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.
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.
AIM:Radiofrequency ablation (RFA) is curative therapy for early-stage hepatocellular carcinoma (HCC), but a rare subset of patients develop aggressive intrasegmental recurrence shortly after complete ablation. We characterized the incidence, risk factors, and absolute risk. METHODS:This single-center retrospective study included consecutive patients with HCC treated with RFA from August 2002 to December 2024. Rapid progression was defined as recurrence at the ablation margin within 6 months that precluded further locoregional therapy. Cases were matched 1 to 4 with controls based on treatment era, prior RFA sessions, tumor diameter, and tumor number. Preablation imaging and tumor marker dynamics were compared, and absolute risk was estimated. RESULTS:Among 3163 patients who underwent 10,240 RFA treatments, 20 (0.20%) met criteria for rapid progression. Aggressive imaging features including nonsmooth margins (OR 5.87, 95% CI 1.80-19.12) and multinodular confluent growth (OR 3.84, 95% CI 1.30-11.36) were significantly more common in the rapid progression group, though positive predictive values remained below 1%. Irregular rim-like hyperenhancement was present in 15% of rapid progression cases but was absent in all controls. Periportal location accounted for half of the rapid progression cases (OR 2.84, 95% CI 0.97-8.29). Tumor markers including alpha-fetoprotein and des-gamma-carboxy prothrombin declined after RFA in controls but not in the rapid progression group. CONCLUSIONS:Aggressive imaging features and insufficient post-ablation tumor marker decline were associated with rapid progression, though individual predictive value was low. Tumor marker trends may help guide surveillance and earlier transition to systemic therapy.
BACKGROUND:Total ischemic time (TIT) is a key determinant of outcomes after deceased-donor liver transplantation (DDLT). In Japan, the nationwide organ allocation system, which does not include regional prioritization, often requires long-distance graft transport. However, the contributions of transport time, distance, and modality to TIT and post-transplant outcomes have not been fully clarified. METHODS:We performed a nationwide retrospective cohort study of DDLT cases in Japan between July 2019 and December 2023 using data from the Japan Organ Transplant Network. Associations among transport-related factors, TIT, and post-transplant outcomes were assessed. RESULTS:Among the 415 transplant recipients, TIT was significantly correlated with both transport time and transport distance (p < 0.01), although the strength of these correlations varied according to transport modality. Strong correlations were observed for ground and high-speed rail transportation, whereas the correlation was weaker for air transportation. Restricted cubic spline analyses demonstrated strong, monotonic associations between prolonged TIT and increased mortality risk and between prolonged transport time and mortality risk. Prolonged TIT was independently associated with poorer survival in the multivariable analysis, whereas transport time and modality were not. In the analyses stratified by the combination of TIT and transport time, favorable outcomes were observed in cases with a prolonged transport time when TIT was maintained at a lower level. CONCLUSION:Prolonged transport time contributes to increased TIT; however, optimization of perioperative management to minimize TIT may preserve post-transplantation outcomes in long-distance transplantation.
