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Correspondence

Reply to correspondence on “Beyond the Single Model: Critical Considerations for Translating HCC Triplet Immunotherapy from Bench to Bedside.”
Hideki Iwamoto, Hironori Koga, Takumi Kawaguchi
Received January 7, 2026  Accepted January 17, 2026  Published online January 27, 2026  
DOI: https://doi.org/10.3350/cmh.2026.0023    [Accepted]
  • 703 View
  • 21 Download

Review

Clinical applications of immunogenomics in hepatocellular carcinoma
James K. Carter, Daniel C. Cameron, Augusto Villanueva
Clin Mol Hepatol 2026;32(2):511-535.
Published online January 6, 2026
DOI: https://doi.org/10.3350/cmh.2025.1323
Liver cancer is one of the deadliest malignancies, with increasing incidence worldwide. Recent advances in immunotherapy have expanded the options for systemic therapy against advanced hepatocellular carcinoma (HCC), but there are no biomarkers currently available to predict which patients will respond, leading to suboptimal patient selection strategies. Understanding of the genetic and immunologic features of HCC is accelerating rapidly through the use of single cell and spatial transcriptomic techniques. However, there is a need to translate insights gained through these new studies to improve treatment options and improve patient selection. In this review we summarize knowledge of the immunogenomics of HCC, emphasizing recent advances, and discuss progress toward clinical translation.

Citations

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  • Association of NUDT1 expression with the clinical outcomes of primary hepatocellular carcinoma
    Yingda Xie, Xiaochen Ding, Fuqiang Ma
    Asian Journal of Surgery.2026;[Epub]     CrossRef
  • 1,484 View
  • 123 Download
  • Crossref

Research Letter

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  • Engineering the future of precision cancer immunotherapy: Integrating neoantigen biology, engineered delivery platforms, and clinical translation.
    Muhammad Kamran Khan, M. Imad Khan Khalil, Yunjing Zhuo, Hao Liu, Jiahao Gu, Shiming Wang, Imam Hussain, Yang Liu, Yaseen Hussain, Rashid Khan, Zhenbo Tong, Zahid Hussain, Majid Ali, Muhammad Umar, Salim Ullah, Fu-Gen Wu, Hongtao Xu
    Materials Today Advances.2026; 30: 100808.     CrossRef
  • 1,895 View
  • 162 Download
  • 1 Web of Science
  • Crossref

Review

Tumor-based biomarkers and circulating tumor DNA for precision medicine in advanced hepatocellular carcinoma
Sabrina Sidali, Claudia Campani, Jihyun An, Ju Hyun Shim, Jean-Charles Nault
Clin Mol Hepatol 2026;32(1):69-90.
Published online August 20, 2025
DOI: https://doi.org/10.3350/cmh.2025.0746
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and remains a major cause of cancer-related mortality worldwide. Systemic therapies, including targeted therapies and immune checkpoint inhibitors, have revolutionized the management of advanced HCC. Although the prognosis of patients with advanced HCC remains poor, significant progress has been made with recent advances in drug development, particularly with the introduction of effective treatments such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab. Indeed, treatment response varies significantly among patients, highlighting the need for robust biomarkers. In addition, the development of molecular driver-targeted therapies remains an active research focus as most genetic alterations observed in HCC are currently undruggable. Meeting these goals will require additional efforts to obtain histological material in clinical trials, in order to enable robust translational research. This review explores the current landscape of biomarkers of response to systemic treatments in HCC, including molecular, immune-based markers as well as circulating tumor DNA and highlights potential paths of improvement.

Citations

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  • A novel signature of palmitoylation for predicting prognosis and therapeutic response of hepatocellular carcinoma
    Yun Li, Zhongquan Yi, Linhua Liu, Danping Huang
    Discover Oncology.2026;[Epub]     CrossRef
  • Tislelizumab-induced hyperosmolar diabetic ketoacidosis complicated with rhabdomyolysis in hepatocellular carcinoma patients: case report
    Longjun Chen, Xiaojuan Zeng, Tianping Li
    Frontiers in Oncology.2026;[Epub]     CrossRef
  • Functional Interpretation of Recurrent Genetic Variants in Hepatocellular Carcinoma: Molecular Consequences and Clinical Relevance
    Yuntao Ye, Zhulin Xu, Jiang Wang, Chunyu Chen, Yuan Peng, Bo Li, Shaoqiu Chen
    Human Mutation.2026;[Epub]     CrossRef
  • Prognostic value of tumor microenvironment-based molecular subtypes in hepatocellular carcinoma patients undergoing surgery for spinal metastases: refining conventional scoring systems
    Bing Liang, Annan Hu, Jian Zhou, Juan Li, Jian Dong
    Clinical and Experimental Medicine.2025;[Epub]     CrossRef
  • 6,638 View
  • 226 Download
  • 5 Web of Science
  • Crossref

Correspondence

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  • Reply to correspondence on “Molecular classification of hepatocellular carcinoma based on zoned metabolic feature and oncogenic signaling pathway”
    Eun Ji Jang, Pil Soo Sung
    Clinical and Molecular Hepatology.2026; 32(1): e115.     CrossRef
  • Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography: A Potential Imaging Biomarker for Predicting Response to Combination Immunotherapy in Hepatocellular Carcinoma
    Masatoshi Kudo
    Liver Cancer.2025; 14(5): 511.     CrossRef
  • 5,569 View
  • 38 Download
  • Crossref

Editorials

Citations

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  • Correspondence to editorial on “CD36 Promotes iron accumulation and dysfunction in CD8+ T cells via the p38-CEBPB-TfR1 axis in early-stage hepatocellular carcinoma”
    Yifei Qin, Peng Lin, Huijie Bian, Zhi-Nan Chen, Jiao Wu
    Clinical and Molecular Hepatology.2026; 32(1): e75.     CrossRef
  • Reprogrammed Lipid Metabolism as a Gatekeeper of Hepatocarcinogenesis: from Enzyme Regulation to Precision Therapy
    Luxi Yang, Jing Yang, Zhonghong Xiong, Jinsen Wei, Xiaojuan Jiang, Huili Ye, Yumin Li
    Current Oncology Reports.2026;[Epub]     CrossRef
  • 4,334 View
  • 91 Download
  • 1 Web of Science
  • Crossref

Hepatic neoplasm

Citations

Citations to this article as recorded by  Crossref logo
  • Distinct tumor immune microenvironment modulation by anti-PD-1/PD-L1, VEGF, and CTLA-4 blockade provides a rationale for triplet therapy in hepatocellular carcinoma
    Hideki Iwamoto, Hironori Koga, Takumi Kawaguchi
    Clinical and Molecular Hepatology.2026; 32(1): e38.     CrossRef
  • Correspondence to editorial on “Integrated molecular characterization of sarcomatoid hepatocellular carcinoma”
    Rong-Qi Sun, Shao-Lai Zhou
    Clinical and Molecular Hepatology.2025; 31(2): e192.     CrossRef
  • Curative response to combined targeted-immunotherapy for post-hepatectomy lymph node metastasis in sarcomatoid hepatocellular carcinoma: case report and literature review
    Pan Liu, Song Zhang, Xiao-Ming Xin, Min Jing, Lie-Dong Wen, Xin Xiang, Shun-Hai Liu
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • 7,643 View
  • 41 Download
  • 3 Web of Science
  • Crossref

Review

Hepatic neoplasm

Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang Li, Chujun Cai, Chendong Wang, Xiaoping Chen, Bixiang Zhang, Zhao Huang
Clin Mol Hepatol 2025;31(2):350-381.
Published online December 11, 2024
DOI: https://doi.org/10.3350/cmh.2024.0857
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

Citations

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  • Probiotic-Derived Strain-Specific Metabolites Ameliorate Metabolic Dysfunction–Associated Steatotic Liver Disease through Modulation of the Gut-Liver Axis
    Sang Jun Yoon, Jieun Choi, Sung-Min Won, Jeong Seok Yu, Hee Young Kim, Hyun Chae Joung, In Gyu Park, Jung A Eom, Sang Hak Han, Do Yup Lee, Ki Tae Suk
    Probiotics and Antimicrobial Proteins.2026; 18(3): 4353.     CrossRef
  • Global research trends in bacteriophage and gut microbiota: a bibliometric and visual analysis from 2012 to 2025
    Hui-Fang Kuang, Xiong-Yilang Jiang, Song-Yan Tie, Kun Lian, Mu-Yi Hao, Hang Xu, Xiao Huang, Yi Yang, Qian Guo, Jie Li, Ling-Li Chen
    Frontiers in Microbiology.2026;[Epub]     CrossRef
  • Cinobufagin as a Potential Intervention Against Liver Cancer—A Comprehensive Review
    Nicole Simone de Lima Coelho, Victória Dogani Rodrigues, Otávio Simões Girotto, Renato César Moretti Júnior, Vítor Engrácia Valenti, Maria Angélica Miglino, Mônica Duarte da Silva, Caio Sérgio Galina Spilla, Ana Luiza Decanini Miranda de Souza, Sandra Mar
    Pharmaceuticals.2026; 19(1): 158.     CrossRef
  • Gut microbial signatures of advanced hepatocellular carcinoma and their potential diagnostic value
    Yan Wang, Zhen Yang, Chuang Liu, Yufeng Liu, Zhongyuan Bai, Wentao Miao, Tiantian Zhang, Yan Wang, Xiang Li, Zhiyong Lai, Jun Xu
    Frontiers in Microbiology.2026;[Epub]     CrossRef
  • Exploratory Analysis of Gut Microbiome and Metabolic Profile Changes Following Lenvatinib and Anti-PD-1 Combination Therapy in Liver Cancer
    Rui Zhong, Zhikun Lin, Binghui Jin, Xiaolin Wang, Hua Mu, Jinlong Hu, Qi Li, Peng Dou, Xinyu Liu, Chunxiu Hu, Guowang Xu, Guang Tan
    Metabolites.2026; 16(2): 97.     CrossRef
  • Epistemic compression in large language model explanations of the gut–liver axis
    Man Sun, Dan Zang, Huan Zhou, Yi-Lin Che, Jun Chen
    Frontiers in Cellular and Infection Microbiology.2026;[Epub]     CrossRef
  • Gut microbiota-mediated oncogenesis in hepatocellular carcinoma: a new avenue for therapeutic intervention
    Aswathi Ramesh, Rajasekaran Subbarayan, Dhasarathdev Srinivasan, Ranjith Balakrishnan, Rupendra Shrestha, Ankush Chauhan
    International Journal of Surgery.2026; 112(2): 4725.     CrossRef
  • Normal weight obesity and the risk of liver cancer in 0.3 million Chinese adults: a prospective multicenter cohort study
    Chun-Rui Wang, Wei-Hong Huang, Zhang-You Guo, Chen-Wei Tang, Xin Dai, Ling-Xiang Xu, Guo-Chao Zhong
    International Journal of Surgery.2026; 112(2): 3530.     CrossRef
  • The intratumoral microbiome in colorectal cancer: origins, microenvironmental interactions, and new horizons in precision medicine
    Xuemei Li, Qian Wang, Qiang Yuan, Li Wang
    Frontiers in Immunology.2026;[Epub]     CrossRef
  • Effects of tacrolimus treatment on the gut microbiota and metabolites in liver transplant recipients
    Guohui Wang, Lu Liu, Hanshu Zhang, Panpan Mao, Saijuan Lu, Xiaofang Zhang, Xingde Li, Cangsang Song, Nikhilesh Anand
    PLOS One.2026; 21(2): e0343817.     CrossRef
  • The Polyphenol–Microbiota Axis: Molecular Mechanisms, Metabolic Pathways, and Therapeutic Perspectives in Human Health
    Andrea Ballini, Simona Nicole Barile, Alfredo De Rosa, Maria Eleonora Bizzoca, Mariarosaria Boccellino, Salvatore Scacco, Stefania Cantore, Lorenzo Lo Muzio, Francesco Massimo Lasorsa, Roberto Arrigoni
    Journal of Personalized Medicine.2026; 16(3): 142.     CrossRef
  • Intestinal-hepatic axis-mediated hepatocarcinogenesis and traditional Chinese medicine intervention strategies
    Lulu Song, Ying Zhou, Zhajun Zhan, Libin Pan, Luo Fang
    Pharmacological Research - Modern Chinese Medicine.2026; 19: 100790.     CrossRef
  • Associations among physical activity, diet, non-lifestyle characteristics and the gut microbiome of cancer patients: A scoping review and network analysis
    Jerry Armah, Sarah Alzahid, Qinglin Pei, Lakeshia Cousin, Dany Fanfan, Coy Heldermon, Debra Lyon
    Oncoscience.2026; 13: 85.     CrossRef
  • Microbiome and metabolite signatures for cirrhosis to HCC risk stratification: progress, controversies, and gaps
    Yanan Duan, Mengting Yang, Miaomiao Li, Yu Sun, Shiguo Liu
    Frontiers in Cellular and Infection Microbiology.2026;[Epub]     CrossRef
  • Mucosal immunity in cancer metastasis: roles, mechanisms, and therapeutic implications
    Yaru Miao, Dongdong Cui, Yanghui Bi, Ruiping Zhang
    Frontiers in Immunology.2026;[Epub]     CrossRef
  • Harnessing the gut microbiota in extra-intestinal cancers: from causal evidence to immunotherapy strategies
    Elisa Mattavelli, Valentina Da Prat, Salvatore Corallo, Alice Tartara, Simone Figini, Francesca De Simeis, Sofia Marino, Anna Uggè, Riccardo Caccialanza, Paolo Pedrazzoli, Angioletta Lasagna
    Immunotherapy.2026; 18(3): 223.     CrossRef
  • The modern perspective on the role of microbiota in childhood chemotherapy
    Almaz Kh. Islamgulov, Azat A. Murtazin, Viktor A. Malievsky, Linara R. Kalmeteva, Dilyara D. Prolygina, Gulshat A. Davletbaeva, Gulnara R. Gazizullina
    Russian Journal of Oncology.2026;[Epub]     CrossRef
  • Aging promotes the mitochondrial contact site and cristae organizing system complex dysfunction in metabolic-associated steatotic liver disease: A narrative review
    Bislom C. Mweene, Sepiso K. Masenga, Prasanna Katti, Prasanna Venkhatesh, Kit Neikirk, Andrea Marshall, Berwin Singh Swami Vetha, Ron McMillian, Annet Kirabo, Joyonna Gamble-George, Benjamin Rodriguez, Mohd Mabood Khan, Antentor Hinton
    Aging Advances.2026;[Epub]     CrossRef
  • Gut Microbiota and the Gut–Liver Axis in Liver Disease: From Chronic Viral Hepatitis to Cirrhosis, Hepatocellular Carcinoma, and Microbiome-Based Therapies
    Sniedze Laivacuma, Olga Oblate, Aleksejs Derovs
    Microorganisms.2025; 13(5): 1053.     CrossRef
  • Deciphering the circadian rhythm in colorectal cancer: a bibliometric analysis of research landscape and trends
    Linzi Chen, Zhongjie Wang, Ningkun Xiao, Jinhui Liu, Yuhan Tao, Sifang Zhang
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • Mechanism of activation of the Nrf2-Keap1 pathway by fermented Chinese herbal medicines via the gut-liver axis to alleviate cadmium-induced hepatotoxicity
    Li Jiang, Qiuhong Wu, Yilei Liang, Zhiwen Yang, Guang Fan, Pan Zhou, Xinyue Liu, Yachao Wang
    Environmental Chemistry and Ecotoxicology.2025; 7: 1300.     CrossRef
  • Associations between the effectiveness of sleeve gastrectomy and the composition and function of gut microbiome in obese rats
    Yifan Cao, Songhan Qin, Dandan Liu, Tao Zhang, Yin Wu, Ming Xie, Jiwei Wang
    Journal of Gastrointestinal Surgery.2025; 29(9): 102153.     CrossRef
  • Exploring the Epidemiologic Burden, Pathogenetic Features, and Clinical Outcomes of Primary Liver Cancer in Patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Scoping Review
    Mario Romeo, Fiammetta Di Nardo, Carmine Napolitano, Claudio Basile, Carlo Palma, Paolo Vaia, Marcello Dallio, Alessandro Federico
    Diabetology.2025; 6(8): 79.     CrossRef
  • The microbiome–cancer axis as a hidden contributor to early-onset tumorigenesis
    Azfar Jamal, Mohammad Azhar Kamal, Yaser E. Alqurashi, Esam S. Al-Malki, Mohammed M. Naiyer, Syed Arif Hussain, Haroonrashid M. Hattiwale
    Medical Oncology.2025;[Epub]     CrossRef
  • Tumor microenvironment and macroenvironment: A new perspective on holistic oncology
    Qun Chen, Kuirong Jiang, Michael S. Bronze, Min Li, Courtney W. Houchen, Yuqing Zhang
    Cancer Letters.2025; 634: 218076.     CrossRef
  • Gut–liver axis dysregulation and microbial dysbiosis in invasive liver abscess: a narrative review
    Xiaoshuai Bai, Zhen Wang, Kai Guo, Ping Zhou, Lei Shi
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • The role of hypothyroidism in cirrhosis pathogenesis: A retrospective cohort study and multi-omics integration analysis
    Ziyang Yang, Weixuan Liang, Qi Zhang, Can Weng, Hao Deng, Zhuofeng Wen, Jingyi Wu, Jingwen Deng, Zhixin Xie, Yiwei Lin, Xiuling Fu, Chengxin Gu, Tao Yang, Hui Yang, Jiyuan Zhou, Renato Polimanti
    PLOS Genetics.2025; 21(11): e1011947.     CrossRef
  • Recent Advancements in Known and Emerging Risk Factors of Hepatocellular Carcinoma
    Muhammad Masroor Hussain, Bi Feng, Ju‐Mei Wang, Ao‐Qiang Zhai, Fu‐yu Li, Hai‐jie Hu
    Cancer Medicine.2025;[Epub]     CrossRef
  • Harnessing the microbiota-gut–brain axis to prevent and treat pediatric neurodevelopmental disorders: translational insights and strategies
    Shamma H. Alkuwaiti, Jurga Skrabulyte-Barbulescu, Lidya K. Yassin, Saif Almazrouei, Dana Aldhaheri, Mahra Alderei, Shamsa BaniYas, Shamsa H. Alshamsi, Abeer Alnuaimi, Sara Saeed, Mohammad Alawadhi, Paulina Rutkowska-Gauvry, Fatima Y. Ismail, Mohammad I. K
    Journal of Translational Medicine.2025;[Epub]     CrossRef
  • Gut microbiota–derived metabolites in immunomodulation and gastrointestinal cancer immunotherapy
    Wenbin Luo, Ruoyun Li, Chaofan Pan, Changjiang Luo
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Analyzing the gut liver axis: a dual role of the microbiome in the genesis, progression, and treatment of liver cell carcinoma
    Qianzhu Li, Yafang Liu
    Frontiers in Microbiology.2025;[Epub]     CrossRef
  • Cross-platform assessment of short-form video quality on the gut–liver axis: informational integrity and engagement disparity
    Man Sun, Dan Zang, Jun Chen
    Frontiers in Cellular and Infection Microbiology.2025;[Epub]     CrossRef
  • The Dual Role of Gut Microbiota and Their Metabolites in Hepatocellular Carcinoma: A Context-Dependent Framework
    Shuyu Zuo, Junhui Ma, Xue Li, Zhengyang Fan, Xiao Li, Yingen Luo, Lei Su
    Microorganisms.2025; 14(1): 73.     CrossRef
  • 14,192 View
  • 464 Download
  • 30 Web of Science
  • Crossref

Correspondence

Hepatic neoplasm

  • 5,444 View
  • 53 Download

Reply to Correspondence

Hepatic neoplasm

  • 5,196 View
  • 51 Download

Letter to the Editor

Hepatic neoplasm

Citations

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  • Correspondence to letter to the editor on “Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis”
    Moon Haeng Hur, Yoon Jun Kim
    Clinical and Molecular Hepatology.2025; 31(1): e93.     CrossRef
  • 7,011 View
  • 65 Download
  • Crossref

Editorials

Hepatic neoplasm

Citations

Citations to this article as recorded by  Crossref logo
  • Distinct tumor immune microenvironment modulation by anti-PD-1/PD-L1, VEGF, and CTLA-4 blockade provides a rationale for triplet therapy in hepatocellular carcinoma
    Hideki Iwamoto, Hironori Koga, Takumi Kawaguchi
    Clinical and Molecular Hepatology.2026; 32(1): e38.     CrossRef
  • Correspondence to editorial 2 on “Genomic biomarkers to predict response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma: insights from the IMbrave150 trial”
    Sun Young Yim, Sung Hwan Lee, Ji Hoon Kim, Sunyoung S Lee, Ahmed O Kaseb, Ju-Seog Lee
    Clinical and Molecular Hepatology.2025; 31(1): e84.     CrossRef
  • T lymphocyte-based immune response and therapy in hepatocellular carcinoma: focus on TILs and CAR-T cells
    Thikra Majid Muhammed, Saade Abdalkareem Jasim, Ahmed Hussein Zwamel, Safia Obaidur Rab, Suhas Ballal, Abhayveer Singh, Anima Nanda, Subhashree Ray, Ahmed Hjazi, Hatif Abdulrazaq Yasin
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(8): 10007.     CrossRef
  • Genetic insights into sarcomatoid hepatocellular carcinoma: Critical role of ARID2 in pathogenesis and immune feature: Editorial on “Integrated molecular characterization of sarcomatoid hepatocellular carcinoma”
    Naoshi Nishida
    Clinical and Molecular Hepatology.2025; 31(2): 635.     CrossRef
  • Addressing the Complexities of Pre-Liver Transplant Immune Checkpoint Inhibitors for Hepatocellular Carcinoma: A Response to Recent Commentaries
    Mohammad Saeid Rezaee-Zavareh, Zhiyong Guo, Ju Dong Yang
    Journal of Hepatology.2024;[Epub]     CrossRef
  • 8,602 View
  • 95 Download
  • 4 Web of Science
  • Crossref

Hepatic neoplasm

Citations

Citations to this article as recorded by  Crossref logo
  • Locoregional Therapies for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus
    Ramanpreet Singh, Mina S. Makary
    Journal of Gastrointestinal Cancer.2025;[Epub]     CrossRef
  • Atezolizumab Plus Bevacizumab for Advanced Hepatocellular Carcinoma with Macroscopic Vascular Invasion: An Inverse Probability of Treatment Weighted Analysis
    Jihoon Kim, Jin-Hyoung Kim, Byung Soo Im, Gun Ha Kim, Hee Ho Chu, Dong Il Gwon, Ji Hoon Shin, Ju Hyun Shim, Sang Min Yoon, Sehee Kim
    Cancers.2025; 18(1): 33.     CrossRef
  • 5,422 View
  • 96 Download
  • 2 Web of Science
  • Crossref

Hepatic neoplasm

  • 6,414 View
  • 80 Download

Original Article

Hepatic neoplasm

Transarterial radioembolization versus tyrosine kinase inhibitor in hepatocellular carcinoma with portal vein thrombosis
Moon Haeng Hur, Yuri Cho, Do Young Kim, Jae Seung Lee, Gyoung Min Kim, Hyo-Cheol Kim, Dong Hyun Sinn, Dongho Hyun, Han Ah Lee, Yeon Seok Seo, In Joon Lee, Joong-Won Park, Yoon Jun Kim
Clin Mol Hepatol 2023;29(3):763-778.
Published online May 30, 2023
DOI: https://doi.org/10.3350/cmh.2023.0076
Background/Aims
Transarterial radioembolization (TARE) has shown promising results in treating advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). However, whether TARE can provide superior or comparable outcomes to tyrosine kinase inhibitor (TKI) in patients with HCC and PVTT remains unclear. We compared the outcomes of TARE and TKI therapy in treatment-naïve patients with locally advanced HCC and segmental or lobar PVTT.
Methods
This multicenter study included 216 patients initially treated with TARE (n=124) or TKI (sorafenib or lenvatinib; n=92) between 2011 and 2021. Baseline characteristics were balanced using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS) and objective response rate (ORR).
Results
In the unmatched cohort, the median OS of the TARE and TKI groups were 28.2 and 7.2 months, respectively (p<0.001), and the TARE group experienced significantly and independently longer OS compared to the TKI group (adjusted hazard ratio=0.41, 95% confidence interval=0.28–0.60, p<0.001). Similar results were observed in the study cohorts balanced with IPTW (p=0.003) or PSM (p=0.004). Although PFS was comparable between the two groups, the TARE group showed a trend of prolonged PFS in a subpopulation of patients with Vp1 or Vp2 PVTT (p=0.052). In the matched cohorts, the ORR of the TARE group was 53.0–56.7%, whereas that of the TKI group was 12.3–15.0%.
Conclusions
For patients with advanced HCC with segmental or lobar PVTT and well-preserved liver function, TARE may provide superior OS compared to sorafenib or lenvatinib.

Citations

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  • Transarterial radioembolization versus atezolizumab-bevacizumab for the treatment of hepatocellular carcinoma with portal vein tumor thrombosis
    Youngsu Park, Yuri Cho, Seung Up Kim, Aryoung Kim, Hyunjae Shin, Hyo-Cheol Kim, In Joon Lee, Gyoung Min Kim, Dongho Hyun, Yunmi Ko, Jeayeon Park, Jae Woong Yoon, Gyung Sun Lim, Moon Haeng Hur, Yun Bin Lee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan
    Diagnostic and Interventional Imaging.2026; 107(1): 25.     CrossRef
  • Transarterial radioembolization challenges immunotherapy as first-line care for hepatocellular carcinoma with portal vein tumor thrombosis
    Anna Pellat, Maxime Barat
    Diagnostic and Interventional Imaging.2026; 107(1): 1.     CrossRef
  • Screening the advantageous population for liver cancer undergoing yttrium-90 microsphere selective internal radiation therapy
    Licong Liang, Yuchan Liang, Wensou Huang, Yongjian Guo, Jingjun Huang, Jingwen Zhou, Liteng Lin, Xinxin Nie, Mingyue Cai, Kangshun Zhu
    Liver Research.2026; 10(1): 61.     CrossRef
  • Progress in hepatoprotective strategies during TACE treatment
    Chenlu Qian, Yan Wu, Chuan Yin, Jie Gao
    Advanced Interventional Materials.2026; 1(1): 100012.     CrossRef
  • Locoregional Therapies for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus
    Ramanpreet Singh, Mina S. Makary
    Journal of Gastrointestinal Cancer.2025;[Epub]     CrossRef
  • Pre-transplant downstaging strategies for hepatocellular carcinoma with portal vein tumor thrombus: Current therapies and future challenges
    Zong-Yang Li, Cheng Xie, Hong-Qiao Cai
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Radioembolization in Hepatocellular Carcinoma: Indications and Outcomes
    Bahareh Gholami, Ali Afrasiabi, Paolo Varela, Samira Gholami, Andrew Moon, Alexander Villalobos, David Mauro, Bryan Harris, Hyeon Yu, Nima Kokabi
    Journal of Gastrointestinal Cancer.2025;[Epub]     CrossRef
  • Radio-magnetic dual-functional microspheres for magnetic hyperthermia therapy combined with radioembolization of hepatocellular carcinoma
    Manran Wu, Dong Wang, Yu Qin, Xunhao Qi, Qian Huang, Xingwei Sun, Yong Jin, Ran Zhu, Guanglin Wang, Pengfei Rong
    Materials Today Bio.2025; 35: 102553.     CrossRef
  • Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study
    Bo Hyun Kim, Hee Chul Park, Tae Hyun Kim, Young-Hwan Koh, Jung Yong Hong, Yuri Cho, Dong Hyun Sinn, Boram Park, Joong-Won Park
    JHEP Reports.2024; 6(4): 100991.     CrossRef
  • Comparison between Nivolumab and Regorafenib as Second-line Systemic Therapies after Sorafenib Failure in Patients with Hepatocellular Carcinoma
    Hong Jun Lee, Jae Seung Lee, Hyesung So, Ja Kyung Yoon, Jin-Young Choi, Hye Won Lee, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Do Young Kim
    Yonsei Medical Journal.2024; 65(7): 371.     CrossRef
  • Recent Hepatocellular Carcinoma Managements in Korea: Focus on the Updated Guidelines in 2022
    Yuri Cho, Bo Hyun Kim, Young-Suk Lim
    Digestive Disease Interventions.2024; 08(03): 169.     CrossRef
  • Research Progress in Predicting Hepatocellular Carcinoma with Portal Vein Tumour Thrombus in the Era of Artificial Intelligence
    Yaduo Li, Ningning Fan, Xu He, Jianjun Zhu, Jie Zhang, Ligong Lu
    Journal of Hepatocellular Carcinoma.2024; Volume 11: 1429.     CrossRef
  • Liver transplantation following two conversions in a patient with huge hepatocellular carcinoma and portal vein invasion: A case report
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Letter to the Editor

Clinical significance of the discrepancy between radiological findings and biochemical responses in atezolizumab plus bevacizumab for hepatocellular carcinoma
Hideki Iwamoto, Shigeo Shimose, Takashi Niizeki, Hironori Koga, Takuji Torimura, The Kurume Liver Cancer Study Group of Japan
Clin Mol Hepatol 2022;28(3):575-579.
Published online April 21, 2022
DOI: https://doi.org/10.3350/cmh.2022.0047

Citations

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Original Article

Liver fibrosis, cirrhosis, and portal hypertension

Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats
Ki Tae Yoon, Hongqun Liu, Jing Zhang, Sojung Han, Samuel S. Lee
Clin Mol Hepatol 2022;28(2):232-241.
Published online January 5, 2022
DOI: https://doi.org/10.3350/cmh.2021.0141
Background/Aims
Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy.
Methods
Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy.
Results
Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls.
Conclusion
Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.

Citations

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Review

Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma
Pil Soo Sung
Clin Mol Hepatol 2022;28(3):333-350.
Published online October 19, 2021
DOI: https://doi.org/10.3350/cmh.2021.0308
The tumor microenvironment generally shows a substantial immunosuppressive activity in hepatocellular carcinoma (HCC), accounting for the suboptimal efficacy of immune-based treatments for this difficult-to-treat cancer. The crosstalk between tumor cells and various cell types in the tumor microenvironment is strongly related to HCC progression and treatment resistance. Monocytes are recruited to the HCC tumor microenvironment by various factors and become tumor-associated macrophages (TAMs) with distinct phenotypes. TAMs often contribute to weakened tumor-specific immune responses and a more aggressive phenotype of malignancy. Recent single-cell RNA-sequencing data have demonstrated the central roles of specific TAMs in tumorigenesis and treatment resistance by their interactions with various cell populations in the HCC tumor microenvironment. This review focuses on the roles of TAMs and the crosstalk between TAMs and neighboring cell types in the HCC tumor microenvironment.

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Editorial

Liver fibrosis, cirrhosis, and portal hypertension

Leaky gut-derived tumor necrosis factor-α causes sarcopenia in patients with liver cirrhosis
Takumi Kawaguchi, Takuji Torimura
Clin Mol Hepatol 2022;28(2):177-180.
Published online August 26, 2021
DOI: https://doi.org/10.3350/cmh.2021.0246

Citations

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Original Article

Liver fibrosis, cirrhosis, and portal hypertension

Association between serum tumor necrosis factor-α and sarcopenia in liver cirrhosis
Ji Won Han, Da In Kim, Hee Chul Nam, U Im Chang, Jin Mo Yang, Do Seon Song
Clin Mol Hepatol 2022;28(2):219-231.
Published online July 20, 2021
DOI: https://doi.org/10.3350/cmh.2021.0082
Background/Aims
Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear.
Methods
Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease.
Results
LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues.
Conclusions
These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

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Review

Hepatic neoplasm

Radiomics and radiogenomics of primary liver cancers
Woo Kyoung Jeong, Neema Jamshidi, Ely Richard Felker, Steven Satish Raman, David Shinkuo Lu
Clin Mol Hepatol 2019;25(1):21-29.
Published online November 16, 2018
DOI: https://doi.org/10.3350/cmh.2018.1007
Concurrent advancements in imaging and genomic biomarkers have created opportunities to identify non-invasive imaging surrogates of molecular phenotypes. In order to develop such imaging surrogates radiomics and radiogenomics/imaging genomics will be necessary; there has been consistent progress in these fields for primary liver cancers. In this article we evaluate the current status of the field specifically with regards to hepatocellular carcinoma and intrahepatic cholangiocarcinoma, highlighting some of the up and coming results that were presented at the annual Radiological Society of North America Conference in 2017. There are an increasing number of studies in this area with a bias towards quantitative feature measurement, which is expected to benefit reproducibility of the findings and portends well for the future development of biomarkers for diagnosis, prognosis, and treatment response assessment. We review some of the advancements and look forward to some of the exciting future applications that are anticipated as the field develops.

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Case Report

Hepatic neoplasm

Complete response of advanced hepatocellular carcinoma to sorafenib : another case and a comprehensive review
Tae Suk Kim, Ji Hoon Kim, Baek hui Kim, Young-Sun Lee, Yang Jae Yoo, Seong Hee Kang, Sang-June Suh, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kwan Soo Byun
Clin Mol Hepatol 2017;23(4):340-346.
Published online June 20, 2017
DOI: https://doi.org/10.3350/cmh.2016.0070
Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCVrelated HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.

Citations

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Liver Imagings

Hepatic neoplasm

Aggressive tumor recurrence after radiofrequency ablation for hepatocellular carcinoma
Tae Wook Kang, Hyo Keun Lim, Dong Ik Cha
Clin Mol Hepatol 2017;23(1):95-101.
Published online March 24, 2017
DOI: https://doi.org/10.3350/cmh.2017.0006
Image-guided radiofrequency ablation (RFA) is an evolving and growing treatment option for patients with hepatocellular carcinoma (HCC) and hepatic metastasis. RFA offers significant advantages as it is less invasive than surgery and carries a low risk of major complications. However, serious complications, including aggressive tumor recurrence, may be observed during follow-up, and recently, mechanical or thermal damage during RFA has been proposed to be one of the causes of this kind of recurrence. Although the exact mechanism of this still remains unclear, physicians should be familiar with the imaging features of aggressive tumor recurrence after RFA for HCC and its risk factors. In addition, in order to prevent or minimize this newly recognized tumor recurrence, a modified RFA technique, combined RFA treatments with transarterial chemoembolization, and cryoablation can be used as alternative treatments. Ultimately, combining an understanding of this potential complication of RFA with an understanding of the possible risk factors for aggressive tumor recurrence and choosing alternative treatments are crucial to optimize clinical outcomes in each patient with HCC.

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Hepatic neoplasm

Intraductal malignant tumors in the liver mimicking cholangiocarcinoma: Imaging features for differential diagnosis
Ah Yeong Kim, Woo Kyoung Jeong
Clin Mol Hepatol 2016;22(1):192-197.
Published online March 28, 2016
DOI: https://doi.org/10.3350/cmh.2016.22.1.192

Citations

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Original Articles

Hepatic neoplasm

Survival outcomes of hepatic resection compared with transarterial chemoembolization or sorafenib for hepatocellular carcinoma with portal vein tumor thrombosis
Jung Min Lee, Byoung Kuk Jang, Yoo Jin Lee, Wang Yong Choi, Sei Myong Choi, Woo Jin Chung, Jae Seok Hwang, Koo Jeong Kang, Young Hwan Kim, Anil Kumar Chauhan, Soo Young Park, Won Young Tak, Young Oh Kweon, Byung Seok Kim, Chang Hyeong Lee
Clin Mol Hepatol 2016;22(1):160-167.
Published online March 28, 2016
DOI: https://doi.org/10.3350/cmh.2016.22.1.160
Background/Aims
Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT.
Methods
Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II).
Results
The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both P<0.001), and did not differ significantly between the latter two groups (P=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (P=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, P=0.036; HR vs. sorafenib: hazard ratio=2.262, P=0.006), involved lobe (hazard ratio=1.705, P=0.008), PVTT type (hazard ratio=1.617, P=0.013), and CTP class (hazard ratio=1.712, P=0.012).
Conclusions
Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.

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Hepatic neoplasm

Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease
Chansik An, Youn Ah Choi, Dongil Choi, Yong Han Paik, Sang Hoon Ahn, Myeong-Jin Kim, Seung Woon Paik, Kwang-Hyub Han, Mi-Suk Park
Clin Mol Hepatol 2015;21(3):279-286.
Published online September 30, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.3.279
Background/Aims

The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate.

Methods

Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients.

Results

The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234).

Conclusions

The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC.

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    Xuqi Sun, Dandan Hu, Yaojun Zhang, Ning Lyu, Li Xu, Qifeng Chen, Jinfa Lai, Minshan Chen, Ming Zhao
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  • Discrepancy between the Actual Clinical Status of Patients with Hepatocellular Carcinoma and Expectations from Hepatocellular Carcinoma Surveillance: a Single-Center Study
    Nak Min Kim, Young Seok Doh, Ji Woong Jang, Seok-Hwan Kim, Hyuk Soo Eun, Jae Hyuck Jun, Sae Hee Kim, Il Hyun Baek, Sung Hee Jung
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    Keungmo Yang, Pil S. Sung, Young K. You, Dong G. Kim, Jung S. Oh, Ho J. Chun, Jeong W. Jang, Si H. Bae, Jong Y. Choi, Seung K. Yoon
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    Korosh Khalili
    Gastroenterology.2019; 157(3): 899.     CrossRef
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    Isabelle Durot, Stephanie R. Wilson, Jürgen K. Willmann
    Abdominal Radiology.2018; 43(4): 819.     CrossRef
  • Extracellular contrast agent-enhanced MRI: 15-min delayed phase may improve the diagnostic performance for hepatocellular carcinoma in patients with chronic liver disease
    Si Eun Lee, Chansik An, Shin Hye Hwang, Jin-Young Choi, Kyunghwa Han, Myeong-Jin Kim
    European Radiology.2018; 28(4): 1551.     CrossRef
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    Sally Ann Tran, An Le, Changqing Zhao, Joseph Hoang, Lee Ann Yasukawa, Susan Weber, Linda Henry, Mindie H Nguyen
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  • Spontaneous Slowing and Regressing of Tumor Growth in Childhood/Adolescent Papillary Thyroid Carcinomas Suggested by the Postoperative Thyroglobulin-Doubling Time
    Toshihiko Kasahara, Akira Miyauchi, Takumi Kudo, Eijun Nishihara, Mitsuru Ito, Yasuhiro Ito, Minoru Kihara, Akihiro Miya
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    Lydia S. Y. Tang, Emily Covert, Eleanor Wilson, Shyam Kottilil
    JAMA.2018; 319(17): 1802.     CrossRef
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    Neil J. Mehta, Aygul Dogan Celik, Marion G. Peters
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    Lars Bossen, Henning Grønbæk, Peter Lykke Eriksen, Peter Jepsen
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  • Adding to the evidence base: Effectiveness of hepatocellular carcinoma surveillance in clinical practice
    Prashant Pandya, Fasiha Kanwal
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  • Tumor Volume Doubling Time as a Dynamic Prognostic Marker for Patients with Hepatocellular Carcinoma
    Jong Kwan Kim, Hyung-Don Kim, Mi-Jung Jun, Sung-Cheol Yun, Ju Hyun Shim, Han Chu Lee, Danbi Lee, Jihyun An, Young-Suk Lim, Young-Hwa Chung, Yung Sang Lee, Kang Mo Kim
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  • Multiplication of Tumor Volume by Two Tumor Markers Is a Post-Resection Prognostic Predictor for Solitary Hepatocellular Carcinoma
    Shin Hwang, Gi-Won Song, Young-Joo Lee, Ki-Hun Kim, Chul-Soo Ahn, Deok-Bog Moon, Tae-Yong Ha, Dong-Hwan Jung, Gil-Chun Park, Sung-Gyu Lee
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  • Crossref

Hepatic neoplasm

Predictive factors of contrast-enhanced ultrasonography for the response to transarterial chemoembolization in hepatocellular carcinoma
Kil Hyo Park, Soon Ha Kwon, Yong Sub Lee, Soung Won Jeong, Jae Young Jang, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim, Yong Jae Kim
Clin Mol Hepatol 2015;21(2):158-164.
Published online June 26, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.2.158
Background/Aims

The predictive role of contrast-enhanced ultrasonography (CEUS) before performing transarterial chemoembolization (TACE) has not been determined. We assessed the possible predictive factors of CEUS for the response to TACE.

Methods

Seventeen patients with 18 hepatocellular carcinoma (HCC) underwent TACE. All of the tumors were studied with CEUS before TACE using a second-generation ultrasound contrast agent (SonoVue®, Bracco, Milan, Italy). The tumor response to TACE was classified with a score between 1 and 4 according to the remaining enhancing-tumor percentage based on modified response evaluation criteria in solid tumors (mRECIST): 1, enhancing tumor <25%; 2, 25%≤enhancing tumor<50%; 3, 50%≤enhancing tumor<75%; and 4, enhancing tumor≥75%). A score of 1 was defined as a "good response" to TACE. The predictive factors for the response to TACE were evaluated during CEUS based on the maximum tumor diameter, initial arterial enhancing time, arterial enhancing duration, intensity of arterial enhancement, presence of a hypoenhanced pattern, and the feeding artery to the tumor.

Results

The median tumor size was 3.1 cm. The distribution of tumor response scores after TACE in all tumors was as follows: 1, n=11; 2, n=4; 3, n=2; and 4, n=1. Fifteen tumors showed feeding arteries. The presence of a feeding artery and the tumor size (≤5 cm) were the predictive factors for a good response (P=0.043 and P=0.047, respectively).

Conclusions

The presence of a feeding artery and a tumor size of less than 5 cm were the predictive factors for a good response of HCC to TACE on CEUS.

Citations

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Case Report

Hepatic neoplasm

Low-dose steroid-induced tumor lysis syndrome in a hepatocellular carcinoma patient
Jin Ok Kim, Dae Won Jun, Hye Jin Tae, Kang Nyeong Lee, Hang Lak Lee, Oh Young Lee, Ho Soon Choi, Byung Chul Yoon, Joon Soo Hahm
Clin Mol Hepatol 2015;21(1):85-88.
Published online March 25, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.1.85

Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.

Citations

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Liver Imagings

Hepatic neoplasm

Composite liver tumors: A radiologic-pathologic correlation
Megha Nayyar, David K. Imagawa, Temel Tirkes, Aram N. Demirjian, Roozbeh Houshyar, Kumar Sandrasegaran, Chaitali S. Nangia, Tara Seery, P Bhargava, Joon II Choi, Chandana Lall
Clin Mol Hepatol 2014;20(4):406-410.
Published online December 24, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.4.406

Bi-phenotypic neoplasm refers to tumors derived from a common cancer stem cell with unique capability to differentiate histologically into two distinct tumor types. Bi-phenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC), although a rare tumor, is important for clinicians to recognize, since treatment options targeting both elements of the tumor are crucial. Imaging findings of bi-phenotypic HCC-CC are not specific and include features of both HCC and CC. A combination of imaging and immuno-histochemical analysis is usually needed to make the diagnosis.

Citations

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  • Overexpression of lncRNA MT1JP Mediates Apoptosis and Migration of Hepatocellular Carcinoma Cells by Regulating miR-24-3p


    Qiu-Li Shan, Ning-Ning Chen, Gui-Zhi Meng, Fan Qu
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Benign liver tumors and cystic disease of liver

Hepatic inflammatory pseudotumor misinterpreted as hepatocellular carcinoma
Jae Yoon Jeong, Joo Hyun Sohn, Tae Yeob Kim, Woo Kyoung Jeong, Jinoo Kim, Ju Yeon Pyo, Young Ha Oh
Korean J Hepatol 2012;18(2):239-244.
Published online June 26, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.2.239

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    Peng Xie, Zhong-Jian Liao, Lu Xie, Junyuan Zhong, Xiaodong Zhang, Wei Yuan, Yujin Yin, Tianxian Chen, Huizhen Lv, Xinglin Wen, Xiaochun Wang, Ling Zhang
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    Michelle Oliveira Iwata, Andrea Helena Érnica Bisol, Maria Osana da Silva Antônio Filho, Gabriel Gouveia Coelho de Moraes, Alexandre da Silva Leopoldino
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    晓菡 张
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    Linda Calistri, Davide Maraghelli, Cosimo Nardi, Sofia Vidali, Vieri Rastrelli, Laura Crocetti, Luigi Grazioli, Stefano Colagrande
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    Size Wu, Dongsheng Zuo, Yamin Hong
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    J. B. M. Christ, A. Tannapfel, G. Kukuk, K. Schlottmann, C. Straßburg, A. Schneidewind
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    Meng Fei Xian, Wen Tong Lan, Hui Huang, Dan Zeng, Zuo Feng Xu
    Ultrasound Quarterly.2017; 33(3): 242.     CrossRef
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    Wei Yang, Kun Yan, Song Wang, Ying Dai, Wei Wu, Shan-Shan Yin, Min-Hua Chen
    Ultrasound in Medicine & Biology.2016; 42(1): 82.     CrossRef
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    Jon Etxano Cantera, María Páramo Alfaro, David Cano Rafart, Romina Zalazar, Maite Millor Muruzabal, Paula García Barquín, Isabel Vivas Pérez
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    Radu Badea, Antonia Alexandra Veres, Vasile Andreica, Cosmin Caraiani, Nadim Al-Hajjar, Roxana Sechel, Liliana Chiorean
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    Hyun Woong Lee
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Case Report

Benign liver tumors and cystic disease of liver

Concurrent hepatic adenomatoid tumor and hepatic hemangioma: a case report
Ji-Beom Kim, Eunsil Yu, Ju-Hyun Shim, Gi-Won Song, Gwang Un Kim, Young-Joo Jin, Ho-Seop Park
Korean J Hepatol 2012;18(2):229-234.
Published online June 26, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.2.229

A 45-year-old male with alleged asymptomatic hepatic hemangioma of 4 years duration had right upper-quadrant pain and was referred to a tertiary hospital. Computed tomography and magnetic resonance imaging scans revealed a hypervascular mass of about 7 cm containing intratumoral multilobulated cysts. A preoperative liver biopsy was performed, but this failed to provide a definitive diagnosis. The patient underwent a partial hepatectomy of segments IV and VIII. The histologic findings revealed multifocal proliferation of flattened or cuboidal epithelioid cells and a highly vascular edematous stroma. Immunohistochemistry findings demonstrated that the epithelioid tumor cells were positive for cytokeratin (AE1/AE3), vimentin, calretinin, and cytokeratin 5/6, and were focally positive for CD10, and negative for WT1 and CD34, all of which support their mesothelial origin. Immunohistochemistry for a mesothelial marker should be performed for determining the presence of an adenomatoid tumor when benign epithelioid cells are seen.

Citations

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    Ruoji Zhou, Hanlin L Wang
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    Lei Bi
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    Georgia Karpathiou, Kenzo Hiroshima, Michel Peoc’h
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Original Articles

Analysis of prognostic factors and 5-year survival rate in patients with hepatocellular carcinoma: a single-center experience
Sang Seok Lee, Hyun Sung Shin, Hyung Joon Kim, Su Jin Lee, Hyun Suk Lee, Kyung Hee Hyun, Yong Hyun Kim, Byoung Woon Kwon, Jin Hyung Han, Hoon Choi, Bae Hwan Kim, Joon Hyuk Lee, Ha Yan Kang, Hyun Deok Shin, Il Han Song
Korean J Hepatol 2012;18(1):48-55.
Published online March 22, 2012
DOI: https://doi.org/10.3350/kjhep.2012.18.1.48
Background/Aims

Hepatocellular carcinoma (HCC), which is the third most common cancer in Korea, has a very poor prognosis. However, only a few studies have performed a comprehensive survival-related analysis in all patients who were consecutively diagnosed and treated over a given period of time. The aim of this study was to determine the 5-year survival rate and its prognostic factors among HCC patients.

Methods

In total, 257 patients who were consecutively diagnosed with HCC between January 2000 and December 2003 were followed until death or until December 2008. We analyzed their survival outcomes according to their clinical characteristics, tumor staging, and treatment modalities, and determined the independent prognostic factors affecting survival.

Results

The patients were aged 59±10 years (mean±SD). During the follow-up period, 223 patients (86.8%) died and the overall median survival was 10.8 months; the 1-, 3-, and 5-year survival rates were 44.4%, 21.0%, and 12.1%, respectively. The outcomes in patients with tumor node metastasis (TNM) stage I or II and Child-Pugh class A or B were significantly better with surgical resection than with other treatment modalities (P<0.01). Patients who underwent supplementary transcatheter arterial chemoembolization as a second-line treatment after surgical resection had better outcomes than those who underwent surgical resection alone (P=0.02). Initial symptoms, Child-Pugh class, serum alpha-fetoprotein, tumor size, portal vein thrombosis, and TNM stage were found to be independent prognostic factors for survival among HCC patients.

Conclusions

This retrospective cohort study elucidated survival outcomes and prognostic factors affecting survival in HCC patients at a single center.

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Combination treatment with intrahepatic arterial infusion and intratumoral injection chemotherapy in patients with far-advanced hepatocellular carcinoma and arterioportal or arteriovenous shunts: preliminary results
Ja Seon Kim, Young Min Park, Nha Young Kim, Han Kyeol Yun, Ki Jong Lee, Bo Hyun Kim, Sang Jong Park, Jae Woo Yeon, Guhung Jung
Korean J Hepatol 2011;17(2):120-129.
Published online June 23, 2011
DOI: https://doi.org/10.3350/kjhep.2011.17.2.120
Background/Aims

Combination treatment consisting of hepatic arterial infusion chemotherapy with epirubicin and cisplatin (HAIC-EC) and systemic infusion of low-dose 5-fluorouracil (5-FU) are sometimes effective against advanced hepatocellular carcinoma (HCC). However, there is no effective treatment for advanced HCCs with arterioportal shunts (APS) or arteriovenous shunts (AVS).

Methods

We investigated a response and adverse events of a new combination protocol of repeated HAIC-EC and percutaneous intratumoral injection chemotherapy with a mixture of recombinant interferon-gamma (IFN-γ) and 5-FU (PIC-IF) in patients with far-advanced HCCs with large APSs or AVSs.

Results

There was a complete response (CR) for the large vascular shunts in all three patients and for all tumor burdens in two patients. Significant side effects were flu-like symptoms (grade 2) and bone marrow suppression (grade 2 or 3) after each cycle, but these were well-tolerated.

Conclusions

These results suggest that the combination of HAIC-EC and PIC-IF is a new and promising approach for advanced HCC accompanied by a large APS or AVS.

Citations

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Liver Imaging

Neuroendocrine tumors of the Liver
Won Jae Lee
Korean J Hepatol 2009;15(4):528-532.
Published online December 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.4.528
.

Citations

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Liver Pathology

Well differentiated hepatocellular carcinoma: Pathological diagnosis of needle biopsied Liver tissue
Jae Yeon Seok , Young Nyun Park
Korean J Hepatol 2009;15(1):96-100.
Published online March 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.1.96
  • 4,974 View
  • 29 Download

Case Reports

A case of advanced hepatocellular carcinoma with portal vein tumor invasion controlled by percutaneous ethanol injection therapy
Ik Yoon, M.D., Hyung Joon Yim, M.D., Jin Nam Kim, M.D., Sun Min Park, M.D., Jeong Han Kim, M.D., Seung Hwa Lee, M.D.1, Hwan Hoon Chung, M.D.1, Hong Sik Lee, M.D., Sang Woo Lee, M.D., Jai Hyun Choi, M.D.
Korean J Hepatol 2009;15(1):90-95.
Published online March 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.1.90
Portal vein invasion is a grave prognostic indicator in the setting of hepatocellular carcinoma (HCC). There is currently no effective method for preventing the invasion of HCC into the main portal vein. We report here a case of advanced HCC with portal vein tumor thrombosis that was effectively treated with percutaneous ethanol injection (PEI), having previously enabled subsequent successive transarterial chemoembolization (TACE). A 60-year-old male patient was diagnosed with a huge HCC, based on computed tomography and angiographic findings. Despite two sessions of TACE, the tumor invaded the right portal vein. PEI was performed on the malignant portal vein thrombosis, and three sessions thereof reduced the extent of tumor thrombi in the portal vein. Successive TACEs were performed to treat the HCC in the hepatic parenchyma. The patient was still living 19 months after the first PEI with no evidence of tumor recurrence, and his liver function remained well preserved. (Korean J Hepatol 2008;15:90-95)

Citations

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    Abdominal Radiology.2022; 47(2): 858.     CrossRef
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A Case of Solitary Fibrous Tumor of the Liver
Soo-Yeong Kwak, M.D., Geum-Youn Gwak, M.D., Won-Kyoung Yun, M.D., Hyo-Jin Kim, M.D.1, In-Gu Do, M.D.2, Jae-Won Joh, M.D.3, Cheol Keun Park, M.D.2
Korean J Hepatol 2007;13(4):560-564.
Published online December 20, 2007
DOI: https://doi.org/10.3350/kjhep.2007.13.4.560
A 46-year-old woman was found to have a huge liver mass that was detected by abdominal ultrasonography. Abdominal CT and MRI showed a 10 cm-sized, encapsulated mass occupying the anterior segment of the right hepatic lobe. Extended right hemihepatectomy was performed and pathological examination revealed fibroblast-like spindle cells within dense deposits of collagen. On immunohistochemical staining, these spindle tumor cells showed an intense CD34 immunoreactivity. The patient is alive without evidence of tumor recurrence 7 months after the resection. Solitary fibrous tumor is a very rare neoplasm found in the liver parenchyma, and it has been reported in less than 30 patients in the English literature. We present here the first such case in Korea. (Korean J Hepatol 2007;13:560-564)

Citations

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    Ka-Jeong Kim, Hyung-Gon Moon, Sang-Ho Jeong, Chi-Young Jeong, Young-Tae Ju, Eun-Jung Jung, Young-Joon Lee, Sang-Kyung Choi, Woo-Song Ha, Soon-Tae Park, Soon-Chan Hong
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    Dimitris P Korkolis, Katerina Apostolaki, Chrysanthi Aggeli, George Plataniotis, Emmanuel Gontikakis, Dimitra Volanaki, Maria Sebastiadou, Dimitris Dimitroulopoulos, Dimitris Xinopoulos, George N Zografos, Perikles P Vassilopoulos
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Original Article

Efficacy of Transarterial Chemolipiodolization with or without 3-Dimensional Conformal Radiotherapy for Huge HCC with Portal Tumor Thrombosis
Chan Ran You, M.D., Jeong Won Jang, M.D., Seok Hui Kang, M.D., Si Hyun Bae, M.D., Jong Young Choi, M.D., Seung Kew Yoon, M.D., Ihl Bhong Choi, M.D.1, Dong Hoon Lee, M.D.2, Ho Jong Chun, M.D.2, Byung Gil Choi, M.D.2
Korean J Hepatol 2007;13(3):378-386.
Published online September 20, 2007
DOI: https://doi.org/10.3350/kjhep.2007.13.3.378
Background/Aims
The treatment efficacy for advanced hepatocellular carcinoma is poor. This study examined the efficacy and toxicity of 3-dimensional conformal radiotherapy (3D-CRT) in combination with transarterial chemolipiodolization (TACL) for a huge hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods: From March 2001 to November 2004, 49 patients with advanced HCC with PVTT (size>8 cm, modified UICC stage IVa) were enrolled in this retrospective study. Twenty two patients underwent more than 2 cycles of TACL (adriamycin 50 mg/m2, cisplatin 60 mg/m2, 5-fluorouracil 200 mg/m2 every 4-6 weeks) without 3D-CRT, while 27 patients underwent consecutive TACL with 3D-CRT (40-45 Gy for 4-5 weeks) that was started one week after the 1st TACL. The response was assessed by a computed tomography (CT) and the serum alpha-fetoprotein (AFP) level at 1-2 month intervals. Results: The objective response rates in the TACL group and TACL with 3D-CRT group were 18% and 48% at 3 months (P=0.051), and 10.5% and 42% at 6 months (P=0.024) respectively. The median survival time was 13 months and 13.5 months in TACL and TACL with 3D-CRT groups, respectively (P=0.502). The treatment response was better in the TACL with 3D-CRT group but there was no significant difference in survival between the two groups. Most toxicities in the two groups were mild, not exceeding grade 1 according to the WHO criteria. Conclusions: For patients with a huge HCC with PVTT, TACL with 3D-CRT achieved some meaningful clinical benefit. Prospective controlled trials will be needed to confirm the real benefit of TACL combined with 3D-CRT. (Korean J Hepatol 2007;13:378-386)

Citations

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    Chan-Kwon Park, Si-Hyun Bae, Hong-Jun Yang, Ho-Jong Chun, Il-Bong Choi, Jong-Young Choi, Seung-Kew Yoon
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    Jong Young Choi
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Case Report

Inflammatory Pseudotumor of the Liver
Sang Hyun Kim , Hyun Kyung Lee , Won Choong Choi , Kwan Yub Kim , Kyung Mi Park
Korean J Hepatol 1998;4(1):69-76.
Inflammatory pseudotumor of the liver is a rare benign tumor with microscopic finding of fibrous stroma and chronic inflammatory cell infiltration. Predominance of plasma cells, histiocytes, lymphocytes, some eosinophils and whorled pattern of fibrosis is often characteristic. Due to similar radiologic appearance of hepatocellular carcinoma, inflammatory pseudotumor of the liver was often misdiagnosed and hepatic resection is often performed before preoperative tissue diagnosis. We report a case of inflammatory pseudotumor, which was a 47-year-old woman with fever, upper aMominal pain and weight loss, diagnosed by sonoguided liver biopsy and treated with antibiotic therapy only without surgery. After two weeks of treatment, the radiologic image of the mass was almost disappeared with improvement of previous symptoms. This opportunity and the possible effectiveness of antibiotic treatment should keep in mind in the differential diagnosis of the hepatic mass with similar radiologic appearance of hepatocellular carcinoma. (Korean J Hepatol 1998;8:69 76)
  • 3,223 View
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Original Articles

Tumor Necrosis Factor-α and Interleukin-6 in Ascitic Fluid and Plasma in Spontaneous Bacterial Peritonitis
Moo In Park,Byung Cheol Song,Soo Hyun Yang,Han Chu Lee,Young Hwa Chung,Yung Sang Lee,Dong Jin Suh
Korean J Hepatol 1999;5(4):314-321.
Background/Aims
Spontaneous bacterial peritonitis (SBP) is a major problem associated with liver cirrhosis which has high mortality. Increased production of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) may be associated with development of renal impairment, one of the most important prognostic parameters in SBP. The aim of this study is to investigate the changes of these cytokines in ascitic fluid and plasma in patients with SBP and the relationship between these cytokines and development of renal impairment. Methods: Forty patients with liver cirrhosis and ascites were studied 21 with SBP and 19 with sterile ascites. TNF-α and IL-6 levels in ascitic fluid and plasma were determined by ELISA at the time of diagnosis in both groups and 48 hours after antibiotics treatment in SBP patients. Results: TNF- and IL-6 levels in ascitic fluid and plasma were significantly higher in patients with SBP than those without SBP (ascitic fluid TNF-α: 2.5±0.5 vs. 1.6±0.2; plasma TNF-α: 2.3±0.5 vs. 1.5±0.2; ascitic fluid IL-6: 3.8±0.5 vs. 3.0±0.4; plasma IL-6: 3.4±0.5 vs. 2.3±0.3, log pg/mL) (p<0.001). In patients with SBP, levels of TNF-α and IL-6 in ascitic fluid and plasma decreased 48 hours after antibiotics treatment. Eleven patients with SBP (11/21, 52%) developed renal impairment. Patients with renal impairment had significantly higher ascitic fluid and plasma TNF-α levels than those without renal impairment (median 2.5 vs. 2.1 for ascitic fluid, p=0.006; median 2.4 vs. 2.0, log pg/mL for plasma, p=0.04). Although four out of eleven (36%) patients who developed renal impairment died during hospitalization, all the patients without renal impairment survived (p=0.09). Conclusion: Our results suggest that the levels of TNF-α and IL-6 in ascitic fluid and plasma are increased in SBP and elevated levels of TNF-α in ascitic fluid and plasma may be associated with development of renal impairment, thus indicating poor prognosis in patients with SBP. (Korean J Hepatol 1999;5:314-321)
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Clinical Usefulness of PIVKA-II and Lens Culinaris Agglutinin-A Reactive Alpha-fetoprotein(AFP-L3) for the Diagnosis of Hepatocellular Carcinoma
B.H. Byun, Y.M. Park, S.H. Bae, J.Y. Choi, K.Y. Sung, S.H. Cho, N.I. Hahn, J.M. Yang, S.O. Choi, S.B. Cha, K.W. Chung, H.S. Sun, D.H. Park, B.S. Kim
Korean J Hepatol 2000;6(2):205-214.
Background/Aims
Des-γ-carboxy prothrombin(DCP), a protein induced by vitamin K absence or antagonist-II(PIVKA-II), and Lens culinaris agglutinin-A reactive AFP-L3 have been reported to be useful markers for the diagnosis of hepatocellular carcinoma (HCC). In the present study, both the PIVKA-II and AFP-L3 were analyzed and compared with a conventional AFP to determine its usefulness, specificity and sensitivity in the diagnosis of HCC. Methods: Sera were collected from 108 patients consisting of 17 patients with chronic hepatitis, 22 patients with liver cirrhosis and 69 patients with HCC. The AFP-L3 was determined by an lectin affinity electrophoresis coupled with an antibody-affinity blotting. Level of DCP was measured by an enzyme immunoassay with an anti-DCP monoclonal antibody. Results: The sensitivity and specificity of PIVKA-II and AFP L3 were 49.3% and 89.5%, and 32.5% and 85.7%, respectively. No significant correlation was found between the PIVKA-II or AFP L3 and serum AFP. No correlation was found between the PIVKA-II or AFP L3 and the characteristics of HCC. Conclusion: The determination of plasma DCP and AFP L3 levels combined with AFP levels may be useful especially for the differential diagnosis between HCC and chronic liver diseases without HCC.(Korean J Hepatol 2000;6:205-214)
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Case Report

A Case of Hepatic Carcinoid Tumor Regression with Octreotide
Hee-Jin Choi, M.D., Sang-Kyun Woo, M.D., Kyung-Hee Suh, M.D., Seung-Min Baek, M.D., Hyo-Jong Beak, M.D., Sang-Moon Lee, M.D., Won-Ho Kim, M.D., Sung-Ho Kim, M.D., Ik-Su Kim, M.D.*, Kyung-Rak Shon, M.D.*
Korean J Hepatol 2001;7(1):100-103.
Somatostatin analogue octreotide is commonly used for the treatment of carcinoid syndrome. Octreotide also has an antiproliferative effect in neuroendocrine tumors and has demonstrated tumor reduction in patients having advanced carcinoid tumor. This is a case report of a patient who had metastatic liver carcinoid tumor and showed marked regression of liver metastasis after octreotide therapy. (Korean J Hepatol 2001;7:100-103)
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Original Articles

Clinical Implication of Automatically Analysed AFP - L3 and PIVKA - 2 in the Diagnosis of Hepatocellular Carcinoma
Cheol Kim, M.D.*, Kwang Hyub Han, M.D.*, Yong Han Paik, M.D.*, Kun Hoon Song, M.D.*, Jae Yeon Jeong, M.D.*, Jeong Youp Park, M.D.*, Young Soo Park, M.D.*, Hyun Woong Lee, M.D.*, Tae Joo Jeon, M.D.*, Jae Yong Han, M.D.*, Kwan Sik Lee, M.D.*, Chae Yoon Chon, M.D.*, Young Myoung Moon, M.D.*, Kyoung Rhyul Lee, M.D.† , and Hyon Suk Kim, M.D.†
Korean J Hepatol 2001;7(4):467-474.
Background
/ Aims : Prothrombin induced by Vitamin K Antagonist-Ⅱ(PIVKA-Ⅱ)and alpha-fetoprotein(AFP)subtype reacting with Lens Culinaris Agglutinin(AFP-L3)are known as specific tumor markers for HCC. Recently a more sensitive ELA method for PIVKA-Ⅱand an automatic analyzer with Liquid Phase Binding Assay method(LBA method)for AFP-L3 have been developed. The aim of this study was to evaluate the feasibility of PIVKA-Ⅱ and AFP-L3 measured by newly developed methods as complementary tumor markers to AFP in the diagnosis of HCC. Methods : The serum concentration of AFP, PIVKA-Ⅱ, and a fraction of AFP-L3 were determined from 188 patients with HCC and 118 patients with various liver diseases including tumors of the liver. AFP was measured by EIA, PIVKA-Ⅱ by sensitive EIA, and AFP-L3 by the LBA method with LiBASys Auto-analyzer. The cutoff values for AFP, PIVKA-Ⅱ, AND AFP-L3 WERE 400ng/mL, 40 Mau/mL, AND 15%, respectively. Results : The sensitivity and specificity of serum PIVKA-Ⅱwere 69.2% and 76.5%, respectively. Sixty-two(51.2%) of 121 patients with HCC, in which AFP was less than 400ng/mL were PIVKA-Ⅱ positive. The specificity and specificity of serum AFP-L3 were 48.8% and 90.8%, respectively. When AFP-L3 was used in combination with PIVKA-Ⅱ,31(46.3%) of the 67 patients with small less than 3cm HCC were positive for at least one of these markers. Conclusion : PIVKA-Ⅱ measures by sensitive EIA may be useful for the diagnosis of HCC with low AFP level. AFP-L3 and PIVKA-Ⅱ may improve the detection rate of small HCCs less than 3cm. (Korean J Hepatol 2001;7 :467- 474)
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Clinical Efficacy of Serum PIVKA-2 in the Diagnosis and Follow up after Treatment of Hepatocellular Carcinoma
Young Joon Yoon, M.D., Kwang-Hyub Han, M.D., Chul Kim, M.D., Chae Yoon Chon, M.D., Young Myoung Moon, M.D., Chang Hoon Han, M.D., Hye Jin Choi, M.D., Yong Soo Kim, M.D., Jae Yong Han, M.D. and Hyon Suk Kim, M.D.†
Korean J Hepatol 2002;8(4):465-471.
Background/Aims
Protein induced by vitamin K absence or antagonist II (PIVKA-II) appears to be a useful tumor marker for the evaluation of patients with hepatocellular carcinoma (HCC). But the usefulness of PIVKA-II was not yet clear in Korea where hepatitis B-virus is endemic. We investigated the usefulness of PIVKA-II in the diagnosis and follow-up after treatment of HCC. Methods: We studied patients with HCC which was pathologically confirmed. PIVKA-II was measured by enzyme immunoassay. PIVKA-놳 levels before and after treatment, in correlation with imaging studies, were analyzed for the comparison of treatment responses. Kappa index was obtained. Results: A total of 129 patients were included. 93 patients (72%) were HBsAg positive. 86 patients (67%) were PIVKA-II >40 mAU/mL. 52 patients (40%) were AFP >20 ng/mL and 77 patients (60%) were AFP 20 ng/mL. Of 77 patients, 40 patients (52%) showed PIVKA-II >40 mAU/mL. 68 of 129 patients were evaluated treatment response. On the basis of radiologic response, CR was 33, PR 17, SD 12, and PD 6. Of the 33 radiologic CR patients, 30 patients were CR and 3 patients were PR by means of PIVKA-II response. Of the 17 radiologic PR patients, 6 patients were CR and 7 patients were PR. Therefore, tumor responses by radiologic and PIVKA-II were well correlated (Kappa index was 0.59). Conclusions: PIVKA-II can be used as a useful tumor marker for patients with HCC, especially those with low levels of AFP, before and after treatment in Korea. (Korean J Hepatol 2002;8:465-471)
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Hepatology Elsewhere

Topics Related to Hepatocellular Carcinoma
Il Han Song
Korean J Hepatol 2004;10(2):174-176.
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Liver Pathology

Inflammatory Pseudotumor of the Liver
So Young Jin
Korean J Hepatol 2005;11(1):90-93.
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Case Reports

Four Cases of Hepatic Fascioliasis Mimicking Cholangiocarcinoma
Yong Hoon Kim, M.D., Koo Jeong Kang, M.D. and Jung Hyeok Kwon, M.D.1
Korean J Hepatol 2005;11(2):169-175.
Human fascioliasis is a zoonosis caused by Fasciola hepatica, and this is a trematode that infests cattle and sheep. Humans are accidental hosts in the life cycle of this parasite. People are infected by ingestion of the water or the raw aquatic vegetables that are contaminated with the metacercaria. This fluke’s worldwide distribution occurs in areas where sheep, cattle and goats are raised, and there is a life-cycle niche for this fluke in lymnaeid snails. However, it is a rare disease in Korea. We experienced four human fascioliasis which were difficult to differentiate from hepatic malignancy in three patients, and this was misdiagnosed as common hepatic duct tumor in one patient. The patients manifested only vague abdominal symptoms. Intrahepatic fascioliasis showed multiple ill-defined hypoattenuating lesions and filling defects of the lesion lumens on radiologic study. A striking eosinophilia from the patients’ blood was identified and a positive finding of a serum enzyme linked immunosorbent assay for the Fasciola hepatica was also noted in three of four patients. The therapeutic trial with triclabendazole and praziquantel was not successful. (Korean J Hepatol 2005;11:169-175)
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Infarction and Perforation of the Small Intestine due to Tumor Emboli from Disseminated Rectal Cancer
Jae Cheol Jo , Dae Ho Lee , Ho June Song , Sang We Kim , Cheol Won Suh , Yoon Koo Kang
Korean J Hepatol 2008;12(2):130-132.
Small bowel perforation due to hematogenous metastatic tumor emboli is a rare event, especially in a patient with rectal cancer. We report a 75-year-old man with relapsed rectal cancer who developed an acute abdomen, which was found to be due to a perforated terminal ileum. Emergency surgery involved segmental resection and ileostomy. The pathology of the resected small bowel showed multifocal and extensive metastatic tumor emboli in the entire wall, leading to transmural infarction followed by perforation, without a discrete tumor mass. The pathology with immunohistochemistry showed a rectal tumor that was positive for CK-20 but negative for CK-7 and TTF-1. This extremely rare complication of rectal cancer resulted from ischemia and infarct caused by disseminated metastatic tumor emboli without direct invasion or mass formation.
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Editorial
PIVKA-II as a Serological Marker of Hepatocellular Carcinoma
Sook-Hyang Jeong
Korean J Hepatol 2006;12(3):315-317.
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