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"Soon Sun Kim"

Original Article

GAFAD: A liquid chromatography-tandem mass spectrometry-based model for early hepatocellular carcinoma detection beyond GALAD’s limitations
Hyojin Kim, Wonseok Oh, Juri Park, Saeyoung Lee, Won Suk Yang, Soon Sun Kim, Jae Youn Cheong, Je-Hyun Baek
Clin Mol Hepatol 2026;32(3):1225-1239.
Published online February 25, 2026
DOI: https://doi.org/10.3350/cmh.2025.1244
Background/Aims
The GALAD (Gender, Age, Lens culinaris agglutinin-reactive alpha-fetoprotein [AFP-L3], alpha-fetoprotein [AFP], and des-γ-carboxy prothrombin) score, widely used for hepatocellular carcinoma (HCC) detection, was primarily derived from cohorts with advanced-stage tumors and elevated biomarker levels, potentially overestimating accuracy in early-stage disease. Furthermore, the lectin-based AFP-L3 assay has poor sensitivity at low AFP concentrations, limiting detection of small or AFP-negative tumors.
Methods
We developed GAFAD, a multivariable model replacing AFP-L3 with fucosylated AFP percentage, quantified by a validated liquid chromatography–tandem mass spectrometry assay. The model was trained and tested using a hepatitis B virus (HBV)-related cohort (HCC n=235; non-HCC n=290), a diagnostically challenging set with substantial overlap in biomarker levels between HCC and non-HCC. Moreover, a final model (GAFAD) was validated in two independent cohorts (HCC n=210; non-HCC n=245), comprising HBV-, HCV-related and non-viral etiologies.
Results
In the development cohort, GAFAD showed superior diagnostic performance to GALAD for distinguishing HCC from non-HCC, with a higher area under the receiver operating characteristic curve (AUC, 0.938 vs. 0.887; P<0.0001) and greater sensitivity (82% vs. 66%) and accuracy (86% vs. 79%) at 90% specificity. In the external validation cohort, GAFAD similarly outperformed GALAD, achieving a higher AUC (0.874 vs. 0.841, P<0.05), greater sensitivity (72% vs. 57%), and improved accuracy (82% vs. 75%) at 90% specificity. This superiority extended to early-stage, very-early-stage, and AFP-negative HCC.
Conclusions
GAFAD provides a reliable and generalizable tool for early HCC detection across diverse etiologies, supporting its clinical applicability in surveillance and diagnosis.
  • 1,476 View
  • 132 Download

Correspondence

Original Article

Bacteroides eggerthii ameliorates metabolic dysfunction-associated steatotic liver disease through host–microbe signaling and highlights 2-hydroxyisocaproate as a potential effector
Jiyi Choi, Moon Gyeong Yoon, Se Ha Jang, Geum Ok Baek, Hyun Sun Jung, Na-Rae Lee, Choong Hwan Lee, Ji Eun Han, Jae Youn Cheong, Jung Woo Eun, Soon Sun Kim
Clin Mol Hepatol 2026;32(1):239-257.
Published online October 27, 2025
DOI: https://doi.org/10.3350/cmh.2025.0475
Background/Aims
Gut microbiome plays a pivotal role in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, yet, associated functional mechanisms and host responses of specific microbial species remain insufficiently characterized. This study investigated the Bacteroides eggerthii therapeutic effects on MASLD by integrating multi-omics analysis and experimental validation in a Western diet (WD)-induced mouse model.
Methods
Candidate strains were identified using 16S rRNA gene sequencing of fecal samples from individuals with and without MASLD or obesity. B. eggerthii, a species significantly depleted in both groups, was selected for functional evaluation. Male C57BL/6J mice were fed a WD or WD supplemented with B. eggerthii (WD+B) for 12 weeks. Liver histology, serum biochemistry, fecal microbiome and metabolome profiling, and hepatic and intestinal transcriptomic analyses were performed. Anti-steatotic effects of B. eggerthii–derived metabolites were validated in vitro.
Results
Bacteroides eggerthii supplementation significantly improved liver weight, inflammation, fibrosis, and steatosis in WD+B group compared to WD alone. PICRUSt-based LEfSe analysis revealed choloylglycine hydrolase activity enrichment in gut microbiota, and strain-specific qPCR confirmed colonization in mouse colon. Integrated transcriptomic analyses revealed lipid and bile acid signaling pathway restoration, including CD36, FXR, and FGF15. Untargeted metabolomics identified elevated 2-hydroxyisocaproic acid (HICA) as a strain-derived metabolite in feces and B. eggerthii culture supernatants. In vitro, HICA significantly reduced lipid accumulation in free fatty acid-induced steatosis models.
Conclusions
Bacteroides eggerthii ameliorates MASLD via gut-liver axis modulation, including bile acid metabolism and hepatic lipid signaling. These underscore its therapeutic potential and highlight HICA as a novel microbiome-derived metabolite with anti-steatotic activity.

Citations

Citations to this article as recorded by  Crossref logo
  • Letter to the Editor: Circadian and microbial misalignment in metabolic dysfunction-associated steatotic liver disease - mechanistic insights and chronotherapeutic potential
    Christos Savvidis, Ioannis Ilias
    World Journal of Experimental Medicine.2026;[Epub]     CrossRef
  • Decoding the Gut–Fat–Heart Axis: From Molecular Communication Networks to Clinical Translation Strategies
    Zijin Sun, Wei Shao, Haojia Zhang, Kai Wang, Yongchao Liu, Rui Zhou
    International Journal of Molecular Sciences.2026; 27(12): 5596.     CrossRef
  • 5,381 View
  • 456 Download
  • 2 Web of Science
  • Crossref

Reply to Correspondence

Reply to correspondence 2 on “MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation”
Ji Eun Han, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
Clin Mol Hepatol 2026;32(1):e121-e124.
Published online June 4, 2025
DOI: https://doi.org/10.3350/cmh.2025.0564
  • 3,725 View
  • 45 Download

Editorial

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to Editorial 2 on “MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation”
    Tiantian Wang, Wenjie Huang, Limin Xia
    Clinical and Molecular Hepatology.2026; 32(1): e93.     CrossRef
  • Reply to correspondence 2 on “MET promotes hepatocellular carcinoma development through the promotion of TRIB3-mediated FOXO1 degradation”
    Ji Eun Han, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
    Clinical and Molecular Hepatology.2026; 32(1): e121.     CrossRef
  • Strategic drug sequencing in hepatocellular carcinoma in the era of chemo-diversity: maximizing the therapeutic benefit of lenvatinib
    Hideki Iwamoto, Shigeo Shimose, Hironori Koga, Takumi Kawaguchi
    Journal of Liver Cancer.2026; 26(1): 83.     CrossRef
  • The role and possible mechanism of intestinal fungi in the progression of chronic liver diseases
    Yirui Hu, Ye Yang, Shuyan Wang, Huikuan Chu
    npj Biofilms and Microbiomes.2026;[Epub]     CrossRef
  • 3,803 View
  • 86 Download
  • 2 Web of Science
  • Crossref

Correspondences

Correspondence to editorial on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
Soon Sun Kim, Hyung Seok Kim, Jae Youn Cheong, Jung Woo Eun
Clin Mol Hepatol 2026;32(1):e72-e74.
Published online April 4, 2025
DOI: https://doi.org/10.3350/cmh.2025.0350

Citations

Citations to this article as recorded by  Crossref logo
  • GULP1: New hope for hepatocellular carcinoma: Reply to correspondence on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
    Yuhao Xie, Lu-Qi Cao, John Wurpel, Zhe-Sheng Chen
    Clinical and Molecular Hepatology.2026; 32(1): e112.     CrossRef
  • 2,849 View
  • 38 Download
  • Crossref
Correspondence to letter to the editor on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
Hyung Seok Kim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
Clin Mol Hepatol 2026;32(1):e103-e105.
Published online March 19, 2025
DOI: https://doi.org/10.3350/cmh.2025.0287
  • 5,862 View
  • 53 Download

Special Issue

Steatotic liver disease

KASL clinical practice guidelines for the management of metabolic dysfunction-associated steatotic liver disease 2025
Won Sohn, Young-Sun Lee, Soon Sun Kim, Jung Hee Kim, Young-Joo Jin, Gi-Ae Kim, Pil Soo Sung, Jeong-Ju Yoo, Young Chang, Eun Joo Lee, Hye Won Lee, Miyoung Choi, Su Jong Yu, Young Kul Jung, Byoung Kuk Jang, on behalf of The Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2025;31(Suppl):S1-S31.
Published online February 19, 2025
DOI: https://doi.org/10.3350/cmh.2025.0045

Citations

Citations to this article as recorded by  Crossref logo
  • Metabolic dysfunction-associated steatotic liver disease and adverse pregnancy outcomes: a nationwide cohort study
    Young Mi Jung, Taesu Kim, Min-Jeong Oh, Dong Hyeon Lee, Geum Joon Cho, Won Kim
    Hepatology International.2026; 20(1): 69.     CrossRef
  • Unmasking Kidney Risk in Steatotic Liver Disease: A Call for Metabolic Precision
    Chan-Young Jung
    Gut and Liver.2026; 20(1): 1.     CrossRef
  • Prognostic value of non-invasive fibrosis assessment scores in predicting mortality among individuals with metabolic dysfunction-associated steatotic liver disease
    Lingjie Wu, Shunling Cai, Zhongbin Lin, Ruilie Chen, Yuanfeng Zhang, Xiaobing Gong
    BMC Public Health.2026;[Epub]     CrossRef
  • Optimal screening criteria for metabolic dysfunction-associated steatotic liver disease with fibrosis
    Byeong Geun Song, Myung Ji Goh, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Dong Hyun Sinn
    Annals of Hepatology.2026; 31(2): 102199.     CrossRef
  • Managing Metabolic Dysfunction–Associated Steatotic Liver Disease: Protocol for a Scoping Review of Patient Perceptions, Barriers, and Facilitators
    Sikyeong Park, Yu Shin Park, Dahye Hong, Bada Kang
    JMIR Research Protocols.2026; 15: e81404.     CrossRef
  • Risk Stratification of Chronic Kidney Disease in Adults Using Noninvasive Fibrosis Tests Based on the American Diabetes Association Algorithm
    Chan‐Young Jung, Hye Won Lee, Jung Il Lee, Han Ah Lee, Seung Up Kim
    Diabetes, Obesity and Metabolism.2026; 28(6): 5240.     CrossRef
  • Rethinking first-line screening in MASLD beyond the limitations of Fibrosis-4 index: Editorial on “Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease”
    Han Ah Lee, Young Youn Cho, Hyung Joon Kim
    Clinical and Molecular Hepatology.2026; 32(2): 921.     CrossRef
  • Metabolic Dysfunction‐Associated Steatotic Liver Disease and Obesity: Pathogenesis, Diagnostics, Risk Stratification, and Therapeutic Approach
    Beom Kyung Kim
    The Kaohsiung Journal of Medical Sciences.2026;[Epub]     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease: On track to become the dominant etiology of hepatocellular carcinoma: Reply to correspondence on “Downregulation of the MARC1 p.A165 risk allele reduces hepatocyte lipid content by increasing beta-
    Jian Xu, Wei Zhang, Guo Wu, Jingdong Li
    Clinical and Molecular Hepatology.2026; 32(2): e257.     CrossRef
  • Current Trends and Perspectives on Obesity and Metabolic Dysfunction-Associated Steatohepatitis in East Asia
    Soo Lim, Hui Zhou, Wataru Ogawa
    Journal of Obesity & Metabolic Syndrome.2026; 35(2): 130.     CrossRef
  • Evolving B-mode ultrasound-based techniques for assessing metabolic dysfunction-associated steatotic liver disease: Now and beyond
    Walaa Abdelhamed, Mohamed Elbadry, Mohamed El-Kassas
    Liver Research.2026; 10(2): 109.     CrossRef
  • Baduanjin for Non-Alcoholic Fatty Liver Disease: A Systematic Review
    Hyo-Ju Woo, Jung-Gyung Lee, Bong-Jin Shin, Jae-Jin Han, Sun-Young Park, Eui-Hyoung Hwang
    Journal of Korean Medicine Rehabilitation.2026; 36(2): 85.     CrossRef
  • Surgically confirmed severe endometriosis is associated with lower risk of steatotic liver disease: Evidence of estrogen‐linked hepatic–reproductive crosstalk
    Jung Hyun Park, Keungmo Yang, Hyun Yang, Si Hyun Bae, Mee‐Ran Kim, Jaejun Lee
    International Journal of Gynecology & Obstetrics.2026;[Epub]     CrossRef
  • Non-Invasive Tests in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease: From Diagnosis to Treatment Monitoring
    Han Ah Lee, Young Youn Cho, Hyung Joon Kim
    Clinical Ultrasound.2026; 11(1): 1.     CrossRef
  • An Arterial‐Enhancing Liver Nodule With Washout in a Patient With Metabolic and Alcohol‐Associated Liver Disease
    Soon Kyu Lee, Sun Young Jun, Young Chul Yoon
    Journal of Gastroenterology and Hepatology.2026; 41(7): 1991.     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated alcohol-related liver disease in human immunodeficiency virus
    Dinuka Bandara, Krishan Joshi, Carol Singh, Aalam Sohal, Mohanad Al-Qaisi, Nilofar Najafian
    World Journal of Virology.2026;[Epub]     CrossRef
  • CT attenuation–based hepatic steatosis assessment using 3D organ segmentation: Impact of tube voltage and need for cutoff adjustment
    Jeongin Yoo, Ijin Joo, Sun Kyung Jeon, Junghoan Park, Jeong Min Lee
    European Journal of Radiology.2026; 203: 113021.     CrossRef
  • Alcohol consumption and dementia risk in steatotic liver disease: a nationwide cohort study
    Ji Won Han, Seunghee Na, Kyungdo Han, Kyu Na Lee, Do Young Kim, Sang Hoon Ahn, Mi Na Kim
    Hepatology International.2026;[Epub]     CrossRef
  • Pharmacological treatment of metabolic dysfunction–associated steatotic liver disease: a narrative review
    Jeong-Hwan Lee, Jeong-Ju Yoo, Sang Gyune Kim, Young Seok Kim
    Journal of the Korean Medical Association.2026; 69(6): 492.     CrossRef
  • Differential Infiltration of T-Cell Populations in Tumor and Liver Tissues Predicts Recurrence-Free Survival in Surgically Resected Hepatocellular Carcinoma
    Eun Ji Jang, Ho Joong Choi, Young Kyoung You, Deok Hwa Seo, Mi Hyun Kwon, Keungmo Yang, Jaejun Lee, Jeong Won Jang, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
    Cancers.2025; 17(9): 1548.     CrossRef
  • Metabolic Dysfunction-Associated Steatotic Liver Disease, Recent Revision of Terminology and Its Implications
    Hyo Young Lee, Eileen L. Yoon
    The Korean Journal of Gastroenterology.2025; 85(2): 126.     CrossRef
  • Advances in identifying risk factors of metabolic dysfunction-associated alcohol-related liver disease
    Rui-Qi Ye, Yi-Fan Chen, Chang Ma, Xi Cheng, Wei Guo, Sha Li
    Biomedicine & Pharmacotherapy.2025; 188: 118191.     CrossRef
  • A Case Report of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) with Improved Cardiometabolic Risk Factors Following Treatment with Saenggangunbi-tang
    Eun Kyung Lee, Min Jeong Park, Youngchul Kim, Jang-Hoon Lee
    The Journal of Internal Korean Medicine.2025; 46(2): 303.     CrossRef
  • Food Nutrients and Bioactive Compounds for Managing Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review
    Erdenetsogt Dungubat, Kohei Fujikura, Masahiko Kuroda, Toshio Fukusato, Yoshihisa Takahashi
    Nutrients.2025; 17(13): 2211.     CrossRef
  • Associations between steatotic liver disease subtypes and incident atrial fibrillation in young adults: a nationwide cohort study
    Jeayeon Park, Goh Eun Chung, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Eun Ju Cho
    Cardiovascular Diabetology.2025;[Epub]     CrossRef
  • Second-line antidiabetic drugs: friend or foe of the liver
    Jiwon Yang, Gunho Kim, Ju Hyun Shim, Jihyun An
    Journal of Liver Cancer.2025; 25(2): 187.     CrossRef
  • Extrahepatic manifestation of metabolic dysfunction-associated steatotic liver disease
    Anoushka Shenoy, Aijaz Ahmed, Donghee Kim
    Metabolism and Target Organ Damage.2025;[Epub]     CrossRef
  • 2025 Clinical Practice Guidelines for Diabetes: Management of Metabolic Dysfunction-Associated Steatotic Liver Disease
    Jaehyun Bae
    The Journal of Korean Diabetes.2025; 26(3): 172.     CrossRef
  • Paired snRNA-seq and scRNA-seq analysis of MASLD patients to identify early-stage markers for disease progression
    Suebin Park, Su-Hyeon Lee, Se-eun Han, Beom Kyung Kim, Byungjin Hwang
    Hepatology Communications.2025;[Epub]     CrossRef
  • Sex Hormones and Metabolic Dysfunction-Associated Steatotic Liver Disease
    Ralf Weiskirchen, Amedeo Lonardo
    International Journal of Molecular Sciences.2025; 26(19): 9594.     CrossRef
  • Discovery of ultrasound-derived fat fraction as a non-invasive tool for MASLD diagnosis
    Huiru Jin, Mengfan Jiao, Chengxiao Yu, Tingting Ren, Qingling Chen, Zixing Dai, Erfu Xie, Longfeng Jiang, Yuwen Li
    European Journal of Medical Research.2025;[Epub]     CrossRef
  • Risk of Esophageal and Gastric Cancer by Histologic Subtype in Steatotic Liver Disease: A UK Biobank Study
    Donghoon Kang, Ji Won Han, Kenneth R. Muir, Artitaya Lophatananon, Jongin Lee
    Cancers.2025; 17(21): 3416.     CrossRef
  • Implication of the Androgen Receptor in Muscle–Liver Crosstalk: An Overlooked Mechanistic Link in Lean-MASLD
    Eleni Myrto Trifylli, Christiana Charalambous, Nikolaos Spiliotopoulos, Nikolaos Papadopoulos, Anastasia Oikonomou, Spilios Manolakopoulos, Melanie Deutsch
    Livers.2025; 5(4): 65.     CrossRef
  • Time-updated FIB-4 index predicts coronary artery calcification progression in individuals with metabolic dysfunction–associated steatotic liver disease
    Yesung Lee, Woncheol Lee
    Scientific Reports.2025;[Epub]     CrossRef
  • 17,945 View
  • 445 Download
  • 28 Web of Science
  • Crossref

Original Article

GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma
Hyung Seok Kim, Jung Hwan Yoon, Ji Yi Choi, Moon Gyeong Yoon, Geum Ok Baek, Minji Kang, Se Ha Jang, Won Park, Yunjin Go, Jestlin Tianthing Ng, Suk Woo Nam, Jee-Yeong Jeong, Ji Eun Han, Hyo Jung Cho, Su Bin Lim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
Clin Mol Hepatol 2025;31(3):914-934.
Published online February 6, 2025
DOI: https://doi.org/10.3350/cmh.2024.1038
Background/Aims
Hepatocellular carcinoma (HCC) is characterized by high recurrence and mortality, necessitating the identification of reliable biomarkers. In this study, we aimed to identify the predictive gene signatures for HCC recurrence and evaluate the efficiency of GULP PTB domain-containing engulfment adaptor 1 (GULP1) as a predictive and diagnostic marker and therapeutic target for HCC.
Methods
We analyzed genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases via least absolute shrinkage and selection operator Cox regression and 10-fold cross-validation, leading to the development of a 15-gene risk score model, which was validated using three independent datasets. Serum GULP1 and α-fetoprotein levels were assessed to determine the diagnostic accuracy of the model. Using clinical cohorts and patient sera, GULP1 roles were examined, and functional assays in vitro and in vivo were used to evaluate its effects on cell growth, epithelial–mesenchymal transition (EMT), ADP-ribosylation factor 6 (ARF6) activation, and β-catenin signaling.
Results
Our newly developed risk-score model accurately predicted recurrent HCC in all datasets. Among the 15 genes in the risk score model, GULP1 was overexpressed in patients with HCC and independently predicted HCC recurrence. Its expression modulation influenced cell growth and EMT, with observed effects on ARF6 activation and β-catenin signaling pathways.
Conclusions
GULP1 is a crucial biomarker for HCC, serving as a non-invasive diagnostic and predictive tool. It also plays key roles in HCC progression. Our findings highlight the potential use of GULP1 in treatment strategies targeting EMT and HCC recurrence to improve the personalized care and patient outcomes.

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to letter to the editor on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
    Hyung Seok Kim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
    Clinical and Molecular Hepatology.2026; 32(1): e103.     CrossRef
  • GULP1, a multifaceted diagnostic biomarker and potential therapeutic target in hepatocellular carcinoma: Editorial on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
    Yuhao Xie, Lu-Qi Cao, John Wurpel, Zhe-Sheng Chen
    Clinical and Molecular Hepatology.2026; 32(1): 413.     CrossRef
  • Letter to the editor on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
    Juan Yang, Xinyi Li, Sheng Zheng
    Clinical and Molecular Hepatology.2026; 32(1): e10.     CrossRef
  • GULP1: New hope for hepatocellular carcinoma: Reply to correspondence on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
    Yuhao Xie, Lu-Qi Cao, John Wurpel, Zhe-Sheng Chen
    Clinical and Molecular Hepatology.2026; 32(1): e112.     CrossRef
  • Correspondence to editorial on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
    Soon Sun Kim, Hyung Seok Kim, Jae Youn Cheong, Jung Woo Eun
    Clinical and Molecular Hepatology.2026; 32(1): e72.     CrossRef
  • Unveiling GULP1 as a hepatocyte-specific role for recurrence: Editorial on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
    Pengde Lu, Ning Wang
    Clinical and Molecular Hepatology.2026; 32(1): 410.     CrossRef
  • Identifying Immunological Biomarkers for Major Depressive Disorder: Insights From Machine Learning, Single‐Nucleus Bioinformatics, and Experimental Validation
    Long Kangsheng, Yang Xiaohui, Pei Xin, Ye Yong, Li Hongliang, Deng Yihui, Poorani Gurumallesh Prabu
    BioMed Research International.2026;[Epub]     CrossRef
  • MASLD and MASLD-associated HCC: emerging biomarkers and therapeutic avenues
    Suki Ha, Xiang Zhang, Lanjuan Li, Jun Yu
    Science Bulletin.2026; 71(11): 2916.     CrossRef
  • The evolving landscape of biomarkers for systemic therapy in advanced hepatocellular carcinoma
    Xinyu Guo, Zhongwei Zhao, Lingyi Zhu, Shuang Liu, Lingling Zhou, Fazong Wu, Shiji Fang, Minjiang Chen, Liyun Zheng, Jiansong Ji
    Biomarker Research.2025;[Epub]     CrossRef
  • Advances in research regarding epithelial-mesenchymal transition and prostate cancer
    Xi Wei, Rui Liu, Wei Li, Qi Yu, Qing Tao Yang, Tao Li
    Frontiers in Cell and Developmental Biology.2025;[Epub]     CrossRef
  • Serum Proteomic Profile Based on the TGF‐β Pathway Stratifies Risk of Hepatocellular Carcinoma
    Xiyan Xiang, Kirti Shetty, Herbert Yu, Bibhuti Mishra, Linda L. Wong, Xianghong Jasmine Zhou, Sanjaya K. Satapathy, James M. Crawford, Patricia S. Latham, Steven‐Huy Han, Brandon Mathew, Nabil N. Dagher, Lawrence Lau, Fellanza Cacaj, Anil K. Vegesna, Srin
    Liver International.2025;[Epub]     CrossRef
  • Systematic analysis of the expression profiles and prognostic values of the FAM72 family in liver cancer
    Weihao Kong, Long Teng, Kangjie Zhang, Yajun Zou, Xingyu Wang, Jianlin Zhang
    Biochemistry and Biophysics Reports.2025; 44: 102358.     CrossRef
  • 16,189 View
  • 1,074 Download
  • 13 Web of Science
  • Crossref

Editorial

Original Article

Hepatic neoplasm

Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma
Jiwon Hong, Jung Woo Eun, Geum Ok Baek, Jae Youn Cheong, Seryoung Park, Soon Sun Kim, Hyo Jung Cho, Su Bin Lim
Clin Mol Hepatol 2024;30(3):360-374.
Published online March 15, 2024
DOI: https://doi.org/10.3350/cmh.2024.0042
Background/Aims
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers.
Methods
We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses.
Results
Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types.
Conclusions
Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.

Citations

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  • Carbonic anhydrase 9 as a circulating biomarker and therapeutic target in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab
    Yu Sato, Takahiro Kodama, Kazuki Maesaka, Machiko Kai, Kazuhiro Murai, Yuki Tahata, Yoshinobu Saito, Tasuku Nakabori, Kazuyoshi Ohkawa, Satoshi Tanaka, Ryotaro Sakamori, Masanori Miyazaki, Kunimaro Furuta, Hisashi Ishida, Kengo Matsumoto, Seiichi Tawara,
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    Shayesteh Shakarami, Nisreen M. Saleh, Farshad Zare, Raed Fanoukh-Aboqader-Al-Aouadi, Nemat Allaberdiyev, Tulkin Buzrukov, Natrayan Lakshmaiya, Ibadulla Abdullaev, Mehrdad Nourizadeh
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    3 Biotech.2025;[Epub]     CrossRef
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    Yun Seon Im, Seol Whan Oh, Ki Hoon Kim, Wona Choi, In Young Choi
    BMC Medical Informatics and Decision Making.2025;[Epub]     CrossRef
  • Harnessing plasma transcriptomics for non-invasive cancer biomarker identification: a comprehensive review
    Nur Mazidah Haji Noor Mohamed, Nurulisa Zulkifle, Siti Razila Abdul Razak
    Discover Oncology.2025;[Epub]     CrossRef
  • Unveiling etiology-specific blood biomarkers in hepatocellular carcinoma: A gateway to personalized medicine: Editorial on “Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma”
    Joseph C. Ahn, Ju Dong Yang
    Clinical and Molecular Hepatology.2024; 30(4): 689.     CrossRef
  • Technology and Future of Multi-Cancer Early Detection
    Danny A. Milner, Jochen K. Lennerz
    Life.2024; 14(7): 833.     CrossRef
  • Correspondence to editorial on “Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma”
    Su Bin Lim, Hyo Jung Cho
    Clinical and Molecular Hepatology.2024; 30(4): 1009.     CrossRef
  • 11,535 View
  • 429 Download
  • 7 Web of Science
  • Crossref

Editorial

Citations

Citations to this article as recorded by  Crossref logo
  • Association of four insulin resistance indices with liver‐related adverse outcomes: A prospective cohort study
    Xiao‐Meng Wang, Hao Yan, Wen‐Fang Zhong, Jia‐Hao Xie, Huan Chen, Jun‐Jie Wang, Wei‐Qi Song, Dong Shen, Pei‐Dong Zhang, Xi‐Ru Zhang, Jiao‐Jiao Ren, Dan Liu, Zhi‐Hao Li, Chen Mao
    Diabetes, Obesity and Metabolism.2026; 28(5): 3598.     CrossRef
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Letter to the Editor

Forms of cholangitis to be considered after SARS-CoV-2 infection
Ju-Yeon Cho, Young-Sun Lee, Soon Sun Kim, Do Seon Song, Jeong-Hoon Lee, Ji Hoon Kim
Clin Mol Hepatol 2022;28(4):929-930.
Published online September 8, 2022
DOI: https://doi.org/10.3350/cmh.2022.0260

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Original Article

Hepatic neoplasm

Hepatocellular carcinoma incidence is decreasing in Korea but increasing in the very elderly
Young Eun Chon, Seong Yong Park, Han Pyo Hong, Donghee Son, Jonghyun Lee, Eileen Yoon, Soon Sun Kim, Sang Bong Ahn, Soung Won Jeong, Dae Won Jun
Clin Mol Hepatol 2023;29(1):120-134.
Published online August 12, 2022
DOI: https://doi.org/10.3350/cmh.2021.0395
Background/Aims
A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028.
Methods
Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC.
Results
The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P<0.001). The estimated CR (17.9 per 100,000 person-years) and ASR (9.7 per 100,000 person-years) of HCC incidence in 2028 was declined, but the number of HCC patients aged ≥80 years in 2028 will be quadruple greater than the number of HCC patients in 2008 (from 521 to 2,055), comprising 21.3% of all HCC patients in 2028.
Conclusions
The ASRs of HCC in Korea have gradually declined over the past 10 years, but the number, CR, and ASR are increasing in patients aged ≥80 years.

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Special Topics

COVID-19

Update on liver disease management during the pandemic of coronavirus disease 2019 (COVID-19): 2021 KASL guideline
Ju-Yeon Cho, Young-Sun Lee, Soon Sun Kim, Do Seon Song, Jeong-Hoon Lee, Ji Hoon Kim, on behalf of the Korean Association for the Study of the Liver
Clin Mol Hepatol 2021;27(4):515-523.
Published online September 17, 2021
DOI: https://doi.org/10.3350/cmh.2021.0293

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COVID-19

Management of liver diseases during the pandemic of coronavirus disease-19
Ju-Yeon Cho, Soon Sun Kim, Young-Sun Lee, Do Seon Song, Jeong-Hoon Lee, Ji Hoon Kim, Korean Association for the Study of the Liver
Clin Mol Hepatol 2020;26(3):243-250.
Published online June 23, 2020
DOI: https://doi.org/10.3350/cmh.2020.0111

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Original Articles

Viral hepatitis

Impact of prior lamivudine use on the antiviral efficacy and development of resistance to entecavir in chronic hepatitis B patients
Joo An Hwang, Kee Bum Kim, Min Jae Yang, Sun Gyo Lim, Jae Chul Hwang, Jae Youn Cheong, Sung Won Cho, Soon Sun Kim
Clin Mol Hepatol 2015;21(2):131-140.
Published online June 26, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.2.131
Background/Aims

To determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naïve chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance.

Methods

We retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naïve patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance.

Results

Genotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naïve group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance.

Conclusions

ETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.

Citations

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  • A five years study of antiviral effect of entecavir in Chinese chronic hepatitis B patients
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  • 2 Web of Science
  • Crossref

Viral hepatitis

Serum transferrin as a liver fibrosis biomarker in patients with chronic hepatitis B
Hyo Jung Cho, Soon Sun Kim, Seun Joo Ahn, Joo Han Park, Dong Joon Kim, Young Bae Kim, Sung Won Cho, Jae Youn Cheong
Clin Mol Hepatol 2014;20(4):347-354.
Published online December 24, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.4.347
Background/Aims

Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B.

Methods

The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared.

Results

Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B.

Conclusions

Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.

Citations

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    Geneviève McCluskey, Hortense Maynadié, Delphine Borgel, Laurent Frenzel, Annie Harroche, Elsa Bianchini, Stephanie Roullet, Olivier D. Christophe, Cecile V. Denis, Caterina Casari, Peter J. Lenting
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    Weiwei Fang, Chang Pang, Xiying Li
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    Joana Ferreira, Manuel Bicho, Paula Faustino, Fátima Serejo
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    Min-Jun Liao, Jun Li, Wei Dang, Dong-Bo Chen, Wan-Ying Qin, Pu Chen, Bi-Geng Zhao, Li-Ying Ren, Ting-Feng Xu, Hong-Song Chen, Wei-Jia Liao
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    Hideki Tatsukawa, Taishu Takeuchi, Yoshiki Shinoda, Kiyotaka Hitomi
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    Seyma Katrinli, Kamil Ozdil, Abdurrahman Sahin, Oguzhan Ozturk, Gozde Kir, Ahmet Tarik Baykal, Emel Akgun, Omer Sinan Sarac, Mehmet Sokmen, H. Levent Doğanay, Gizem Dinler Doğanay
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    Hiroto Kayashima, Takashi Maeda, Noboru Harada, Takanobu Masuda, Atsushi Guntani, Shuhei Ito, Ayumi Matsuyama, Motohiro Hamatake, Shinichi Tsutsui, Hiroyuki Matsuda, Teruyoshi Ishida
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    Yoav Lurie
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Liver fibrosis, cirrhosis, and portal hypertension

Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data
Hyung Ki Kim, Yoon Jun Kim, Woo Jin Chung, Soon Sun Kim, Jae Jun Shim, Moon Seok Choi, Do Young Kim, Dae Won Jun, Soon Ho Um, Sung Jae Park, Hyun Young Woo, Young Kul Jung, Soon Koo Baik, Moon Young Kim, Soo Young Park, Jae Myeong Lee, Young Seok Kim
Clin Mol Hepatol 2014;20(1):18-27.
Published online March 26, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.1.18
Background/Aims

This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.

Methods

Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals.

Results

Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality.

Conclusions

A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.

Citations

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    Chengjian Wu, Zhaoyan Gao, Yi Shen, Guofeng Liu, Xiaoze Wang, Xuefeng Luo
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    Christophe Bureau, Hélène Larrue, Miriam Cortes-Cerisuleo, Roberto Miraglia, Bogdan Procopet, Marika Rudler, Jonel Trebicka, Lisa B. VanWagner, Virginia Hernandez-Gea
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  • Management of inadvertent puncture of the hepatic capsule accompanied by post-TIPS hemoperitoneum secondary to bleeding diathesis
    Shivam Khatri, Geovanna Erazo Villegas, Matthew Smith
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    Paula M. Novelli, Philip D. Orons
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    Andres F. Carrion, Paul Martin
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    Justin Richard Boike, Nikhilesh Ray Mazumder, Kanti Pallav Kolli, Jin Ge, Margarita German, Nathaniel Jest, Giuseppe Morelli, Erin Spengler, Adnan Said, Jennifer C. Lai, Archita P. Desai, Thomas Couri, Sonali Paul, Catherine Frenette, Elizabeth C. Verna,
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    Spela Korsic, Borut Stabuc, Pavel Skok, Peter Popovic
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    Ammar Sarwar, Jeffrey L. Weinstein, Victor Novack, Nihara Chakrala, Elliot B. Tapper, Raza Malik, Muneeb Ahmed
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  • ULTRAGARSINIO TYRIMO REIKŠMĖ VERTINANT TRANSJUGULINIO INTRAHEPATINIO PORTOSISTEMINIO ŠUNTO (TIPS) PROCEDŪROS VEIKSMINGUMĄ IR KOMPLIKACIJŲ RIZIKĄ PO PROCEDŪROS
    Dalia Mitraitė, Paula Zibalytė, Erikas Strupeikis, Sigita Gelman
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Viral hepatitis

Durability after discontinuation of nucleos(t)ide therapy in chronic HBeAg negative hepatitis patients
Young Jip Kim, Kichan Kim, Sun Hyuk Hwang, Soon Sun Kim, Dami Lee, Jae Youn Cheong, Sung Won Cho
Clin Mol Hepatol 2013;19(3):300-304.
Published online September 30, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.3.300
Background/Aims

Relapse has been reported after stopping nucleos(t)ide (NUC) therapy in the majority of chronic HBeAg negative hepatitis patients. However, the ideal treatment duration of HBeAg negative chronic hepatitis B (CHB) is not well known. We investigated the frequency of relapse in HBeAg negative CHB patients receiving NUC therapy.

Methods

The NUC therapy was discontinued at least 3 times undetectable level of HBV DNA leave 6 months space in 45 patients. Clinical relapse was defined as HBV DNA >2,000 IU/mL and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times of upper limit of normal range. Virological relapse was defined as HBV DNA >2,000 IU/mL.

Results

Clinical relapse developed in 16 (35.6%) and 24 (53.3%) patients after stopping therapy at 6 months and 12 months off therapy, respectively. Virological relapse developed 22 (48.9%) and 33 (73.3%) patients at 6 months and 12 months off therapy. The factors such as age, gender, cirrhosis, baseline AST, ALT, HBV DNA levels, treatment duration, and consolidation duration were analyzed to investigate the predictive factors associated with 1 year sustained response. Of these factors, cirrhosis (86.1% in CHB, 22.2% in LC) was significantly associated with 1 year virological relapse rate. Baseline HBV DNA and total treatment duration tended to be associated with virological relapse.

Conclusions

Virological relapse developed in the majority (73.3%) of HBeAg negative CHB patients and clinical relapse developed in the half (53.3%) of patients at 1 year off therapy. Cirrhosis may be associated with the low rate of virological relapse.

Citations

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    Florian van Bömmel, Thomas Berg
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    Apichat Kaewdech, Pimsiri Sripongpun
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Viral hepatitis

Association between apolipoprotein E genotype, chronic liver disease, and hepatitis B virus
Seun Joo Ahn, Dong Kyu Kim, Soon Sun Kim, Chang Bum Bae, Hyo Jung Cho, Han Gyeol Kim, Young Jip Kim, Joo Ho Lee, Hyo Jin Lee, Mi Yeon Lee, Kee Bum Kim, Jin Hee Cho, Sung Won Cho, Jae Youn Cheong
Korean J Hepatol 2012;18(3):295-301.
Published online September 25, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.3.295
Background/Aims

Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies.

Methods

This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits.

Results

The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype.

Conclusions

The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.

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