1.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
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.
2.Predicting Mortality and Cirrhosis-Related Complications with MELD3.0: A Multicenter Cohort Analysis
Jihye LIM ; Ji Hoon KIM ; Ahlim LEE ; Ji Won HAN ; Soon Kyu LEE ; Hyun YANG ; Heechul NAM ; Hae Lim LEE ; Do Seon SONG ; Sung Won LEE ; Hee Yeon KIM ; Jung Hyun KWON ; Chang Wook KIM ; U Im CHANG ; Soon Woo NAM ; Seok-Hwan KIM ; Pil Soo SUNG ; Jeong Won JANG ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Myeong Jun SONG
Gut and Liver 2025;19(3):427-437
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.
3.Predicting Mortality and Cirrhosis-Related Complications with MELD3.0: A Multicenter Cohort Analysis
Jihye LIM ; Ji Hoon KIM ; Ahlim LEE ; Ji Won HAN ; Soon Kyu LEE ; Hyun YANG ; Heechul NAM ; Hae Lim LEE ; Do Seon SONG ; Sung Won LEE ; Hee Yeon KIM ; Jung Hyun KWON ; Chang Wook KIM ; U Im CHANG ; Soon Woo NAM ; Seok-Hwan KIM ; Pil Soo SUNG ; Jeong Won JANG ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Myeong Jun SONG
Gut and Liver 2025;19(3):427-437
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.
4.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
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.
5.Predicting Mortality and Cirrhosis-Related Complications with MELD3.0: A Multicenter Cohort Analysis
Jihye LIM ; Ji Hoon KIM ; Ahlim LEE ; Ji Won HAN ; Soon Kyu LEE ; Hyun YANG ; Heechul NAM ; Hae Lim LEE ; Do Seon SONG ; Sung Won LEE ; Hee Yeon KIM ; Jung Hyun KWON ; Chang Wook KIM ; U Im CHANG ; Soon Woo NAM ; Seok-Hwan KIM ; Pil Soo SUNG ; Jeong Won JANG ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Myeong Jun SONG
Gut and Liver 2025;19(3):427-437
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.
6.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
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.
7.Predicting Mortality and Cirrhosis-Related Complications with MELD3.0: A Multicenter Cohort Analysis
Jihye LIM ; Ji Hoon KIM ; Ahlim LEE ; Ji Won HAN ; Soon Kyu LEE ; Hyun YANG ; Heechul NAM ; Hae Lim LEE ; Do Seon SONG ; Sung Won LEE ; Hee Yeon KIM ; Jung Hyun KWON ; Chang Wook KIM ; U Im CHANG ; Soon Woo NAM ; Seok-Hwan KIM ; Pil Soo SUNG ; Jeong Won JANG ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Myeong Jun SONG
Gut and Liver 2025;19(3):427-437
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.
8.Catalpa bignonioides extract improves exercise performance through regulation of growth and metabolism in skeletal muscles
Hoibin Jeong ; Dong-joo Lee ; Sung-Pil Kwon ; SeonJu Park ; Song-Rae Kim ; Seung Hyun Kim ; Jae-Il Park ; Deug-chan Lee ; Kyung-Min Choi ; WonWoo Lee ; Ji-Won Park ; Bohyun Yun ; Su-Hyeon Cho ; Kil-Nam Kim
Asian Pacific Journal of Tropical Biomedicine 2024;14(2):47-54
Objective: To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo. Methods: Cell viability was measured using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine (BrdU) assay kit. Western blot analysis was performed to determine the protein expressions of related factors. The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay. Chemical composition analysis was performed using high-performance liquid chromatography (HPLC). Results: Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway. It also induced metabolic changes, increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase. In an in vivo study, the extract-treated mice showed improved motor abilities, such as muscular endurance and grip strength. Additionally, HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength. Conclusions: Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles, suggesting its potential as an effective natural agent for improving muscular strength.
9.Clinical Outcomes of Clipping and Coil Embolization for Ruptured Intracranial Aneurysms Categorized by Region and Hospital Size: A Nationwide Cohort Study in Korea
Yu Deok WON ; Hyoung Soo BYOUN ; Tae Won CHOI ; Sang Hyo LEE ; Young Deok KIM ; Seung Pil BAN ; Jae Seung BANG ; O-Ki KWON ; Chang Wan OH ; Si Un LEE
Journal of Korean Medical Science 2024;39(23):e188-
Background:
To analyze the outcomes of clipping and coiling for ruptured intracranial aneurysms (RIAs) based on data from the National Health Insurance Service in South Korea, with a focus on variations according to region and hospital size.
Methods:
This study analyzed the one-year mortality rates for patients with RIAs who underwent clipping or coiling in 2018. Coiling was further categorized into non-stent assisted coiling (NSAC) and stent assisted coiling (SAC). Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs), or semi-general hospitals (sGHs) based on size. South Korea’s administrative districts were divided into 15 regions for analysis.
Results:
In 2018, there were 2,194 (33.1%) clipping procedures (TRGH, 985; GH, 827; sGH, 382) and 4,431 (66.9%) coiling procedures (TRGH, 1,642; GH, 2076; sGH, 713) performed for RIAs treatment. Among hospitals performing more than 20 treatments, the one-year mortality rates following clipping or coiling were 11.2% and 16.0%, respectively, with no significant difference observed. However, there was a significant difference in one-year mortality between NSAC and SAC (14.3% vs. 19.5%, P = 0.034), with clipping also showing significantly lower mortality compared to SAC (P = 0.019). No significant differences in other treatment modalities were observed according to hospital size, but clipping at TRGHs had significantly lower mortality than at GHs (P = 0.042). While no significant correlation was found between the number of treatments and outcomes at GHs, at TRGHs, a higher volume of clipping procedures was significantly associated with lower total mortality (P = 0.023) and mortality after clipping (P = 0.022).
Conclusion
Using Korea NHIS data, mortality rates for RIAs showed no significant variation by hospital size due to coiling’s prevalence. However, differences in clipping outcomes by hospital size and volume in TRGH highlight the need for national efforts to improve clipping skills and standardization. Additionally, the higher mortality rate with SAC emphasizes the importance of precise indications for its application.
10.Local ablation for hepatocellular carcinoma: 2024 expert consensus-based practical recommendation of the Korean Liver Cancer Association
Seungchul HAN ; Pil Soo SUNG ; Soo Young PARK ; Jin Woong KIM ; Hyun Pyo HONG ; Jung-Hee YOON ; Dong Jin CHUNG ; Joon Ho KWON ; Sanghyeok LIM ; Jae Hyun KIM ; Seung Kak SHIN ; Tae Hyung KIM ; Dong Ho LEE ; Jong Young CHOI ;
Journal of Liver Cancer 2024;24(2):131-144
Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the firstline treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and posttreatment management of patients.

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