Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background: Serum calcium and magnesium levels are a key factor of the coagulation cascade and may potentially contribute to the pathophysiology of intracerebral hemorrhage (ICH) expansion. The aim of this study was to attain and sustain target levels of serum calcium and magnesium for three days following admission. Methods: A single-blind, prospective, multicenter randomized study was conducted from 2019 to 2022 years, enrolling acute ICH patients aged 18–80 years, with radiological diagnosis and without surgical intervention. Participants were randomly assigned in a 1:1 ratio to either the study group or the control group. In the study group, the target serum levels of calcium (9–10.2 mg/dL) and magnesium (2–3 mg/dL) were actively achieved and maintained for a duration of 3 days following admission. The primary outcome was the expansion of ICH volume within the first 3 days between the study group and the control groups. Results: After implementing inclusion/exclusion criteria, 105 of 354 patients remained in the study. There were no significant differences in ICH volume on hospital days 2 and 3 between the groups. Admission factors including Glasgow coma scale score, hemoglobin level, ICH volume, and spot sign showed significant correlations in multivariate analysis. On the third day of hospitalization, admission serum magnesium levels showed a significant correlation with ICH expansion, whereas calcium levels did not. Conclusion Admission serum magnesium levels were found to correlate with hematoma expansion in patients with acute ICH. While magnesium itself may not be a direct therapeutic target, it could serve as a valuable indicator for identifying potential therapeutic strategies aimed at preventing ICH volume increase.

Background: Serum calcium and magnesium levels are a key factor of the coagulation cascade and may potentially contribute to the pathophysiology of intracerebral hemorrhage (ICH) expansion. The aim of this study was to attain and sustain target levels of serum calcium and magnesium for three days following admission. Methods: A single-blind, prospective, multicenter randomized study was conducted from 2019 to 2022 years, enrolling acute ICH patients aged 18–80 years, with radiological diagnosis and without surgical intervention. Participants were randomly assigned in a 1:1 ratio to either the study group or the control group. In the study group, the target serum levels of calcium (9–10.2 mg/dL) and magnesium (2–3 mg/dL) were actively achieved and maintained for a duration of 3 days following admission. The primary outcome was the expansion of ICH volume within the first 3 days between the study group and the control groups. Results: After implementing inclusion/exclusion criteria, 105 of 354 patients remained in the study. There were no significant differences in ICH volume on hospital days 2 and 3 between the groups. Admission factors including Glasgow coma scale score, hemoglobin level, ICH volume, and spot sign showed significant correlations in multivariate analysis. On the third day of hospitalization, admission serum magnesium levels showed a significant correlation with ICH expansion, whereas calcium levels did not. Conclusion Admission serum magnesium levels were found to correlate with hematoma expansion in patients with acute ICH. While magnesium itself may not be a direct therapeutic target, it could serve as a valuable indicator for identifying potential therapeutic strategies aimed at preventing ICH volume increase.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background: Serum calcium and magnesium levels are a key factor of the coagulation cascade and may potentially contribute to the pathophysiology of intracerebral hemorrhage (ICH) expansion. The aim of this study was to attain and sustain target levels of serum calcium and magnesium for three days following admission. Methods: A single-blind, prospective, multicenter randomized study was conducted from 2019 to 2022 years, enrolling acute ICH patients aged 18–80 years, with radiological diagnosis and without surgical intervention. Participants were randomly assigned in a 1:1 ratio to either the study group or the control group. In the study group, the target serum levels of calcium (9–10.2 mg/dL) and magnesium (2–3 mg/dL) were actively achieved and maintained for a duration of 3 days following admission. The primary outcome was the expansion of ICH volume within the first 3 days between the study group and the control groups. Results: After implementing inclusion/exclusion criteria, 105 of 354 patients remained in the study. There were no significant differences in ICH volume on hospital days 2 and 3 between the groups. Admission factors including Glasgow coma scale score, hemoglobin level, ICH volume, and spot sign showed significant correlations in multivariate analysis. On the third day of hospitalization, admission serum magnesium levels showed a significant correlation with ICH expansion, whereas calcium levels did not. Conclusion Admission serum magnesium levels were found to correlate with hematoma expansion in patients with acute ICH. While magnesium itself may not be a direct therapeutic target, it could serve as a valuable indicator for identifying potential therapeutic strategies aimed at preventing ICH volume increase.