%). While body weight (from 72.0 ± 20.5 kg to 70.9 ± 20.8 kg) and FIB-4 (from 1.27 ± 0.57 to 1.17 ± 0.49) significantly decreased in metformin users, they did not significantly differ in non-users.

Adding imeglimin to metformin therapy demonstrated favorable reductions in HbA1c, body weight, and FIB-4 in patients with type 2 diabetes, although it was associated with the incidence of gastrointestinal AEs.

UMIN000055241.

Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients.

Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated.

Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m2), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups.

Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies. Key Points • RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis. • RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis. • HCQ may provide a protective effect against liver fibrosis in RA patients.

Pharmacotherapy for metabolic dysfunction-associated steatotic liver disease (MASLD) is still under development and has not been fully established. For patients with MASLD and type 2 diabetes, treatment with antidiabetic drugs, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, is recommended, with vitamin E supplementation when treatment efficacy is insufficient. The benefits and risks of SGLT2 inhibitors for MASLD with type 2 diabetes have not been thoroughly investigated.

This prospective randomized controlled trial aimed to elucidate the effectiveness and risks of the SGLT2 inhibitor dapagliflozin in comparison with vitamin E in patients with MASLD and comorbid type 2 diabetes.

The trial enrolled 24 patients with MASLD and comorbid type 2 diabetes, who were assigned to receive either dapagliflozin (5 mg/day) or vitamin E (150 mg/day) for 24 weeks. The primary outcomes included serum levels of AST, ALT, γ-GT, and type IV collagen, and the FIB-4 index. The secondary outcomes were BMI, HbA1c and serum ferritin levels, lipid profile, body composition assessed using InBody, and hepatic fat content and fibrosis evaluated with FibroScan. Adverse events were monitored throughout the study period.

Both groups demonstrated significant reductions in serum AST and ALT levels but intergroup differences were not significant. The dapagliflozin group showed additional benefits, with significant decreases in BMI and HbA1c, γ-GT, ferritin, LDL cholesterol, and body fat levels, indicating improved glycemic control and lipid profile. Dapagliflozin administration was associated with a significant decline in the skeletal muscle index, indicating a risk of muscle loss absent in the vitamin E group. This reduction in muscle mass is clinically significant as it suggests a potential risk of worsened overall survival with dapagliflozin treatment.

This study indicates that dapagliflozin provides several metabolic benefits in patients with MASLD and comorbid type 2 diabetes, including reductions in the levels of liver enzymes and body fat, but the observed decrease in muscle mass suggests a potential adverse effect on long-term survival outcomes. Muscle mass should be monitored in patients receiving dapagliflozin therapy to mitigate the risk of sarcopenia progression and ensure a comprehensive approach to MASLD management.

https://jrct.niph.go.jp/re/reports/detail/81182, identifier jRCT1031180386.

Changes in FIB-4 levels after the initiation of luseogliflozin therapy were compared between patients with type 2 diabetes according to the presence or absence of alcohol consumption.

A total of 192 patients with type 2 diabetes who continued luseogliflozin therapy for over 12 months were retrospectively investigated. The primary outcome was the change in FIB-4. The secondary outcomes were changes in HbA1c, body weight, and serum albumin concentration. A current drinker was defined as an individual consuming >20 g ethanol equivalent/day. Patients were classified according to their risk of developing liver fibrosis into the low-risk (FIB-4 < 1.3) and intermediate/high-risk (FIB-4 ≥ 1.3) groups.

In the low-risk group, while FIB-4 increased dramatically from 0.91 ± 0.30 at the baseline to 1.14 ± 0.34 at 12 months in drinkers (n = 27), non-drinkers (n = 79) showed no significant change (0.87 ± 0.22-0.91 ± 0.26). In the intermediate/high-risk group (n = 63), although the FIB-4 in drinkers (n = 23) showed no significant change (2.18 ± 1.00-2.16 ± 0.93), it significantly decreased from 2.10 ± 0.87 to 1.80 ± 0.68 in non-drinkers (n = 63). In both the low- and intermediate/high-risk groups, HbA1c and body weight significantly decreased in both drinkers and non-drinkers. Serum albumin concentrations significantly increased in both drinkers and non-drinkers in the low-risk group. Although serum albumin concentration did not significantly change in drinkers, it dramatically increased in non-drinkers in the intermediate/high-risk group.

HbA1c levels and body weight decreased in patients with type 2 diabetes after initiating luseogliflozin therapy, regardless of drinking habits. However, it is desirable to limit alcohol consumption when considering its effects on liver fibrosis.

Individuals with metabolic-associated steatotic liver disease (MASLD) have a worse prognosis compared to patients without steatosis, and its prevalence is increasing. However, detailed risk factors based on obesity and sex remain unclear. We aimed to investigate the impact of cardiometabolic risk factors (CMRFs) on the risk of MASLD in individuals without pre-existing SLD.

SLD was diagnosed by ultrasonography. Non-SLD individuals were followed 65,657 person-years. Incidence rates of MASLD were assessed by Kaplan-Meier analysis. Furthermore, independent factors associated with the development of MASLD were identified using Cox regression analysis, stratified by four groups: obese men, non-obese men, obese women, and non-obese women.

The overall incidence rate of MASLD was 39.3/1,000 person-years. The cumulative incidence was highest in obese men, followed by obese women, non-obese men, and non-obese women. Two or more CMRFs increased the risk of MASLD in all groups. Low HDL cholesterol level was the strongest independent risk factor in both obese and non-obese women and hypertriglyceridemia for both obese and non-obese men. The impact of these CMRFs was stronger in non-obese individuals. (HR [95% CI]: women non-obese 1.9 [1.5-2.4], obese 1.4 [1.1-1.8]; men non-obese 2.3 [1.9-2.9], obese 1.5 [1.2-2.0]).

Multiple CMRFs are important to MASLD development, regardless of sex and obesity. In this Japanese cohort, low HDL cholesterol in women and hypertriglyceridemia in men were the most significant risk factors, especially among the non-obese group. These findings suggest that sex-specific CMRFs may play a role in the development of MASLD.

Objective This study assessed the impact of dietary therapy and reduced body weight on the loss of skeletal muscle in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods This was a single-center retrospective observational study. We enrolled 129 patients with MASLD who had undergone dietary therapy at our facility. We assessed skeletal muscle mass using a bioelectrical impedance analysis at the start of dietary treatment and 12 months after the first assessment. Variables related to muscle reduction were analyzed using a logistic regression model. Results One hundred and eighteen cases were analyzed, excluding those with missing data. In the muscle reduction group, there were more subjects with body weight reduction than in the control group (68% and 40%, respectively, p=0.002), and their body mass index (BMI) was decreased (-0.7 kg/m2 and +0.3 kg/m2, respectively, p=0.0003). There was a significant correlation between the changes in the BMI and muscle mass (R=0.48, p<0.0001). We standardized muscle mass change by dividing it by weight change to analyze the severe decrease in muscle mass compared to weight change. A logistic regression analysis revealed that type 2 diabetes mellitus (T2DM) was an independent variable related to severe skeletal muscle loss (odds ratio, 2.69; 95% CI: 1.13-6.42, p=0.03). Conclusion Weight loss is associated with skeletal muscle loss during dietary treatment for MASLD. T2DM is a risk factor for severe skeletal muscle loss.

Adult growth hormone deficiency (AGHD) increases the prevalence of complications, including metabolic disorder, leading to increased cardiovascular mortality from cardiovascular diseases. However, no large database studies have evaluated AGHD patients without GH replacement therapy (GHRT). We investigated the prevalence of AGHD-related complications in patients without GHRT.

Patients with AGHD and associated complications were identified from the Medical Data Vision claims database using Japanese local disease codes mapped to ICD-10 codes. The prevalence of AGHD-related complications in 2020 was estimated to compare with the prevalence in the Japanese general population in the latest available year 2020. Risk factors for complications were evaluated by Kaplan-Meier curves and a Cox proportional hazard model.

We identified 8,809 untreated patients with AGHD from April 2008 to September 2022, including 3,430 in 2020. In 2020, the prevalence of complications was higher in the AGHD population adjusted for sex and age than in the Japanese general population, e.g., diabetes mellitus, 9.3% vs. 3.6%; osteoporosis, 4.8% vs. 1.3%; and dyslipidemia, 22.0% vs. 3.9%. Age was a significant risk factor for most complications, and female sex for osteoporosis. Diabetes mellitus was a significant risk factor for dyslipidemia, ischemic heart disease, cerebrovascular disease, and all-cause death.

Untreated patients with AGHD have a higher prevalence of metabolic complications than the general population despite no difference in their related risk factors. Given the low use of GHRT in this study, comprehensive treatment approaches that include GHRT need to be considered to alleviate the risk of complications.

Lactylation, a novel form of lactate-mediated protein post-translational modification (PTM), has been identified as a crucial regulator of gene expression and protein function through the modification of both histone and non-histone proteins. Liver disease is frequently characterized by a reprogramming of glucose metabolism and subsequent lactate accumulation. Recent research has implicated lactylation in a diverse array of hepatic pathologies, including liver injury, non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Consequently, lactylation has emerged as a pivotal regulatory mechanism in liver disease pathogenesis. This review aims to elucidate the intricate regulatory and functional mechanisms underlying lactylation, synthesize recent advancements in its role in various liver diseases, and highlight its potential as a therapeutic target for future interventions in hepatic disorders.

Background The etiology of liver cancer is changing to metabolic dysfunction-associated steatotic liver disease, and ultrasound elastography is useful for identifying high-risk patients. However, these regional differences remain unclear. We aimed to investigate regional differences in the prevalence of liver cancer and the use of ultrasound elastography in Japan using the National Database of Health Insurance Claims (NDB). Methods We used NDB open data from 2020. The standardized claims data ratio (SCR) was used to evaluate regional differences. We investigated medical receipt information for liver cancer, diabetes-related diseases, and elastography in 47 prefectures. Results The highest SCR for liver cancer was observed in Kyushu (median 134, IQR [109-139]), followed by Chugoku (113, [110-132]), Kinki (109, [89-126]), and Shikoku (107, [100-121]), highlighting a significant concentration in Western Japan (The mean SCR; 114.9 in Western Japan, 88.5 in Eastern Japan: p<0.0001). A higher SCR has also been observed in the treatment of liver cancer, including hepatic resection and radiofrequency ablation, in Western Japan. Similarly, in Western Japan, higher SCRs have also been observed for diabetes-related diseases, such as glucose intolerance, ischemic cardiovascular disease, angina pectoris, and ischemic cerebrovascular disease. However, the SCR for transient elastography and shear wave elastography is low in many prefectures throughout Japan. Conclusion The morbidity of liver cancer and diabetes-related diseases is higher in Western Japan. However, ultrasound elastography is not widely used in Japan. There is an urgent need to promote awareness of ultrasound elastography to screen patients at high risk for liver cancer, particularly in Western Japan.

Non-alcoholic fatty liver disease (NAFLD) and its advanced form, non-alcoholic steatohepatitis (NASH), are the leading causes of chronic liver disease globally. They are driven by complex mechanisms where inflammation plays a pivotal role in disease progression. Current therapies, including lifestyle changes and pharmacological agents, are limited in efficacy, particularly in addressing the advanced stages of the disease. Emerging approaches targeting inflammation, metabolic dysfunction, and fibrosis offer promising new directions, though challenges such as treatment complexity and heterogeneity persist. This review concludes the main therapeutic targets and approaches to manage inflammation currently and emphasizes the critical need for future drug development and combination therapy for NAFLD/NASH management.

The fibrosis-4 index, a noninvasive method for evaluating liver fibrosis, is closely associated with cardiovascular events. In this study, we tested the hypothesis that the fibrosis-4 index is associated with new-onset hypertension in the general population. A total of 15,502 individuals (51.0 ± 13.2 years) who participated in our health checkup program were screened. Participants with hypertension were excluded, and the remaining 8719 normotensive participants (48.4 ± 12.6 years) were followed up (median 1739 days) with the endpoint of the new onset of hypertension. During follow-up, 1750 participants (39.0 per 1000 person-years) developed hypertension. In Kaplan-Meier analysis, where participants were divided into three groups according to the fibrosis-4 index at baseline (low, <1.30; intermediate, 1.30-2.67; high, ≥2.67), the risk of hypertension increased with increasing fibrosis-4 index (low, 33.8; intermediate, 55.2; high, 69.4 per 1000 person-years). Multivariate Cox hazard regression analysis revealed that the log-transformed fibrosis-4 index was independently associated with the development of new hypertension (hazard ratio 4.279, 95% confidence interval 3.318-5.518). These results suggest that the fibrosis-4 index is a useful tool to evaluate a risk of developing hypertension in the general population. Hypertension and liver fibrosis may share a common basis.

Cassia mimosoides L. (CML) is a traditional Chinese medicine (TCM), which is frequently used in the clinical practice of TCM in the Lingnan region of China for the treatment of obesity. However, it is not clear whether decoction of cassia seeds has beneficial effects on non-alcoholic fatty liver disease (NAFLD).

This study investigates the effect of CML on NAFLD and its underlying mechanisms.

The high-fat diet (HFD) was used to induce NAFLD mice, and 40 male C57BL/6J mice were divided into Control, HFD, and CML groups (CML-low 1.5 g/kg, CML-medium 2.25 g/kg, CML-high 4.5 g/kg). The mouse primary hepatocytes (MPHs) of wild type (WT) and PXR-/- mice were induced using OAPA and divided into Control, OAPA, and CML groups (10 mg/L, 100 mg/L). Glycolipid metabolism, inflammation, and oxidative stress levels were detected in vivo and in vitro.

Compared to the HFD group, the CML groups demonstrated reduced body weight, triglycerides, total cholesterol, blood glucose, and mRNA levels of the lipid metabolism genes Srebp-1c and ACC1 in mice (p < 0.05 or 0.01). The ELISA results indicated that CML inhibited the production of IL-1β, IL-6, and TNF-α (p < 0.05). Furthermore, CML increased the SOD level (p < 0.01) to improve oxidative stress. RNA-seq expression showed that CML suppressed the transcriptional level of pregnane X receptor (PXR)(p < 0.05). In vitro experiments, the protective effect of CML against OAPA-induced lipid accumulation and inflammation observed in WT MPHs disappeared in PXR-/- MPHs (IC50: 1.04 mg/mL).

CML decoction ameliorates NAFLD mainly by inhibiting the PXR signaling pathway, which provides a theoretical basis for the broad application of CML in clinical practice.

Myokine is a general term for hormones, peptides, and other substances secreted by skeletal muscle. Myokine has attracted much attention in recent years as a key substance for understanding the mechanism of "exercise and health". Skeletal muscle accounts for about 40% of the total human weight and is now recognized as an endocrine organ that produces myokines, which have physiological activity. Representative myokines include IL-6, myostatin, irisin, brain-derived neurotropic factor, fibroblast growth factor-21, and decorin. On the other hand, sarcopenia, defined by quantitative and qualitative loss of skeletal muscle, is a condition that has received much attention in recent years because of its close correlation with prognosis. In patients with chronic liver disease (CLD), sarcopenia is a common complication. Mechanisms underlying sarcopenia in CLD patients have been reported to involve protein-energy malnutrition, which is characteristic of patients with cirrhosis, signaling involved in protein synthesis and degradation, myokines such as myostatin and decorin, the ubiquitin-proteasome pathway, sex hormones such as testosterone, dysbiosis, and insulin resistance, etc., in addition to aging. Each of these pathological conditions is thought to be intricately related to each other, leading to sarcopenia. This review will summarize the relationship between CLD and myokines.

This longitudinal observational study aimed to evaluate whether cardiometabolic factors and dietary characteristics are determinants of metabolic dysfunction-associated steatotic liver disease (MASLD) in non-obese individuals (body mass index [BMI] < 25 kg/m²). The study was conducted at the Japanese Red Cross Society Kyoto Daiichi Hospital. Clinical data were longitudinally recorded at annual health checks. The diagnosis of MASLD was based on the results of abdominal ultrasonography and cardiometabolic criteria. Lifestyle behaviors and dietary characteristics were assessed using a self-administered questionnaire. A total of 4,100 non-obese middle-aged and older participants (1,636 men and 2,464 women) were followed up for an average of 6.44 ± 4.16 years. During the follow-up period, there were 410 new cases of MASLD in men (25.1%) and 484 in women (19.6%). The incidence rate was higher for men (39.7 per 1,000 person-years) than for women (30.1 per 1,000 person-years). Multivariable-adjusted logistic regression analyses using the rate of change per year with standardized values found that BMI gain was strongly associated with the onset of MASLD for both men (OR: 1.90, 95% CI: 1.64-2.19) and women (OR: 1.95, 95% CI: 1.72-2.21). Increased waist circumference and triglycerides were also associated with MASLD onset for both men and women. Lowering of high-density lipoprotein cholesterol was identified as a risk factor for MASLD in both men and women. Regarding dietary characteristics, the onset of MASLD was significantly and negatively associated with "often eating vegetables" for men (OR: 0.73, 95% CI: 0.57-0.93) and "often eating soy products" for women (OR: 0.71, 95% CI: 0.58-0.88), even after adjusting for BMI change and other covariates. These findings suggest that maintaining body weight and favorable dietary characteristics are key factors in the prevention of MASLD in non-obese individuals.

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) characterized by damage and inflammation of hepatocytes. Some medicinal plants have shown antioxidant and anti-inflammatory effects on liver cells. We aimed to investigate the hepatoprotective effect of Heptex® capsules containing 200 mg of Dukung Anak (a powdered extract from aerial parts of Phyllanthus niruri) and 100 mg of Milk Thistle (a powdered extract from fruits of Silybum marianum) in patients with an apparent risk factor for NASH.

This was a phase II, randomized, double-blind, placebo-controlled, three-arm, interventional clinical trial. Patients were randomized in a 1:1:1 ratio to receive placebo, low dose (one capsule) of Heptex®, or high dose (two capsules) of Heptex®. After 36 weeks, liver enzymes, Fib-4 score, lipid profile, CAP score, and kPa score were evaluated. Patients were monitored for safety throughout the treatment duration.

A total of 146 patients were enrolled in the study. A significant decrease was observed in ALT levels in the low-dose group (57 IU/L to 40 IU/L, p = 0.026) and the high-dose group (61 IU/L to 47.5 IU/L, p < 0.0001) and in AST levels in the high-dose group (43.5 IU/L to 32 IU/L, p = 0.001), with no significant difference between the relative percent change in ALT (p = 0.465) or AST (p = 0.632) between the three groups. No significant difference was revealed between the three groups regarding the median change in Fib-4 score at the end of treatment (p = 0.985). No significant change in the lipid profile was observed in any of the three groups except for the total cholesterol level, which significantly decreased from 210 IU/L to 187 IU/L, p = 0.031 in the low-dose group.

Heptex® capsules were safe and well tolerated over a treatment period of 36 weeks. However, the hepatoprotective effect in patients at risk of NASH still needs further assessment using more accurate investigation tools, a larger sample size, and/ or higher doses of the combination.

Retrospectively registered (registration date: 25/04/2022; trial registration number: NCT05343780).

This study aims to evaluate the current state of family function and self-management abilities in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and analyze the correlation between the two.

Baseline data were collected from 243 patients with MASLD, utilizing the Family Care Index and Self-Management Scale. Multiple linear regression analysis was employed to assess factors influencing self-management in these patients.

The mean score on the Self-Management Scale for the 243 MASLD patients was (92.74 ± 17.22), while the Family Function Scale score was (5.99 ± 1.61). Spearman correlation analysis indicated a positive correlation between family function and scores in disease prevention and control, daily living, disease knowledge, psychological awareness, and unhealthy lifestyle (rs = 0.220, 0.198, 0.227, 0.149, 0.257, 0.266; P < 0.05). Multiple linear regression analysis identified several factors affecting self-management abilities in MASLD patients: smoking history (β'=-0.317), marital status (β'=0.292), family function (β'=0.279), educational level (β'=0.157), severity of fatty liver (β'=0.144), and gender (β'=-0.126) (P < 0.05).

A significant proportion of MASLD patients exhibit family function impairment, which severely affects their self-management abilities. Interventions aimed at improving family function in MASLD patients are necessary to enhance self-management behaviors and improve disease prognosis.

Despite causing significant morbidity and mortality, nonalcoholic fatty liver disease (NAFLD) is underdiagnosed. Clinical indices developed to identify hepatic steatosis are often used by providers but their potential for use at the population level remains unexplored. We assessed clinical phenotypes for their ability to identify potential patients with NAFLD and nonalcoholic steatohepatitis (NASH) in the electronic health record.

We conducted a single-center retrospective cohort study of adult patients from January 1, 2016, to December 31, 2022. We developed 4 phenotypes: clinical NAFLD (C-NAFLD), clinical NASH (C-NASH), NAFLD with diagnosis (D-NAFLD) and NASH with diagnosis (D-NASH) and compared characteristics across them to identify differences between patients with and without International Classification of Diseases diagnoses.

Each of the (C) phenotypes identified a cohort of patients who had clinical evidence suggestive of disease without a documented diagnosis. Black patients were overrepresented in the (C) relative to (D) groups (C-NAFLD 24.3% vs D-NAFLD 21.2%; C-NASH 28.5% vs D-NASH 14.0%). Patients with D-NASH were more likely to be prescribed medications that may be effective in treating NAFLD-NASH spectrum disease, ie, glucagon-like peptide 1 receptor agonists (C-NASH 5.0% vs D-NASH 16.7%, P < .001). Fewer patients with D-NASH had cardiovascular (C-NASH 58.0% vs D-NASH 46.3%, P < .001) and heart failure (C-NASH 33.9% vs D-NASH 24.8%, P < .001) hospitalizations than those with C-NASH.

Noninvasive clinical indices may improve identification of patients with or at risk for NAFLD-NASH at the population level. Systematic differences between populations with and without International Classification of Diseases diagnoses of NAFLD-spectrum disease suggest disparities in the application of screening and diagnostic procedures.

Mac-2 binding protein glycosylation isomer (M2BPGi) is a liver fibrosis biomarker that originated in Japan and has been covered by health insurance for 10 years. M2BPGi is useful not only for liver fibrosis stage prediction but also for assessment of the degree of liver inflammation and prediction of hepatocellular carcinoma development. The usefulness of M2BPGi for assessing disease progression in patients with various chronic liver diseases has been demonstrated over the past decade in a large number of patients. Recently, there have been many reports from outside Japan, including reports from South Korea, Taiwan, Hong Kong, and China. These studies demonstrated that M2BPGi is an excellent biomarker that can evaluate the progression of liver fibrosis in chronic liver disease. It is also an excellent indicator of liver activity. Recently, a quantitative M2BPGi (M2BPGi-Qt) assay was developed, and future validation in real-world settings is expected. This will enable diagnosis of the progression of liver fibrosis based on more precise test results and is expected to contribute to the early detection and follow-up of diseases caused by chronic hepatitis, as well as post-treatment monitoring. The significance of the M2BPGi-Qt assay will likely become clearer as real-world data accumulate. If new cutoff values for each chronic liver disease stage and activity level using the M2BPGi-Qt assay are set based on real-world data, it is expected that this will become a useful tool to identify cases of liver fibrosis and monitor the progression of chronic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prominent liver disease occurring in approximately 25% of the general population. As treatment, lifestyle modification is essential, but there are few reports on dietary patterns associated with MASLD except for the Mediterranean diet. This study examines dietary habits related to MASLD using the fatty liver index (FLI). Longitudinal analysis of a community-based cohort, the Nagahama Prospective Cohort for Comprehensive Human Bioscience, was performed. Dietary habits were assessed by a self-reported questionnaire on food intake frequency, and factor analysis was applied to identify dietary patterns. Multiple regression analysis was performed with baseline FLI or FLI after 5 y as the dependent variable and sex, age, and/or baseline FLI, and factor scores of each dietary pattern as simultaneous independent variables. The same analyses stratified by sex or body mass index (BMI) were also performed. Three thousand five hundred one participants were included. The 15 food items of the questionnaire were summarized into four dietary patterns. Dietary patterns rich in soybean products, vegetables, fish, fruits, and miso soup, which is characteristic of traditional Japanese diet, negatively correlated with FLI and FLI after 5 y (partial regression coefficient: -3.01 and -1.03, respectively; p<0.01 for both). The result was similar in sex-specific analysis and in BMI<23 kg/m2 group, when the participants were stratified according to BMI. Our results suggest that dietary patterns rich in soybean products, vegetables, fish, fruits, and miso soup are protective factors against MASLD especially in individuals with BMI<23 kg/m2.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in patients with obesity and diabetes and can lead to serious complications. This study aimed to evaluate fundus photographs using artificial intelligence to explore the relationships between diabetic retinopathy (DR), MASLD, and related factors. In this cross-sectional study, we included 1,736 patients with a history of diabetes treatment or glycated hemoglobin (HbA1c) levels of ≥6.5%. All participants were negative for hepatitis B surface antigen and hepatitis C virus antibody and were selected from 33,022 examinees at a health facility in Japan. Fundus photographs were analyzed using RetCAD software, and DR scores were quantified. The presence of DR was determined using two cutoffs: sensitivity (CO20) and specificity (CO50). Steatotic liver (SL) stages were assessed via ultrasound and fibrosis indices and classified into three groups: no SL (SL0), SL with low fibrosis (SL1), and SL with high fibrosis (SL2). Odds ratios (ORs) for the risk of DR associated with each SL stage were calculated using logistic regression, adjusted for age, sex, body mass index, HbA1c, C-reactive protein level, and alcohol consumption. The risk of DR was lower in the SL1 (OR: 0.63, 0.54) and SL2 (OR: 0.64, 0.77) groups compared to the SL0 group at CO20 for both the Fibrosis-4 Index (FIB-4) and the non-alcoholic fatty liver disease fibrosis score (NFS), respectively. Additionally, higher levels of cholinesterase were consistently associated with a reduced risk of DR (FIB-4: OR 0.52, NFS: OR 0.54) at CO50. This study demonstrates that MASLD was associated with a reduced risk of DR, with cholinesterase levels providing further protective effects, highlighting the need for further research into the protective mechanisms and refinement of DR evaluation techniques. The standardized AI evaluation method for DR offers a reliable approach for analyzing retinal changes.

Objective A short sleep duration is associated with non-alcoholic fatty liver disease (NAFLD). However, the causal relationship between a short sleep duration and the onset of NAFLD remains unknown because of the lack of any longitudinal studies. Therefore, we evaluated the association between sleep duration and the onset of NAFLD. Methods We evaluated health checkup data for 1,862 NAFLD-free Japanese adults aged 33-86 years at baseline and followed those individuals for a median of 41 months. Hepatic steatosis was examined using ultrasonography (US). The Cox proportional hazards model was used to evaluate the association between sleep duration and NAFLD onset. Results Among the 1,862 participants, 483 (25.9%) developed NAFLD. The proportion of women who developed NAFLD was the highest in the group with a sleep duration of <6 hours and lowest in the group with a sleep duration of 7 to <8 hours. The multivariable-adjusted hazard ratio (95% confidence interval) for the onset of NAFLD in women with a sleep duration <6 hours compared with those with a sleep duration of 7 to <8 hours was 1.55 (1.09-2.20; p=0.02). Conclusion In women, a short sleep duration was independently associated with the onset of NAFLD, thus suggesting that an adequate sleep duration can be a promising preventive factor for the onset of NAFLD in women.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed as nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of obesity and metabolic syndrome. It is mainly caused by insulin resistance. With the increased risk of visceral obesity in South Asians, the prevalence of MASLD is on the rise. The morbidity associated with MASLD and its complications, including hepatocellular carcinoma is projected to increase in this South Asian population.

In this narrative review we explore the diagnosis and management of MASLD in the South Asian population. We summarize the findings from the recent literature on the diagnostic methods and management options for MASLD in this population.

Through our search we found no specific guidelines for the diagnosis and management of MASLD in the South Asian population. The existing general guidelines may not be applied to South Asian populations due to the differences in phenotype, genotype, social and cultural aspects. South Asian countries also have limited resources with the non-availability of newer pharmacotherapeutic agents.

The goal of this review is to guide obesity physicians and primary care providers to have a stepwise approach to treat patients at risk for MASLD with a main focus on interdisciplinary management most applicable to South Asian patients. More research is needed to formulate guidelines and algorithm that are specific for the South Asian population.

Ferroptosis, a distinct form of non-apoptotic cell death characterized by iron dependency and lipid peroxidation, is increasingly linked to various pathological conditions in pregnancy and liver diseases. It plays a critical role throughout pregnancy, influencing processes such as embryogenesis, implantation, and the maintenance of gestation. A growing body of evidence indicates that disruptions in these processes can precipitate pregnancy-related disorders, including pre-eclampsia (PE), gestational diabetes mellitus (GDM), and intrahepatic cholestasis of pregnancy (ICP). Notably, while ICP is primarily associated with elevated maternal serum bile acid levels, its precise etiology remains elusive. Oxidative stress induced by bile acid accumulation is believed to be a significant factor in ICP pathogenesis. Similarly, the liver's susceptibility to oxidative damage underscores the importance of lipid metabolism dysregulation and impaired iron homeostasis in the progression of liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), cholestatic liver injury, autoimmune hepatitis (AIH), acute liver injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). This review discusses the shared signaling mechanisms of ferroptosis in gestational and hepatic diseases, and explores recent advances in understanding the mechanisms of ferroptosis and its potential role in the pathogenesis of gestational and hepatic disorders, with the aim of identifying viable therapeutic targets.

We aimed to clarify the relationship between alanine aminotransferase (ALT) level and body composition in Japanese medical health checkups, especially in cases with ALT ≤ 30 IU/L (7569 men and 9497 women).

We categorized our study cohort into four groups: type A (ALT value ≤ 10 IU/L), type B (11 ≤ ALT value ≤ 20 IU/L), type C (21 ≤ ALT value ≤ 30 IU/L) and type D (ALT value > 30 IU/L (ALT over 30)). We retrospectively compared body composition-related parameters (body mass index (BMI), waist circumference (WC), fat (F) index, fatty liver index (FLI), fat-free (FF) index and F-FF ratio) among the four types.

Type A/B/C/D in men and women was found in 262/3279/2107/1921 and 1549/5736/1495/717 (p < 0.0001). BMI, WC, F-index, FLI, FF index and F-FF ratio were all significantly stratified among the four types, regardless of whether they were male or female and over or under 50 years old.

With a decrease in ALT level in medical health checkups, fat mass decreases, and F-FF ratio decreases, but a decrease in skeletal muscle mass cannot be overlooked.

To evaluate the cost-effectiveness of risk-stratified hepatocellular carcinoma (HCC) screening in diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

A state-transition model from a healthcare payer perspective on a lifetime horizon.

Japan.

A hypothetical cohort of 50-year-old diabetic patients with MASLD risk-stratified according to degree of obesity and progression to cirrhosis. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis (MASH) and MASH cirrhosis are progressive manifestations of this specific type of liver disease.

Abdominal ultrasound (US), US with alpha-fetoprotein (AFP), US with AFP and lectin-reactive alpha-fetoprotein (AFP-L3), CT, extracellular contrast-media-enhanced MRI (ECCM-MRI), gadoxetic acid-enhanced MRI (EOB-MRI) and no screening.

Costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), early-stage HCC cases, advanced-stage HCC cases and HCC-related deaths.

EOB-MRI is the most cost-effective screening method for non-obese diabetic patients with MASH cirrhosis and for obese diabetic patients with MASH and MASH cirrhosis. Cost-effectiveness was sensitive to HCC incidence in non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH, and the adherence rate of HCC screening in obese diabetic patients with MASH. When the semiannual HCC incidence was between 0.008 and 0.0138 in non-obese diabetic patients with MASH cirrhosis, US with AFP was more cost-effective than EOB-MRI. Cost-effectiveness acceptability curves showed that EOB-MRI was 50.7%, 96.0% and 99.9% cost-effective in obese diabetic patients with MASH and non-obese diabetic patients with MASH cirrhosis, and obese diabetic patients with MASH cirrhosis at a willingness-to-pay level of $50 000 per QALY gained. Compared with no screening in 100 000 non-obese diabetic patients with MASH cirrhosis and obese diabetic patients with MASH cirrhosis, EOB-MRI reduced total costs by US$69 million and by US$142 million, increased lifetime effectiveness by 12 546 QALYs and by 15 815 QALYs, detected 17 873 and 21 014 early-stage HCC cases, and averted 2068 and 2471 HCC-related deaths, respectively.

Of all HCC screening methods for diabetic patients with MASH cirrhosis, EOB-MRI yields the greatest cost-saving with the highest QALYs, detects the greatest number of early-stage HCC cases and averts the greatest number of advanced-stage HCC cases and HCC-related deaths. The findings provide important insights for the precise implementation of risk-stratified HCC surveillance to reduce morbidity and mortality and improve the quality of life in diabetic patients with MASLD.

To explore the clinical value of computed tomography (CT) liver-to-spleen (L/S) attenuation ratio in patients with non-alcoholic fatty liver disease (NAFLD) accompanied by atherosclerotic plaque (AP).

This was a single-center, retrospective, observational study of patients who were diagnosed with NAFLD undergoing CT scans at Beijing Changping Hospital of Chinese Medicine from April 2020 to April 2022. Patients were grouped according to whether they had a diagnosis of AP or not. Healthy individuals without NAFLD undergoing CT scans during the same period were also included as a control group. The patients were matched for gender, age, and BMI in a 1:1:1 ratio. Correlations between the CT L/S attenuation ratio, liver function indicators, and blood lipid levels were assessed in the three groups. The predictive value of the CT L/S attenuation ratio was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC) analyses.

Eighty-nine cases in each group. The three groups had significant differences in liver function and blood lipid levels (P<0.05). The CT L/S attenuation ratio in the NAFLD+AP and NAFLD groups was lower than that in the control group and was the lowest in the NAFLD+AP group (P<0.05). There was no significant correlation between the CT L/S attenuation ratio and liver function indicators (P>0.05), but it positively correlated with high-density lipoprotein (HDL) and negatively correlated with low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (P<0.05). The CT L/S attenuation ratio had a high predictive value for NAFLD patients with AP (AUC=0.859).

The CT L/S attenuation ratio in NAFLD patients with AP is significantly reduced and is closely related to the levels of blood lipid indicators. The CT L/S attenuation ratio has a high predictive value for NAFLD patients with AP.

This study aimed to address the diagnostic challenges in distinguishing between alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). We utilized whole-slide imaging technology to conduct a comprehensive digital analysis of liver specimens collected from patients undergoing transplantation. This study included 36 and 17 patients with ALD and MASLD cirrhosis, respectively, who underwent transplantation at our institution. Digital slides were analyzed for fibrosis patterns using FibroNest™. Patient background characteristics were comparable between ALD (n = 36) and MASLD (n = 17) groups, except for sex. The ALD group exhibited thicker collagen per strand, longer and more flexural fibrosis, and a more heterogeneous distribution than the MASLD group. In patients with ALD and concomitant metabolic dysfunction, fiber distribution became relatively uniform, resembling MASLD. Application of the phenotypic fibrosis composite score achieved 100% sensitivity and specificity for ALD/MASLD diagnosis. Digital pathological analysis of the fibrosis patterns showed morphological differences between ALD and MASLD. This approach holds promise for histological differentiation, providing valuable insights beyond the current definitions based solely on alcohol intake. This study emphasizes the potential of digital pathology in refining the diagnostic criteria for hepatic disorders.

The diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) requires at least one of five cardiometabolic criteria. It is unclear whether these criteria can be used as predictors and treatment targets for complications including liver-related events and major adverse cardiovascular events (MACE).

To investigate the relationship between cardiometabolic criteria and complications.

We conducted a nationwide, population-based study of 979,352 patients with MASLD. We investigated relationships between a number of criteria at baseline and liver-related events or MACE risks. In a separate longitudinal analysis, we included patients with five criteria at baseline and investigated the relationship between improving the criteria and the incidence of complications after 1 year.

The cumulative incidence of MACE, but not liver-related events, increased with increasing baseline cardiometabolic criteria. In the longitudinal study, multivariable analysis using patients with five criteria (no improvement) as the reference, adjusted hazard ratios (95% confidence interval) of MACE in patients with 4, 3, 2, and 0-1 criteria (1 to 4-5 criteria improvement) were 0.55 (0.52-0.58, p < 0.001), 0.20 (0.17-0.22, p < 0.001), 0.13 (0.11-0.16, p < 0.001), and 0.06 (0.02-0.3, p < 0.001), respectively. The risk of MACE decreased as the cardiometabolic criteria improved. There was no significant association between improvement of the criteria and liver-related events.

Cardiometabolic criteria can be used as predictors and treatment targets for cardiovascular event risk in MASLD. Developing predictors and therapeutic targets for liver-related events is a future challenge.