Kazuyoshi Kon

Background: Spleen stiffness (SS) is a noninvasive marker of portal hypertension; however, the clinical significance of early changes in SS after endoscopic treatment for esophageal varices remains unclear. We evaluated whether SS and its early post-treatment changes are associated with variceal recurrence. Methods: This retrospective pilot study included 20 patients who underwent endoscopic treatment for esophageal varices. Liver stiffness (LS) and spleen stiffness (SS) were measured before treatment, approximately 1 week after the final treatment session (1W), and at 1 month and 1 year after treatment. The clinical outcome of interest was variceal recurrence within 1 year. Early changes in stiffness were calculated from 1W to 1M (Δ1M − 1W). Results: Eleven patients (55.0%) developed variceal recurrence. LS did not differ significantly between the non-recurrence and recurrence groups at any time point during follow-up. SS was comparable between the groups before treatment and at 1W but was significantly higher in the recurrence group at 1M (median [IQR], 2.75 [2.70–2.86] vs. 3.40 [3.06–3.81] m/s in the non-recurrence and recurrence groups, respectively; p = 0.003). ΔSS-VTQ (1M − 1W) was significantly greater in the recurrence group than in the non-recurrence group (−0.13 [−0.62–−0.04] vs. 0.25 [−0.05–0.40] m/s, respectively; p = 0.013), whereas no significant between-group differences were observed in changes in LS. Conclusions: SS at 1 month after endoscopic treatment and its early post-treatment change were associated with variceal recurrence. Serial assessment of SS may provide useful information for early post-treatment risk assessment, although validation in larger prospective studies is needed.

Metabolic dysfunction‐associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disease worldwide, with an increasing number of patients progressing to cirrhosis and hepatocellular carcinoma (HCC). Early identification of individuals at high risk for advanced fibrosis is essential for preventing liver‐related events and improving long‐term outcomes. This guideline summarizes current evidence and provides practical recommendations for the diagnosis, risk stratification, and management of MASLD in clinical practice. These recommendations were developed through systematic evaluation of the literature and expert consensus. Diagnostic approaches, including noninvasive fibrosis assessment tools, imaging, biochemical testing, and indications for referral to gastroenterology/hepatology specialists, were reviewed. Advanced fibrosis is the major determinant of liver‐related morbidity and mortality in MASLD. The Fibrosis‐4 (FIB‐4) index is a widely accessible and reliable first‐line noninvasive tool for fibrosis risk stratification. Patients with elevated FIB‐4 values or clinical features suggestive of progressive liver injury should undergo secondary assessment with elastography and be referred to a specialist when appropriate. Liver biopsy is not routinely required for the diagnosis of MASLD but remains essential for establishing a definitive diagnosis of at‐risk metabolic dysfunction–associated steatohepatitis (MASH), assessing inflammatory activity, resolving discrepancies between noninvasive tests, and differentiating MASLD from other chronic liver diseases. Lifestyle modification remains the foundation of management, with pharmacological therapy considered for patients with a high likelihood of at‐risk MASH. MASLD represents a heterogeneous disease spectrum in which advanced fibrosis is the key prognostic factor. These guideline recommendations aim to standardize clinical practice and support evidence‐based management of MASLD in Japan.

Background: Esophagogastric variceal (EGV) bleeding is a serious complication of pediatric‐onset liver disease; however, evidence regarding endoscopic management and long‐term outcomes remains limited. This study aimed to evaluate clinical outcomes following endoscopic therapy for pediatric EGV and to clarify challenges related to adherence and transitional care. Methods: We retrospectively reviewed patients with pediatric‐onset liver disease who underwent endoscopic treatment for EGV between 2012 and 2024. Patients were categorized into a childhood group (≤ 15 years) and a young adult group (> 15 years). Clinical characteristics, treatment outcomes, retreatment, survival, and adherence during the transition to adult care were analyzed. Results: Emergency endoscopy for hematemesis was common in the childhood group. Despite frequent recurrence, endoscopic therapy was effective and no rebleeding or deaths occurred. In contrast, young adults showed significantly poorer survival (1‐year 84.6%; 2‐year 69.2%; and p = 0.045), primarily due to hepatic decompensation. Nearly half self‐discontinued follow‐up during the transition period, and nonadherence was associated with higher Child–Pugh and MELD scores and markedly reduced survival (5‐year 33.3% and p = 0.038). Some young adults later developed alcohol‐related liver disease, with significantly worse outcomes than the childhood group ( p = 0.023). Conclusions: Endoscopic therapy is effective and safe for pediatric EGV, although recurrence is common. In young adults, long‐term outcomes are determined more by adherence and successful transitional care than by variceal severity. Structured transitional programs are essential for preventing loss to follow‐up and improving survival in pediatric‐onset portal hypertension.

Aim: The COVID‐19 pandemic markedly affected lifestyle behaviors and metabolic health worldwide. Patients with chronic liver disease (CLD) are particularly vulnerable to such disruptions; however, how these effects changed after daily life returned to normal remains unclear. This study examined changes in body composition, hepatic steatosis, and liver fibrosis during the with‐COVID‐19 and after‐COVID‐19 periods, with a focus on potential sex‐specific differences. Methods: A total of 187 patients with CLD underwent FibroScan and bioelectrical impedance analysis at three time points: before COVID‐19 (2019–2020), during the pandemic (2020–2021), and after the disease was reclassified as Category V in Japan (2023–2024). Changes in obesity, hepatic steatosis, and skeletal muscle mass, as well as their associations with liver stiffness, were evaluated using univariate and multivariate analyses. Results: Obesity and hepatic steatosis worsened during the pandemic but improved in the after‐COVID‐19 period, particularly in men. Overall skeletal muscle mass remained stable, whereas lower‐limb muscle mass increased in women. The skeletal muscle index‐to‐BMI ratio increased in both sexes, showing relative preservation of muscle mass. In univariate analyses, changes in liver stiffness (ΔLSM) were associated with muscle mass parameters only in women; however, these associations did not remain significant as independent predictors after multivariate adjustment. Conclusions: As lifestyles normalized after the pandemic, patients with CLD showed improvements in obesity and hepatic steatosis. Women demonstrated recovery of lower‐limb muscle mass, suggesting greater susceptibility to pandemic‐related lifestyle changes. Although muscle mass changes were not independently associated with liver stiffness in multivariate analyses, these findings should be interpreted cautiously; nonetheless, they suggest that sex‐specific factors may warrant consideration when supporting comprehensive health management in patients with CLD.

Introduction: 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.Objective: 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.Methods: 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.Results: 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.Conclusion: 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.Clinical trial registration: https://jrct.niph.go.jp/re/reports/detail/81182, identifier jRCT1031180386.

Aim: Following the coronavirus disease outbreak, a state of public emergency was declared worldwide, which enforced lifestyle changes. This study therefore aimed to investigate the changes in lifestyle, body composition, hepatic steatosis, and fibrosis in patients with chronic liver disease (CLD) under lockdown.Methods: During the lockdown period, 1344 patients with CLD answered a lifestyle questionnaire. In 298 patients, body composition and liver stiffness measure (LSM)/controlled attenuation parameter (CAP) were analyzed by InBody and FibroScan, respectively, and serial data were obtained in 137 patients.Results: More than half of the CLD patients answered decreases in physical activity and frequency of outings during lockdown, while diet was less affected. Overall, 58% of patients showed elevations in CAP values, which were not different statistically over time. Women, but not men, were more likely to increase CAP values during lockdown. Neither LSM nor serum fibrosis markers were elevated chronologically during lockdown. In men, body mass index (BMI), body fat percentage, and visceral fat area (VFA) were significantly increased, whereas in women, lower‐limb muscle mass was significantly decreased. Patients with decreased SMI showed elevations in CAP and VFA values, and patients who exercised less showed increases in BMI.Conclusion: In response to lockdown, men tended to increase body fat but the degree of hepatic steatosis was less affected, while women were more likely to exacerbate hepatic steatosis with skeletal muscle loss among CLD patients. Gender‐specific approaches need to be established for management of CLD patients to avoid exacerbation or comorbidity of steatotic liver disease.

Background The prevalence of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated/related liver disease (ALD) with metabolic syndrome is increasing globally. Metabolic syndrome and excessive alcohol consumption synergically exacerbate liver pathologies; therefore, drinking-specific serum markers unaffected by liver injury or metabolic syndrome are essential for assessing alcohol consumption. We evaluated the ratio of carbohydrate-deficient transferrin to total transferrin (%CDT) in patients with fatty liver disease, particularly focusing on its correlation with metabolic factors (UMIN000033550). Methods A total of 120 patients with fatty liver disease, including ALD and NAFLD, were screened for alcohol misuse using the Alcohol Use Disorders Identification Test. Associations of metabolic syndrome-related factors and hepatic steatosis/liver stiffness with drinking markers, such as %CDT, gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV), were assessed using multiple linear regression analyses. Results %CDT significantly increased with 3–4 drinks/day. The optimal cutoff value for identifying non- to light drinkers was 1.78% (sensitivity, 71.8%; specificity, 83.7%; and area under the receiver operating characteristic curve [AUROC], 0.851), which was significantly higher than that for GGT. The cutoff value for identifying heavy drinkers was 2.08% (sensitivity, 65.5%; specificity, 86.8%; and AUROC, 0.815). Multiple regression analysis revealed that this proportion was negatively correlated with body mass index, whereas GGT and MCV were influenced by multiple factors involved in liver injury and dyslipidemia. Conclusions %CDT showed a strong correlation with alcohol consumption, independent of liver damage, steatosis/stiffness, or metabolic syndrome-related factors, indicating that it is a useful drinking marker for the accurate diagnosis of NAFLD and ALD. Graphical abstract

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated/related liver disease (ALD) with metabolic syndrome is globally increasing. Metabolic syndrome and excessive alcohol consumption synergically exacerbate liver pathologies; therefore, drinking-specific serum markers unaffected by liver injury or metabolic syndrome are essential to assess alcohol consumption. We evaluated the ratio of carbohydrate-deficient transferrin to total transferrin (%CDT) in patients with fatty liver disease, particularly focusing on its correlation with metabolic factors (UMIN000033550). MethodsA total of 120 patients with fatty liver disease, including ALD and NAFLD, were screened for alcohol misuse using the Alcohol Use Disorders Identification Test. Associations of metabolic syndrome-related factors and hepatic steatosis/liver stiffness with drinking markers such as %CDT, gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV) were assessed using multiple linear regression analyses. Results%CDT significantly increased with 3–4 drinks/day. The optimal cut-off value for identifying non- to light drinkers was 1.78% (sensitivity, 71.8%; specificity, 83.7%; area under the receiver operating characteristic curve [AUROC], 0.851), which was significantly higher than that for GGT. The cut-off value for identifying heavy drinkers was 2.08% (sensitivity, 65.5%; specificity, 86.8%; AUROC, 0.815). Multiple regression analysis revealed that this proportion was negatively correlated with body mass index, whereas GGT and MCV were influenced by multiple factors involved in liver injury and dyslipidemia. Conclusions%CDT showed a strong correlation with alcohol consumption, independent of liver damage, steatosis/stiffness, or metabolic syndrome-related factors, indicating that it is a useful drinking marker for the accurate diagnosis of NAFLD and ALD.