1.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
2.Effects of hepatic fibrosis on the quantification of hepatic steatosis using the controlled attenuation parameter in patients with chronic hepatitis B
Hee Jun PARK ; Hyo Jeong KANG ; So Yeon KIM ; Seonghun YOON ; Seunghee BAEK ; In Hye SONG ; Hyeon Ji JANG ; Jong Keon JANG
Ultrasonography 2025;44(1):83-91
Purpose:
This study assessed the impact of hepatic fibrosis on the diagnostic performance of the controlled attenuation parameter (CAP) in quantifying hepatic steatosis in patients with chronic hepatitis B (CHB).
Methods:
CHB patients who underwent liver stiffness measurement (LSM) and CAP assessment using transient elastography before liver resection between 2019 and 2022 were retrospectively evaluated. Clinical data included body mass index (BMI) and laboratory parameters. The histologically determined hepatic fat fraction (HFF) and fibrosis stages were reviewed by pathologists blinded to clinical and radiologic data. The Pearson correlation coefficient between CAP and HFF was calculated. The diagnostic performance of CAP for significant hepatic steatosis (HFF ≥10%) was assessed using areas under the receiver operating curve (AUCs), stratified by fibrosis stages (F0-1 vs. F2-4). Factors significantly associated with CAP were determined by univariable and multivariable linear regression analyses.
Results:
Among 399 CHB patients (median age 59 years; 306 men), 16.3% showed significant steatosis. HFF ranged from 0% to 60%. Of these patients, 9.8%, 19.8%, 29.3%, and 41.1% had fibrosis stages F0-1, F2, F3, and F4, respectively. CAP positively correlated with HFF (r=0.445, P<0.001). The AUC of CAP for diagnosing significant steatosis was 0.786 (95% confidence interval [CI], 0.726 to 0.845) overall, and significantly lower in F2-4 (0.772; 95% CI, 0.708 to 0.836) than in F0-1 (0.924; 95% CI, 0.835 to 1.000) (P=0.006). Multivariable analysis showed that BMI (P<0.001) and HFF (P<0.001) significantly affected CAP, whereas LSM and fibrosis stages did not.
Conclusion
CAP evaluations of significant hepatic steatosis are less reliable in CHB patients with significant or more advanced (F2-4) than with no or mild (F0-1) fibrosis.
3.A prospective comparison of two ultrasound attenuation imaging modes using different frequencies for assessing hepatic steatosis
Hyeon Ji JANG ; Jong Keon JANG ; Subin HEO ; Boyeon KOO ; In Hye SONG ; Hee Jun PARK ; Seonghun YOON ; So Yeon KIM
Ultrasonography 2025;44(3):202-211
Purpose:
This study compared the diagnostic performance of two attenuation imaging (ATI) modes—low-frequency (3 MHz) and high-frequency (4 MHz)—for assessing hepatic steatosis, with histopathological hepatic fat fraction (HFF) as the reference standard.
Methods:
This prospective single-center study enrolled participants with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) scheduled for liver biopsy or surgery between June 2023 and June 2024. Attenuation coefficient (AC) values were consecutively measured using low- and high-frequency ATI modes, while the skin-to-region of interest distance (SRD) was measured simultaneously. Spearman correlation analysis evaluated the relationships of AC with HFF and SRD, and linear regression identified factors affecting AC. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUROC).
Results:
In total, 119 participants (mean age, 37.2±12.0 years; 87 men) were included, with 73 (61.3%) diagnosed with MASLD. HFF ranged from 0% to 50%. The AC values in the lowfrequency mode were significantly higher than those in the high-frequency mode (0.61 vs. 0.54 dB/cm/MHz, P<0.001). HFF significantly influenced AC in both modes, whereas SRD affected AC only in the high-frequency mode (P<0.001). AC correlated positively with HFF in both modes (rs≥0.514, P<0.001) and negatively with SRD in the high-frequency mode (rs=-0.338, P<0.001). The AUROC for hepatic steatosis did not differ significantly between the two modes (0.751 vs. 0.771; P=0.609).
Conclusion
The low-frequency mode produced higher AC values than the high-frequency mode and demonstrated comparable diagnostic accuracy for assessing hepatic steatosis. Unlike the high-frequency mode, the low-frequency mode was not influenced by SRD.
4.Hepatocellular carcinoma in Korea: an analysis of the 2016-2018 Korean Nationwide Cancer Registry
Jihyun AN ; Young CHANG ; Gwang Hyeon CHOI ; Won SOHN ; Jeong Eun SONG ; Hyunjae SHIN ; Jae Hyun YOON ; Jun Sik YOON ; Hye Young JANG ; Eun Ju CHO ; Ji Won HAN ; Suk Kyun HONG ; Ju-Yeon CHO ; Kyu-Won JUNG ; Eun Hye PARK ; Eunyang KIM ; Bo Hyun KIM
Journal of Liver Cancer 2025;25(1):109-122
Background:
s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018.
Methods:
Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018.
Results:
The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%).
Conclusions
Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.
5.Insights into hepatocellular adenomas in Asia: molecular subtypes, clinical characteristics, imaging features, and hepatocellular carcinoma risks
Subin HEO ; In Hye SONG ; Edouard REIZINE ; Maxime RONOT ; Jean-Charles NAULT ; Hae Young KIM ; Sang Hyun CHOI ; So Yeon KIM
Journal of Liver Cancer 2025;25(1):67-78
Hepatocellular adenomas (HCAs) are benign monoclonal liver tumors. Advances in molecular studies have led to the identification of distinct subtypes of HCA with unique pathways, clinical characteristics, and complication risks, underscoring the need for precise diagnosis and tailored management. Malignant transformation and bleeding remain significant concerns. Imaging plays a crucial role in the identification of these subtypes, offering a non-invasive method to guide clinical decision-making. Most studies involving patients with HCAs have been conducted in Western populations; however, the number of studies focused on Asian population has increased in recent years. HCAs exhibit distinct features in Asian population, such as a higher prevalence among male patients and specific subtypes (e.g., inflammatory HCAs). Current clinical guidelines are predominantly influenced by Western data, which may not fully capture these regional differences in epidemiology and subtype distribution. Therefore, this review presents the updated molecular classification of HCAs and their epidemiologic differences between Asian and Western populations, and discuss the role of imaging techniques, particularly magnetic resonance imaging using hepatobiliary contrast agents, in classifying the subtypes and predicting the risk of hepatocellular carcinoma.
6.Liver transplantation outcomes in patients with primary tricuspid regurgitation with coaptation defects: a retrospective analysis in a high-volume transplant center
Kyoung-Sun KIM ; Sun-Young HA ; Seong-Mi YANG ; Hye-Mee KWON ; Sung-Hoon KIM ; In-Gu JUN ; Jun-Gol SONG ; Gyu-Sam HWANG
Korean Journal of Anesthesiology 2025;78(3):261-271
Background:
Cardiovascular diseases are the leading cause of mortality after liver transplantation (LT). Although the impact of secondary tricuspid regurgitation (TR) with severe pulmonary hypertension (PH) is well investigated, the impact of primary TR with tricuspid valve incompetence (TVI) on LT outcomes remains unclear. We aimed to investigate the prevalence and impact of primary TR with TVI on LT outcomes in a large-volume LT center.
Methods:
We retrospectively examined 5 512 consecutive LT recipients who underwent routine pretransplant echocardiography between 2008 and 2020. Patients were categorized based on the presence of anatomical TVI, specifically defined by incomplete coaptation, coaptation failure, prolapse, and flail leaflets of tricuspid valve (TV). Propensity score (PS)-based inverse probability weighting (IPW) was used to balance clinical and cardiovascular risk variables. The outcomes were one-year cumulative all-cause mortality and 30-day major adverse cardiovascular events (MACE).
Results:
Anatomical TVI was identified in 14 patients (0.3%). Although rare, these patients exhibited significantly lower post-LT one-year survival rates (64.3% vs. 91.5%, P < 0.001) and higher 30-day MACE rates (42.9% vs. 16.9%, P = 0.026) than patients without TVI. They also had worse survival irrespective of echocardiographic evidence of PH (P < 0.001) and exhibited higher one-year mortality (IPW-adjusted hazard ratio: 4.09, P = 0.002) and increased 30-day MACE rates (IPW-adjusted odds ratio: 1.24, P = 0.048).
Conclusions
Primary TR with anatomical TVI was associated with significantly reduced one-year survival and increased post-LT MACE rates. These patients should be prioritized similarly to those with secondary TR with severe PH, with appropriate pretransplant evaluations and treatments to improve survival outcomes.
7.Characteristics and Prevalence of Sequelae after COVID-19: A Longitudinal Cohort Study
Se Ju LEE ; Yae Jee BAEK ; Su Hwan LEE ; Jung Ho KIM ; Jin Young AHN ; Jooyun KIM ; Ji Hoon JEON ; Hyeri SEOK ; Won Suk CHOI ; Dae Won PARK ; Yunsang CHOI ; Kyoung-Ho SONG ; Eu Suk KIM ; Hong Bin KIM ; Jae-Hoon KO ; Kyong Ran PECK ; Jae-Phil CHOI ; Jun Hyoung KIM ; Hee-Sung KIM ; Hye Won JEONG ; Jun Yong CHOI
Infection and Chemotherapy 2025;57(1):72-80
Background:
The World Health Organization has declared the end of the coronavirus disease 2019 (COVID-19) public health emergency. However, this did not indicate the end of COVID-19. Several months after the infection, numerous patients complain of respiratory or nonspecific symptoms; this condition is called long COVID. Even patients with mild COVID-19 can experience long COVID, thus the burden of long COVID remains considerable. Therefore, we conducted this study to comprehensively analyze the effects of long COVID using multi-faceted assessments.
Materials and Methods:
We conducted a prospective cohort study involving patients diagnosed with COVID-19 between February 2020 and September 2021 in six tertiary hospitals in Korea. Patients were followed up at 1, 3, 6, 12, 18, and 24 months after discharge. Long COVID was defined as the persistence of three or more COVID-19-related symptoms. The primary outcome of this study was the prevalence of long COVID after the period of COVID-19.
Results:
During the study period, 290 patients were enrolled. Among them, 54.5 and 34.6% experienced long COVID within 6 months and after more than 18 months, respectively. Several patients showed abnormal results when tested for post-traumatic stress disorder (17.4%) and anxiety (31.9%) after 18 months. In patients who underwent follow-up chest computed tomography 18 months after COVID-19, abnormal findings remained at 51.9%. Males (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.53; P=0.004) and elderly (OR, 1.04; 95% CI, 1.00–1.09; P=0.04) showed a significant association with long COVID after 12–18 months in a multivariable logistic regression analysis.
Conclusion
Many patients still showed long COVID after 18 months post SARS-CoV-2 infection. When managing these patients, the assessment of multiple aspects is necessary.
8.Comparison of SPISE and METS-IR and Other Markers to Predict Insulin Resistance and Elevated Liver Transaminases in Children and Adolescents
Kyungchul SONG ; Eunju LEE ; Hye Sun LEE ; Hana LEE ; Ji-Won LEE ; Hyun Wook CHAE ; Yu-Jin KWON
Diabetes & Metabolism Journal 2025;49(2):264-274
Background:
Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population.
Methods:
Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points.
Results:
All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point.
Conclusion
SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.
9.Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea
Jung A KIM ; Kyeong Jin KIM ; Jimi CHOI ; Kyoung Jin KIM ; Eyun SONG ; Ji Hee YU ; Nam Hoon KIM ; Hye Jin YOO ; Ji A SEO ; Nan Hee KIM ; Kyung Mook CHOI ; Sei Hyun BAIK ; Sin Gon KIM
Endocrinology and Metabolism 2025;40(1):125-134
Background:
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods:
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results:
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.
10.Association between Bioelectrical Impedance Parameters, Magnetic Resonance Imaging Muscle Parameters, and Fatty Liver Severity in Children and Adolescents
Kyungchul SONG ; Eun Gyung SEOL ; Eunju LEE ; Hye Sun LEE ; Hana LEE ; Hyun Wook CHAE ; Hyun Joo SHIN
Gut and Liver 2025;19(1):108-115
Background/Aims:
To evaluate the associations between pediatric fatty liver severity, bioelectrical impedance analysis (BIA), and magnetic resonance imaging parameters, including total psoas muscle surface area (tPMSA) and paraspinal muscle fat (PMF).
Methods:
Children and adolescents who underwent BIA and liver magnetic resonance imaging between September 2022 and November 2023 were included. Linear regression analyses identified predictors of liver proton density fat fraction (PDFF) including BIA parameters, tPMSA, and PMF. Ordinal logistic regression analysis identified the association between these parameters and fatty liver grades. Pearson’s correlation coefficients were used to evaluate the relationships between tPMSA and muscle-related BIA parameters, and between PMF and fat-related BIA parameters.
Results:
Overall, 74 participants aged 8 to 16 years were included in the study. In the linear regression analyses, the percentage of body fat was positively associated with PDFF in all participants, whereas muscle-related BIA parameters were negatively associated with PDFF in participants with obesity. PMF and the PMF index were positively associated with PDFF in normalweight and overweight participants. In the ordinal logistic regression, percentage of body fat was positively associated with fatty liver grade in normal-weight and overweight participants and those with obesity, whereas muscle-related BIA parameters were negatively associated with fatty liver grade in participants with obesity. The PMF index was positively associated with fatty liver grade in normal/overweight participants. In the Pearson correlation analysis, muscle-related BIA parameters were correlated with tPMSA, and the fat-related BIA parameters were correlated with PMF.
Conclusions
BIA parameters and PMF are potential screening tools for assessing fatty liver in children.

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