ABSTRACT Background Lean metabolic dysfunction‐associated steatotic liver disease (MASLD) is increasingly recognized. Whether it represents a distinct entity or a phenotype within the MASLD spectrum remains unclear. We examined differences in risk factor contribution and metabolic trajectories. Methods In a longitudinal health checkup cohort (2017–2025), we included individuals without hepatic steatosis at baseline and excluded those with alcohol intake at or above the MetALD threshold. Incident MASLD was classified at diagnosis as Obese or Lean MASLD based on obesity status (BMI/WC). Baseline risk factors were evaluated using time‐to‐event and competing‐risk models with interaction testing. Longitudinal metabolic changes were assessed using logistic regression, and repeated trajectories were examined using linear mixed‐effects models. Results Among 13,624 participants, 1865 developed incident MASLD (Obese MASLD, n = 1469; Lean MASLD, n = 396). Male sex, baseline obesity, glycemic abnormality/diabetes, hypertension, hypertriglyceridemia, and higher baseline ALT were independently associated with incident MASLD. Interaction analyses showed a stronger contribution of male sex and weaker contributions of hypertension and low HDL‐C in Lean MASLD. Longitudinal analyses showed Δtriglycerides and ΔALT were consistently associated with incident MASLD in both phenotypes, whereas ΔBMI showed a stronger association with Obese MASLD. Conclusions Lean MASLD shared a broadly similar cardiometabolic risk structure with Obese MASLD, whereas the relative contribution of risk factors differed between phenotypes. Male sex showed a stronger association with Lean MASLD, whereas longitudinal changes in triglycerides and ALT were consistently associated with incident MASLD across both phenotypes. These findings provide exploratory evidence of phenotype‐specific metabolic associations requiring validation before clinical application.
Background and Aims Although the widespread use of direct-acting antivirals (DAAs) has reduced the proportion of hepatitis C virus (HCV) antibody-positive patients eligible for antiviral treatment, the current proportion requiring referral for DAA therapy in ophthalmology departments, which have both high testing volumes and high HCV antibody-positive rates, remains unclear.Methods This nationwide multicenter retrospective cohort study included HCV antibody-positive patients identified through testing in ophthalmology departments at 20 institutions in Japan between 2019 and 2023. The proportions of patients requiring referral for DAA therapy were assessed by electronic medical record (EMR) review across all 20 institutions and by a combination of EMR review and HCV antibody titer determination across nine institutions where antibody titers could be measured.Results A total of 2792 HCV antibody-positive patients were identified across 20 institutions. Based on EMR review, the proportions requiring referral for DAA therapy were 44.4%, 38.7%, 34.2%, 38.9%, and 42.5% in 2019, 2020, 2021, 2022, and 2023, respectively. Among 1255 HCV antibody-positive patients from 9 institutions where HCV antibody titers could be determined, the corresponding proportions assessed by combined EMR review and antibody titer determination were 28.4%, 23.7%, 20.8%, 22.4%, and 25.9%, respectively. Despite a decline in HCV antibody-positive rates over time, the proportion requiring referral remained high.Conclusions Although the number of HCV antibody-positive patients in ophthalmology departments has decreased, a considerable proportion could still be considered for DAA therapy. Combining HCV antibody titer determination with EMR review improves the efficiency of identifying patients requiring referral.
Aims This study investigated the prognostic performance of the FIB-3 index, composed of aspartate aminotransferase, alanine aminotransferase, and platelet count, in patients with decompensated cirrhosis and overt hepatic encephalopathy receiving rifaximin therapy. Methods Between March 2017 and March 2024, 235 patients were included in this multicenter retrospective study. The discriminatory performance of the FIB-3 index for predicting 48-month survival was compared with that of the FIB-4 index, aMAP score, MELD 3.0 score, and Child-Pugh classification. Results The AUROCs for the FIB-3 index, FIB-4 index, aMAP score, MELD 3.0 score, and Child-Pugh classification were 0.63, 0.58, 0.57, 0.71, and 0.70, respectively. Using the FIB-3 index as the reference model, no statistically significant differences in AUROC were observed between the FIB-3 index and the other models (p = 0.05, 0.2, 0.1, and 0.1, respectively). In the NRI analysis, the FIB-3 index demonstrated significantly better discriminatory performance than the FIB-4 index (p < 0.001) but poorer discriminatory performance than Child-Pugh classification (p < 0.001), whereas no significant differences were observed compared with the aMAP or MELD 3.0 scores (p = 0.2 and 0.1, respectively). In the IDI analysis, the FIB-3 index showed significantly better discriminatory performance than the FIB-4 index (p = 0.02) but poorer discriminatory performance than the MELD 3.0 score and Child-Pugh classification (p = 0.004 and p < 0.001, respectively). Conclusions The FIB-3 index showed better prognostic discrimination than the FIB-4 index and may serve as a simple age-independent fibrosis-related marker that complements established liver function-based prognostic models.
Aim: In Fontan-associated liver disease (FALD), chronic congestion often confounds conventional fibrosis markers, complicating surveillance for hepatocellular carcinoma (HCC). Although lymphatic dysfunction is fundamental to Fontan physiology, its contribution to hepatocarcinogenesis remains unclear. We aimed to investigate how lymphatic congestion, quantified by cisterna chyli (CC) dilation, is associated with liver nodules and HCC. Methods: We retrospectively analyzed 77 patients with FALD who underwent cardiac catheterization and contrast-enhanced computed tomography or magnetic resonance imaging. Clinical, hemodynamic, and lymphatic parameters were evaluated to identify factors independently associated with liver nodules. HCC-related analyses were carried out exploratorily because of the limited number of HCC cases. Results: Liver nodules were identified in 43 patients (55.8%), including six patients with HCC. CC diameter was 3.2 mm, 4.1 mm, and 6.6 mm in the non-nodule, nodule without HCC, and HCC groups, respectively (p < 0.0001). In multivariable analysis, larger CC diameter and higher total bile acid (TBA) levels were independently associated with liver nodules, whereas anticoagulant therapy showed an inverse trend. Exploratory analyses suggested an association between larger CC diameter and HCC. CC diameter showed positive correlations with central venous pressure indices and TBA, suggesting a relationship between CC enlargement and the hemodynamic and hepatic abnormalities of FALD. Conclusion: CC dilation was associated with liver nodules in FALD and may reflect lymphatic and hemodynamic burden related to chronic venous congestion. Its potential association with HCC requires validation in larger prospective cohorts.
AIM:Cachexia in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) is associated with poor outcomes. Although C-reactive protein (CRP) is used for diagnosis, its limited specificity may hinder detection of cachexia without systemic inflammation. Leucine-rich α2-glycoprotein 1 (LRG1) may identify cachexia when CRP is low; however, its significance in LC and HCC remains unclear. METHODS:We retrospectively enrolled 243 patients with LC and/or HCC. Cachexia was defined according to the Asian Working Group for Cachexia criteria. Serum LRG1 levels were measured, and associations with cachexia, CRP, and survival were analyzed. Receiver operating characteristic curve analysis determined the optimal LRG1 cutoff. RESULTS:Cachexia, observed in 65 patients (26.7%), was independently associated with shorter survival. Serum LRG1 levels were higher in patients with cachexia than in those without (median, 16.70 vs. 11.55 μg/mL; p < 0.001). Although LRG1 correlated with CRP, high LRG1 was observed in some patients with low CRP. In multivariable analysis, LRG1 remained independently associated with cachexia (odds ratio, 1.060; 95% confidence interval, 1.000-1.130; p = 0.045). The optimal LRG1 cutoff was 15.2 μg/mL; cachexia was more frequent in patients with high LRG1 than in those without (48.75% vs. 15.95%, p < 0.001). Among patients with cachexia having low CRP, 37.5% had high LRG1. In the low-CRP subgroup, LRG1 remained independently associated with cachexia. CONCLUSIONS:Serum LRG1 is associated with cachexia in LC and/or HCC and may provide clinically relevant information not captured by CRP. LRG1 assessment may improve recognition and stratification of cachexia, even in patients with low CRP levels.
