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"Alpha-fetoprotein"

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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.

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  • 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
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Hepatic neoplasm

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region
Do Young Kim, Bao Nguyen Toan, Chee-Kiat Tan, Irsan Hasan, Lyana Setiawan, Ming-Lung Yu, Namiki Izumi, Nguyen Nguyen Huyen, Pierce Kah-Hoe Chow, Rosmawati Mohamed, Stephen Lam Chan, Tawesak Tanwandee, Teng-Yu Lee, Thi Thanh Nguyen Hai, Tian Yang, Woo-Chang Lee, Henry Lik Yuen Chan
Clin Mol Hepatol 2023;29(2):277-292.
Published online January 30, 2023
DOI: https://doi.org/10.3350/cmh.2022.0212
Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Citations

Citations to this article as recorded by  Crossref logo
  • Emerging evidence supports direct-acting antiviral therapy for HCC patients beyond the early stage: Correspondence to editorial on “Direct-acting antiviral therapy for patients with HCV-related hepatocellular carcinoma: A nationwide cohort study”
    Teng-Yu Lee, Pei-Chien Tsai, Shou-Wu Lee, Ming-Lung Yu
    Clinical and Molecular Hepatology.2026; 32(1): e68.     CrossRef
  • Digital pathology-based prognostic model for hepatocellular carcinoma: Integrating pathomics signatures with clinical parameters for recurrence prediction and biological interpretation
    Qi Wang, Yuxi Huang, Yu Zhang, Yu Zhu, Peng Hu, Yongfu Xu, Zhen-yu Jiang, Long Liu, Shao-wei Li
    Computer Methods and Programs in Biomedicine.2026; 275: 109180.     CrossRef
  • Serum Outperforms Plasma for Glypican-3 Quantification in Hepatocellular Carcinoma—A Prospective Comparative Study
    Ming-Tze Yang, Jiunn-Min Wang, Chen-Shiou Wu, Shou-Wu Lee, Hsin-Ju Tsai, Chia-Chang Chen, Ying-Cheng Lin, Hui-Fen Liu, Teng-Yu Lee
    Journal of Clinical Medicine.2026; 15(2): 448.     CrossRef
  • Integrated spatial and single-cell transcriptomics reveals RPL8 as a prognostic biomarker and therapeutic target in hepatocellular carcinoma
    Jinna Tan, Junzhu Liang, Yaoyang Li, Jiaqian He, Hui Yin, Hemeng Wu, Yuzhen Luo, Mingfen Li, Fuli Long, Hongsheng Lin
    Translational Oncology.2026; 64: 102663.     CrossRef
  • Risk Scores for Stratifying Hepatocellular Carcinoma and Optimizing Surveillance Strategies
    Yu-Ping Chang, Yun-Chu Chen, Chen-Hua Liu
    Cancers.2026; 18(1): 158.     CrossRef
  • Diagnostic Performance Comparison of AFP, PIVKA-II, GALAD Model, and ASAP Model Across Two Chemiluminescence Immunoassay Platforms for Hepatocellular Carcinoma
    Yuan Huang, Rui Ding, Yue Cui, Peng Li, Jie Niu, Guan-Hua Wang, Xu-Zhen Qin
    Journal of Hepatocellular Carcinoma.2026; Volume 13: 1.     CrossRef
  • Development and validation of the APTNM staging system: Integration of serum biomarkers with TNM classification for enhanced prognostic stratification following hepatectomy for hepatocellular carcinoma
    Xin Li, Yi-Fei Liu, Chen-Yao Zhou, Jun Lu, Guo-Wei Wang, Zi-Jie Tang, Zi-Chao Tu, Yong-Yi Zeng, Wei Guo, Ji-Li Li, Jia-Hao Xu, Chao Li, Ming-Da Wang, Feng Shen, Fei Wu, Tian Yang
    European Journal of Surgical Oncology.2026; 52(2): 111384.     CrossRef
  • Artificial Intelligence Applications in the Diagnosis, Treatment, and Prognosis of Hepatocellular Carcinoma
    Ming-Ying Lu, Jacky Chung-Hao Wu, Henry Horng-Shing Lu, Mohammed Eslam, Ming-Lung Yu
    Gut and Liver.2026; 20(1): 5.     CrossRef
  • Comparison of diagnostic performance of GAAD, GALAD, and ASAP scores for detecting hepatocellular carcinoma in advanced liver fibrosis patients
    Alberto Izquierdo-Martínez, Ángela Rojas, Ricardo Rubio-Sánchez, Inmaculada Dominguez-Pascual, Manuel Romero-Gómez, Daniel Fatela-Cantillo
    Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2026;[Epub]     CrossRef
  • 68Ga-FAPI-04 PET/CT in the Diagnosis of Hepatocellular Carcinoma Associated with Cirrhosis: Diagnostic Value, Correlation Between PET Parameters of the Tumor and Its Size, and PIVKA-II Levels
    Zhamilya Zholdybay, Zhanar Zhakenova, Bekzhan Issamatov, Madina Gabdullina, Yevgeniya Filippenko, Suriya Yessentayeva, Galymzhan Alisherov, Jandos Amankulov, Ildar Fakhradiyev
    Diagnostics.2026; 16(2): 249.     CrossRef
  • Surveillance for Hepatocellular Carcinoma in Cirrhosis: End of Monopoly for Serum Alpha Fetoprotein
    Lung-Yi Mak, Man-Fung Yuen
    Gastroenterology.2025; 168(2): 217.     CrossRef
  • Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies
    Jinlin Hou, Thomas Berg, Arndt Vogel, Teerha Piratvisuth, Jörg Trojan, Enrico N. De Toni, Masatoshi Kudo, Katarina Malinowsky, Peter Findeisen, Johannes Kolja Hegel, Wenzel Schöning, Kairat Madin, Konstantin Kroeniger, Henry Lik-Yuen Chan, Ashish Sharma
    JHEP Reports.2025; 7(2): 101263.     CrossRef
  • Establishment of sex-specific reference intervals for PIVKA-II in Southwest China: A real-world data analysis
    Bin Wei, Yalin Zheng, Lixin Li, Limei Luo, Ying Guo
    Annals of Clinical Biochemistry: International Journal of Laboratory Medicine.2025; 62(3): 202.     CrossRef
  • Comparative Validation of Prediction Models for HCC Outcomes in Living Donor Liver Transplantation: Superiority of Tumor Markers to Imaging Study
    Hwa‐Hee Koh, Minyu Kang, Deok‐Gie Kim, Jae Hyon Park, Eun‐Ki Min, Jae Geun Lee, Myoung Soo Kim, Dong Jin Joo
    Journal of Gastroenterology and Hepatology.2025; 40(3): 626.     CrossRef
  • Rapid evaluation of hepatocellular carcinoma by detecting plasma exosomes with time-resolved fluorescence immunochromatographic test strips
    Jiaming Li, Jianfen Su, Minghui Li, Yaofen Wu, Huiqiang Chen, Xihua Fu, Hongliang Yao, Jinping Chen, Yuntao Liu, Jie Zan
    Microchimica Acta.2025;[Epub]     CrossRef
  • Prognostic Value of the ASAP Score for Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma: A Multicenter Analysis of 1,239 Patients
    Tian Yang, Dong-Xu Yin, Yong-Kang Diao, Ming-Da Wang, Xian-Ming Wang, Yong-Yi Zeng, Zhong Chen, Han Liu, Fu-Jie Chen, Yu-Chen Li, Jia-Hao Xu, Han Wu, Lan-Qing Yao, Xin-Fei Xu, Chao Li, Li-Hui Gu, Alfred W. Chieh Kow, Timothy M. Pawlik, Feng Shen
    Journal of Clinical and Experimental Hepatology.2025; 15(3): 102497.     CrossRef
  • Predicting hepatocellular carcinoma outcomes and immune therapy response with ATP-dependent chromatin remodeling-related genes, highlighting MORF4L1 as a promising target
    Chao Xu, Litao Liang, Guoqing Liu, Yanzhi Feng, Bin Xu, Deming Zhu, Wenbo Jia, Jinyi Wang, Wenhu Zhao, Xiangyu Ling, Yongping Zhou, Wenzhou Ding, Lianbao Kong
    Cancer Cell International.2025;[Epub]     CrossRef
  • Cluster analysis of hepatocellular carcinoma prognosis using preoperative alpha-fetoprotein and des-gamma-carboxy prothrombin levels: a multi-institutional study
    Yoshitaka Saegusa, Yuki Imaoka, Masahiro Ohira, Tsuyoshi Kobayashi, Naruhiko Honmyo, Michinori Hamaoka, Takashi Onoe, Daisuke Takei, Koichi Oishi, Tomoyuki Abe, Toshihiro Nakayama, Miho Akabane, Kazunari Sasaki, Hideki Ohdan
    Journal of Gastrointestinal Surgery.2025; 29(4): 101980.     CrossRef
  • 3D synergistic tumor-liver analysis further improves the efficacy prediction in hepatocellular carcinoma: a multi-center study
    Yurong Jiang, Jiawei Zhang, Zhaochen Liu, Jinxiong Zhang, Xiangrong Yu, Danyan Lin, Dandan Dong, Mingyue Cai, Chongyang Duan, Shuyi Liu, Wenhui Wang, Yuan Chen, Qiyang Li, Weiguo Xu, Meiyan Huang, Sirui Fu
    BMC Cancer.2025;[Epub]     CrossRef
  • Teaching design for chapter “primary liver cancer” in surgery course based on the clinical theory and clerkship synchronization model in the era of New Medicine
    Feng Ye, Qiang Cai, Xiaoyong Gong, Jiajun Ren, Ruixin Sun, Chang Liu, Xiaoli Wang, Yuan Qiao
    Global Medical Education.2025; 2(1): 149.     CrossRef
  • Development and validation of a new prognostic tool for hepatocellular carcinoma undergoing resection: The Weighted Alpha-Fetoprotein Tumor Burden Score (WATS)
    Tonghui Lu, Kailing Xie, Yan Chen, Mingxiu Ma, Yaming Guo, Tianqiang Jin, Chaoliu Dai, Feng Xu
    European Journal of Surgical Oncology.2025; 51(6): 109677.     CrossRef
  • Divergent trends in cirrhosis and liver cancer highlight the ongoing efforts required for hepatitis elimination
    Grace Lai-Hung Wong, Henry Lik-Yuen Chan
    Hepatology.2025; 82(5): 1056.     CrossRef
  • CA19-9, CEA and PIVKA-Ⅱ as a novel panel of serum markers for diagnosis of pancreatic cancer
    Meifang Wang, Hongying Bu, Weijia Luo, Xi Zeng, Guodong Chen, Yingchun He, Deliang Cao
    Clinical Biochemistry.2025; 137: 110902.     CrossRef
  • Tumor burden score combined with AFP and PIVKA-II (TAP score) to predict the prognosis of hepatocellular carcinoma patients after radical liver resection
    Zhan-Cheng Qiu, You-Wei Wu, Jun-Long Dai, Wei-Li Qi, Chu-Wen Chen, Yue-Qing Xu, Jun-Yi Shen, Chuan Li, Tian-Fu Wen
    Langenbeck's Archives of Surgery.2025;[Epub]     CrossRef
  • The Diagnostic Performance of AFP, AFP-L3, DCP, CA199, and Their Combination for Primary Liver Cancer
    Yue Liu, Wenrong Jiang, Xiangxiao Li, Hu Zhao, Shiwen Wang
    Journal of Hepatocellular Carcinoma.2025; Volume 12: 513.     CrossRef
  • 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation
    Danjun Song, Zhou Zhang, Jiaping Zheng, Wei Zhang, Jiabin Cai
    Biomarker Research.2025;[Epub]     CrossRef
  • Des-γ-carboxy Prothrombin in hepatocellular carcinoma post-operative recurrence risk evaluation
    Xinting Pan, Yang Zhou, Zhenli Li, Pengfei Guo, Jianyang Zeng, Xiuqing Dong, En Hu, Liman Qiu, Zhixiong Cai, Geng Chen, Xiaolong Liu
    Communications Medicine.2025;[Epub]     CrossRef
  • Assessing the Validity of the AASLD Surgical Treatment Algorithm in Patients with Early-Stage Hepatocellular Carcinoma
    Aryoung Kim, Byeong Geun Song, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Myung Ji Goh, Dong Hyun Sinn
    Gut and Liver.2025; 19(2): 265.     CrossRef
  • Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
    Meng Sha, Jun Wang, Jie Cao, Zhi-Hui Zou, Xiao-ye Qu, Zhi-feng Xi, Chuan Shen, Ying Tong, Jian-jun Zhang, Seogsong Jeong, Qiang Xia
    Clinical and Molecular Hepatology.2025; 31(Suppl): S285.     CrossRef
  • Key prognostic factors in transarterial chemoembolization combined with sorafenib treatment for hepatocellular carcinoma with portal vein tumor thrombosis
    Zilun Lei
    American Journal of Cancer Research.2025; 15(2): 517.     CrossRef
  • tRF-23-R9J89O9N9:A novel liquid biopsy marker for diagnosis of hepatocellular carcinoma
    Kangfeng Jin, Zhiyun Mao, Yelan Tang, Wei Feng, Shaoqing Ju, Rongrong Jing, Jianhui Chen, Wei Zong
    Clinica Chimica Acta.2025; 572: 120261.     CrossRef
  • Cost‐Effective Identification of Hepatocellular Carcinoma from Cirrhosis or Chronic Hepatitis Virus Infection Using Eight Methylated Plasma DNA Markers
    Tian Yang, Mingda Wang, Nanya Wang, Mingxin Pan, Yu Xu, Qiancheng You, Lanqing Yao, Jiahao Xu, Lihui Gu, Xiaodong Sun, Lei Zhang, Jiayue Xu, Bingsi Li, Guoqiang Wang, Shangli Cai, Guoyue Lv, Feng Shen
    Advanced Science.2025;[Epub]     CrossRef
  • Paracancerous binuclear hepatocytes assessed by computer program is a novel biomarker for short term recurrence of hepatocellular carcinoma after surgery
    Yifan Zhang, Yiquan Lu, Nan Wang, Fengjie Hao, Yongjun Chen, Xiaochun Fei, Junqing Wang
    Scientific Reports.2025;[Epub]     CrossRef
  • Preoperative identification of hepatocellular carcinoma from focal liver lesions ≤ 20 mm in high-risk patients using clinical and contrast-enhanced ultrasound features
    Xin-Yuan Hu, Yi-Kang Sun, Yao Miao, Xiao-Ling Chen, Dan Lu, Bo-Yang Zhou, Li-Fan Wang, Chong-Ke Zhao, Hao-Hao Yin, Xiao-Long Li, Zi-Tong Chen, Ya-Qin Zhang, Ming-Rui Zhu, Xin Guan, Er-Xuan Wu, Hong Han, Li-Ping Sun, Qing Lu, Hui-Xiong Xu
    European Journal of Radiology.2025; 187: 112076.     CrossRef
  • Plasma methylated HIST1H3G as a non-invasive biomarker for diagnostic modeling of hepatocellular carcinoma
    Weiwei Zhu, Huifen Wang, Yudie Cai, Jun Lei, Jia Yu, Ang Li, Zujiang Yu
    Frontiers in Medicine.2025;[Epub]     CrossRef
  • Postoperative regular follow-up in hepatocellular carcinoma: Transforming early detection into survival gains
    Alfred Wei Chieh Kow
    Hepatobiliary & Pancreatic Diseases International.2025; 24(3): 237.     CrossRef
  • New insights into biomarkers and risk stratification to predict hepatocellular cancer
    Katrina Li, Brandon Mathew, Ethan Saldanha, Puja Ghosh, Adrian R. Krainer, Srinivasan Dasarathy, Hai Huang, Xiyan Xiang, Lopa Mishra
    Molecular Medicine.2025;[Epub]     CrossRef
  • The immune-reinforcements of Lenvatinib plus anti-PD-1 and their rationale to unite with TACE for unresectable hepatocellular carcinoma treatment
    Jiayun Jiang, Hui Zhang, Yanjiao Ou, Jiejuan Lai, Yulan Huang, Wenyun Cai, Chong Li, Leida Zhang, Yu Fu
    Immunology Letters.2025; 275: 107003.     CrossRef
  • HES V2.0 surpasses GALAD for HCC detection: a review of multi-dimensional biomarker scores and studies
    Fouad Jaber, Hashem B. El-Serag
    Hepatic Oncology.2025;[Epub]     CrossRef
  • Integrated spatial and single cell transcriptomics identifies PRKDC as a dual prognostic biomarker and therapeutic target in hepatocellular carcinoma
    Wenpeng Pang, Yunyong Wang, Xiaohang Lu, Minpeng Li, Fuli Long, Songlin Chen, Yuan Yu, Mingfen Li, Hongsheng Lin
    Scientific Reports.2025;[Epub]     CrossRef
  • Hepatocellular Carcinoma: The Search for an Optimal Screening Test
    Sara Haj Ali, Shahd I Alqato, Amjad M Almansi, Noor S Haj Ali, Mohammad A Amaireh
    Middle East Journal of Digestive Diseases.2025; 17(1): 31.     CrossRef
  • Invited commentary on “Tumor biology characteristics score based on alpha-fetoprotein and prothrombin induced by vitamin K absence-II predicts recurrence and survival after curative resection for hepatocellular carcinoma: a multicenter cohort study”
    Abu Bakar Hafeez Bhatti
    Journal of Gastrointestinal Surgery.2025; 29(7): 102076.     CrossRef
  • Development of a chitosanase 3-like protein 1 assay kit and study of its application in patients with hepatocellular carcinoma
    Min Liu, Yanru Qiu, Erfu Xie, Pu Qian, Shuxian Yang, Simin Zhao, Wenjun Yan, Xuan Huang, Shuang Han
    BMC Biotechnology.2025;[Epub]     CrossRef
  • Predictability of clinical outcomes after external beam radiotherapy for hepatocellular carcinoma according to tumor marker dynamics
    Sunmin Park, Chai Hong Rim, Young Kul Jung, Hyung Joon Yim, Hwan Hoon Chung, Won Sup Yoon, Gregory Tiao
    PLOS One.2025; 20(5): e0323450.     CrossRef
  • Tumor marker pseudoprogression and immune-related cholangitis during conversion therapy for massive hepatocellular carcinoma: a case report
    Xiaodong Zhang, Luyi Zhang, Shuangying Zhao, Lingling Dai, Huayu Li, Xudong Wu, Huanjun Yan, Rongfeng Lin, Kelei Zhu
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Current and new strategies for hepatocellular carcinoma surveillance
    Natchaya Polpichai, Chongkonrat Maneenil, Pojsakorn Danpanichkul, Chitchai Rattananukrom, Ashok Choudhury, Yu Jun Wong, Pimsiri Sripongpun, Suthat Liangpunsakul, Apichat Kaewdech
    Gastroenterology Report.2025;[Epub]     CrossRef
  • Alpha-fetoprotein: A Multifaceted Player in Cancer Biology
    Mete Ucdal, Yigit Yazarkan, Gamze Sonmez, Basak Celtikci, Yasemin Balaban
    Euroasian journal of hepato-gastroenterology.2025; 15(1): 72.     CrossRef
  • Erratum to “Cluster analysis of hepatocellular carcinoma prognosis using preoperative alpha-fetoprotein and des-gamma-carboxy prothrombin levels: a multi-institutional study” [J Gastrointest Surg 29 (2025) 101980]
    Yoshitaka Saegusa, Yuki Imaoka, Masahiro Ohira, Tsuyoshi Kobayashi, Naruhiko Honmyo, Michinori Hamaoka, Takashi Onoe, Daisuke Takei, Koichi Oishi, Tomoyuki Abe, Toshihiro Nakayama, Miho Akabane, Kazunari Sasaki, Hideki Ohdan
    Journal of Gastrointestinal Surgery.2025; 29(8): 102129.     CrossRef
  • Hepatocellular Carcinoma: Review of Indian Literature
    Vaishnavi Konda, Shanthi Vijayaraghavan
    Gastroenterology, Hepatology and Endoscopy Practice.2025; 5(3): 95.     CrossRef
  • Long-Term Prognostic Value of AFP and PIVKA-II in HCC After Living Donor Liver Transplantation: A Single-Center Retrospective Study
    Saran Ochir Gongor, YoungRok Choi, Gayoung Kim, Min Kyoung Kim, Sang Hyuk Park, Jiyoung Kim, Jae-Yoon Kim, Su young Hong, Jeong-Moo Lee, Suk Kyun Hong, Kwang-Woong Lee
    Transplant International.2025;[Epub]     CrossRef
  • Prothrombin-induced by vitamin K absence II as a prognostic factor in living donor liver transplantation for hepatocellular carcinoma
    Abu Bakar Hafeez Bhatti, Usman Shafique, Nazish Ahmed, Ghazanfar Abbas, Muslim Atiq, Haseeb Haider Zia, Nusrat Yar Khan, Atif Rana
    Scientific Reports.2025;[Epub]     CrossRef
  • Evaluation of serum hsa_tsr014055 as a potential biomarker for diagnosis and prognosis of hepatocellular carcinoma
    Jing Xu, Bairong Chen, Jing Qi, Jinran Wu, Wei Feng, Kangfeng Jin, Hongyi Bao, Lin Chen, Feng Wang
    Annals of Medicine.2025;[Epub]     CrossRef
  • Global, regional, and national burden of liver cancer due to hepatitis B, 1990–2021 and projections to 2051: a systematic analysis of the Global Burden of Disease Study 2021
    Peipei Yang, Wenjie Huang, Yuanyuan Xu, Qiurong Li, Xinyan Shu, Jiaqian Zuo, Wenqin Ren, Yujie Huang, Yuhao Teng, Peng Shu
    European Journal of Gastroenterology & Hepatology.2025;[Epub]     CrossRef
  • Differential Associations of PIVKA-II with Epithelial and Mesenchymal Features in HCC and PDAC
    Antonella Farina, Gaia Cicolani, Valentina Viggiani, Matteo Maini, Antonio Angeloni, Emanuela Anastasi
    International Journal of Molecular Sciences.2025; 26(15): 7581.     CrossRef
  • Preoperative ASAP score predicts recurrence and survival following curative hepatic resection for hepatitis B virus-related hepatocellular carcinoma: A multicenter cohort study
    Dongxu Yin, Zixuan Wang, Chao Li, Huixuan Fan, Zichao Tu, Yongkang Diao, Zijie Tang, Yongyi Zeng, Han Wu, Lihui Gu, Lanqing Yao, Xinfei Xu, Feng Shen, Mingda Wang, Tian Yang
    European Journal of Surgical Oncology.2025; 51(10): 110361.     CrossRef
  • Sex disparity in hepatocellular carcinoma recurrence after curative liver resection: a multicenter comprehensive analysis
    Mu-Gen Dai, Si-Yu Liu, Qing Xu, Wen-Feng Lu, Lei Liang, Jun-Wei Liu, Kun Zhang, Bin Ye
    European Journal of Gastroenterology & Hepatology.2025; 37(11): 1275.     CrossRef
  • Clinical performance of GAAD score, alpha-fetoprotein, and PIVKA-II in diagnosing hepatocellular carcinoma in the Vietnamese cohort
    Thuy Thi Thu Pham, Dat Tan Ho, Toan Bao Nguyen, Hai Thanh Phan
    Discover Oncology.2025;[Epub]     CrossRef
  • CRAFITY and AFP/PIVKA-II Kinetics Predict Prognosis in Hepatocellular Carcinoma on Immunotherapy
    Shou-Wu Lee, Yi-Jie Huang, Ying-Cheng Lin, Hsin-Ju Tsai, Chia-Chang Chen, Chung-Hsin Chang, Teng-Yu Lee, Yen-Chun Peng
    Cancers.2025; 17(18): 3058.     CrossRef
  • Targeting glypican-3 as a new frontier in liver cancer therapy
    Chen-Shiou Wu, Teng-Yu Lee, Hsu-Wen Chao
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Early PIVKA-II Response Associated with Treatment Efficacy and Survival Outcomes for Patients with Advanced Hepatocellular Carcinoma Receiving Immune Checkpoint Inhibitors and Targeted Therapy
    Zheng-Kang Fang, Yu-Ting Xiao, Xia Feng, Zhe-Jin Shi, Si-Yu Liu, Yang Yu, Li-Ming Jin, Dong-Sheng Huang, Cheng-Wu Zhang, Jun-Wei Liu, Lei Liang
    Journal of Hepatocellular Carcinoma.2025; Volume 12: 2235.     CrossRef
  • Nanomaterial-Mediated Electrochemical and Optical Biosensors and Their Application in Tumour Marker Detection
    Xinlan Wang, Jingyi Hei, Tao Zhao, Xiyu Liu, Yong Huang
    Sensors.2025; 25(18): 5902.     CrossRef
  • Combined Analysis of Protein Induced by Prothrombin Induced by Vitamin K Absence (PIVKA) and Alpha-L-Fucosidase (AFU) with Alpha-Fetoprotein (AFP) May Improve the Diagnostic Efficacy for Liver Cirrhosis and Hepatocellular Carcinoma in Chronic Hepatitis B
    Haisong Hou, Ruiqiang Weng, Liu Liang, Wendao Han
    International Journal of General Medicine.2025; Volume 18: 6031.     CrossRef
  • Leveraging artificial intelligence to validate traditional biomarkers and drug targets in liver cancer recovery: a mini review
    Shengjian Wu, Xiaoqiao Chen, Yuxiu Ji, Chi Zhang, Yujie Xie, Bin Liang
    Frontiers in Pharmacology.2025;[Epub]     CrossRef
  • Pilot Study of PIVKA-II in the Prognostic Assessment of Hepatocellular Carcinoma in Chronic Viral Hepatitis: Comparative Findings from HBV and HCV Cohorts from a Single Center in Serbia
    Ivana Milošević, Nataša Nikolić, Sanja Stanković, Ana Filipović, Jovana Ranin, Irena Paunović, Jelena Simić, Branko Beronja
    Biomedicines.2025; 13(11): 2653.     CrossRef
  • Clinical Implications and Novel Insights into Adolescent Primary Liver Cancer: A Nightmare for Adolescents?
    Huidong Guo, Xiaojun Chen, Rong Li, Jianzhen Shen, Donghui Gan, Yue Yin, Hehui Zhang, Jiachen Xie, Longfei Xie, Yanquan Liu
    Journal of Hepatocellular Carcinoma.2025; Volume 12: 2513.     CrossRef
  • MRI-based 2.5D deep learning and radiomics effectively predicted microvascular invasion and Ki-67 expression in hepatocellular carcinoma
    Hongmei Yu, Depeng Kong, Xiaojun Mo, Ju Huang, Jie Wu, Yang Wang, Feizhou Du, Nima Broomand Lomer,
    PLOS One.2025; 20(11): e0336579.     CrossRef
  • 5’-transfer RNA halve-lysine-CTT as a promising biomarker for early detection of hepatocellular carcinoma
    Jie Yuan, Wen-Chao Gu, Tian-Xin Xu, Xian-Juan Shen, Xian Li, Lei Shen, Yan Zhang, Shao-Qing Ju
    World Journal of Gastrointestinal Oncology.2025;[Epub]     CrossRef
  • Protein Induced by Vitamin K Absence or Antagonist‐II: Significantly Elevated in Obstructive Jaundice and Sepsis Patients Without Hepatocellular Carcinoma
    Ke Zhang, Xiarui Ye, Xianran Fu
    Journal of Clinical Laboratory Analysis.2025;[Epub]     CrossRef
  • Rapid Detection and Purification of Extracellular Vesicles for Hepatocellular Carcinoma Screening Using a Plasmonic Metasurface Integrated with the Kolmogorov–Arnold Network
    Jiaheng Zhu, Chenhongmei Wang, Tianhao Huang, Lihuang Zeng, Qiang Niu, Xinyue Huang, Hanyang Chen, Mengqi Jiang, Baichang Deng, Yiming Yan, Xiaohui Liu, Junjie Chen, Yinong Xie, Jiaqing Shen, Wei Chen, Yuan Gao, Kaibin Chen, Xiangyujie Lin, Lijun Zeng, Bo
    ACS Nano.2025; 19(49): 41557.     CrossRef
  • Early screening for liver cancer must be performed
    Zi-Han Liu, Wen-Jun Wang, Shuang-Suo Dang
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Adjuvant Sintilimab with or without Anti-VEGF Therapy After Resection in Hepatocellular Carcinoma with Microvascular Invasion: A Multicenter Retrospective Study
    Kang Wang, Yan-Jun Xiang, Hong-Ming Yu, Yu-Qiang Cheng, Yi-Tao Zheng, Yun-Feng Shan, Shu-Qun Cheng
    Journal of Hepatocellular Carcinoma.2025; Volume 12: 2735.     CrossRef
  • Exosomal microRNAs in Hepatocellular Carcinoma: Diagnostic and Prognostic Applications
    Sarang Kim, Nayeon Gu, Tae-Su Han
    Convergence Hepatology.2025; 1(1): 44.     CrossRef
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Viral hepatitis

Novel biomarkers for the management of chronic hepatitis B
Takako Inoue, Yasuhito Tanaka
Clin Mol Hepatol 2020;26(3):261-279.
Published online June 15, 2020
DOI: https://doi.org/10.3350/cmh.2020.0032
Hepatitis B virus (HBV) cannot be eliminated completely from infected hepatocytes because of the presence of intrahepatic covalently closed circular DNA (cccDNA). As chronic hepatitis B (CHB) can progress to cirrhosis and hepatocellular carcinoma (HCC), it is important to manage CHB to prevent HCC development in high-risk patients with high viral replicative activity or advanced fibrosis. Serum biomarkers are noninvasive and valuable for the management of CHB. Hepatitis B core-related antigen (HBcrAg) correlates with serum HBV DNA and intrahepatic cccDNA. In CHB patients with undetectable serum HBV DNA or loss of HBsAg, HBcrAg still can be detected and the decrease in HBcrAg levels is significantly associated with hopeful outcomes. Therefore, HBcrAg can predict HCC occurrence or recurrence. Measurement of the Mac-2 binding protein glycosylation isomer (M2BPGi) has been introduced for the evaluation of liver fibrosis. Because elevated M2BPGi in CHB is related to liver fibrosis and the prediction of HCC development, monitoring its progression is essential. Because alpha fetoprotein (AFP) has insufficient sensitivity and specificity for early-stage HCC, a combination of AFP plus protein induced by vitamin K absence factor II, or AFP plus Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein might improve the diagnosis of HCC development. Additionally, Dickkopf-1 and circulating immunoglobulin G antibodies are the novel markers to diagnose HCC or assess HCC prognosis. This review provides an overview of novel HBV biomarkers used for the management of intrahepatic viral replicative activity, liver fibrosis, and HCC development.

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Original Article

Hepatic neoplasm

Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis
Yejoo Jeon, Eun Sun Jang, Yun Suk Choi, Jin-Wook Kim, Sook-Hyang Jeong
Clin Mol Hepatol 2016;22(3):359-365.
Published online September 25, 2016
DOI: https://doi.org/10.3350/cmh.2016.0033
Background/Aims
Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC.
Methods
We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve.
Results
Plasma GPC3 levels in HCC patients were very low (0–3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729.
Conclusions
The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted.

Citations

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Case Report

Benign liver tumors and cystic disease of liver

Intrahepatic bile duct adenoma in a patient with chronic hepatitis B accompanied by elevation of alpha-fetoprotein
Jem Ma Ahn, Yong-Han Paik, Jun Hee Lee, Ju Yeon Cho, Won Sohn, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Byung Chul Yoo
Clin Mol Hepatol 2015;21(4):393-397.
Published online December 24, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.4.393

A 51-year-old male patient with chronic hepatitis B was referred to our hospital due to a 1-cm liver nodule on ultrasonography. Alpha-fetoprotein (AFP) was slightly elevated. The nodule showed prolonged enhancement on dynamic liver magnetic resonance imaging and appeared as a hyperintensity on both diffusion-weighted and T2-weighted imaging. The nodule was followed up because it was small and typical findings of hepatocellular carcinoma (HCC) were not observed in the dynamic imaging investigations. However, liver contrast-enhanced ultrasonography performed 1 month later showed enhancement during the arterial phase and definite washout during the delayed phase. Also, AFP had increased to over 200 ng/mL even though AST and ALT were decreased after administering an antiviral agent. He was presumptively diagnosed as HCC and underwent liver segmentectomy. Microscopy findings of the specimen indicated bile duct adenoma. After resection, the follow-up AFP had decreased to within the normal range. This patient represents a case of bile duct adenoma with AFP elevation mimicking HCC on contrast-enhanced ultrasonography.

Citations

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  • Bile duct adenoma: imaging features and radiologic–pathologic correlation
    Ryoji Tatsumi, Shin Ichihara, Hirokazu Suii, Masakatsu Yamaguchi, Tomohiro Arakawa, Tomoaki Nakajima, Yasuaki Kuwata, Itaru Ozeki, Shuhei Hige, Joji Toyota, Yoshiyasu Karino
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Original Articles

The retrospective cohort study for survival rate in patients with advanced hepatocellular carcinoma receiving radiotherapy or palliative care
Hyuk Soo Eun, Min Jung Kim, Hye Jin Kim, Kwang Hun Ko, Hee Seok Moon, Eaum Seok Lee, Seok Hyun Kim, Heon Young Lee, Byung Seok Lee
Korean J Hepatol 2011;17(3):189-198.
Published online September 30, 2011
DOI: https://doi.org/10.3350/kjhep.2011.17.3.189
Background/Aims

This study was conducted to investigate the assessment of treatment efficacy of radiotherapy (RT) and other therapeutic modalities compared with palliative care only for treatment with advanced hepatocellular carcinoma (HCC).

Methods

From 2002 to 2010, based on the case of 47 patients with advanced HCC, we have investigated each patients' Child-Pugh's class, ECOG performance, serum level of alpha fetoprotein and other baseline characteristics that is considered to be predictive variables and values for prognosis of HCC. Out of overall patients, the 29 patients who had received RT were selected for one group and the 18 patients who had received only palliative care were classified for the other. The analysis in survival between the two groups was done to investigate the efficacy of RT.

Results

Under the analysis in survival, the mean survival time of total patients group was revealed between 30.1 months and 45.9 months in RT group, while it was 4.8 months in palliative care group, respectively. In the univariate analysis for overall patients, there were significant factors which affected survival rate like as follows: ECOG performance, Child-Pugh's class, the tumor size, the type of tumor, alpha fetoprotein, transarterial chemoembolization, and RT. The regressive analysis in multivariate Cox for total patients. No treatment under radiotherapy and high level of Child-Pugh's class grade were independent predictors of worse overall survival rate in patients. In contrast, for the subset analysis of the twenty-nine patients treated with radiotherapy, the higher serum level of alpha fetoprotein was an independent predictors of worse overall survival rate in patients.

Conclusions

We found that the survival of patients with advanced HCC was better with radiotherapy than with palliative care. Therefore, radiotherapy could be a good option for in patients with advanced HCC.

Citations

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  • Characteristics and survival of advanced untreated hepatocellular carcinoma of non-viral etiology
    Senarath Pathiranage Nimasha Ekanayaka, Nathasha Luke, Suchintha Bandara Thilakarathne, Anuradha Dassanayake, Mahiman Bhaagya Gunetilleke, Madunil A. Niriella, Rohan Chaminda Siriwardana
    Indian Journal of Gastroenterology.2024; 43(6): 1176.     CrossRef
  • Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma
    Kuan-Wei Huang, Yu-Tsung Lai, Guann-Jen Chern, Shao-Feng Huang, Chia-Lung Tsai, Yun-Chieh Sung, Cheng-Chin Chiang, Pi-Bei Hwang, Ting-Lun Ho, Rui-Lin Huang, Ting-Yun Shiue, Yunching Chen, Sheng-Kai Wang
    Biomacromolecules.2018; 19(6): 2330.     CrossRef
  • Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis
    Jeong Il Yu, Hee Chul Park
    World Journal of Gastroenterology.2016; 22(30): 6851.     CrossRef
  • 2014 Korean Liver Cancer Study Group-National Cancer Center Korea Practice Guideline for the Management of Hepatocellular Carcinoma

    Korean Journal of Radiology.2015; 16(3): 465.     CrossRef
  • Hepatocellular carcinoma: Surgeon's view on latest findings and future perspectives
    Jan Erik Slotta
    World Journal of Hepatology.2015; 7(9): 1168.     CrossRef
  • Considerations for Radiation Therapy in Hepatocellular Carcinoma: The Radiation Oncologists' Perspective
    Jeong Il Yu, Hee Chul Park
    Digestive Diseases.2014; 32(6): 755.     CrossRef
  • 9,571 View
  • 73 Download
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Could patients who underwent hepatic resection due to hepatocellular carcinoma with high alpha-fetoprotein be monitored for recurrence by alpha-fetoprotein Level?
Woo Young Shin, M.D., Kyung-Suk Suh, M.D.1, Taehoon Kim, M.D.1, Young Min Jeon, M.D.1, Nam-Joon Yi, M.D.1, Kuhn Uk Lee, M.D.1
Korean J Hepatol 2010;16(2):168-175.
Published online June 25, 2010
DOI: https://doi.org/10.3350/kjhep.2010.16.2.168
Background/Aims
The follow-up strategy after hepatectomy for hepatocellular carcinoma (HCC) usually depends on the experience of physician, resulting in frequent imaging studies, which leads to increased cost. Hence, we investigated the role of monitoring alpha-fetoprotein (AFP) levels after hepatectomy in patients with preoperative high AFP. Methods: From January 2000 to December 2004, 66 patients who underwent curative hepatectomy due to HCC with preoperative AFP level >400 ng/ml were reviewed. Changes in AFP level after the operation were investigated. The recurrence was suspected in case of two consecutive increase of AFP over cut-off value. Cut-off value was determined by ROC curve. All patients were divided into 2 groups: patients who met the definition (Group S) and those who didn`t (Group D). Results: AFP level of 20ng/ml was proposed as the cut-off value for diagnosis of recurrence by ROC curve. Thirty two patients who didn`t have the AFP level decreased below 20 ng/ml after the resection had HCC recurred, whereas 16 out of 34 patients who had AFP decreased had tumor recurrence. The AFP level of patients without recurrence was kept below 20 ng/ml during the follow-up. The AFP level of 44 out of 48 recurred patients increased over 20ng/ml upon recurrence. By definition, group D were 5 patients. In 4 patients of group D, the AFP level didn`t increase above 20 ng/ml upon recurrence. These patients had HCC and they recurred 1 year after the surgery. Conclusions: In patients with preoperative AFP level >400 ng/ml, the AFP level tended to increase above 20ng/ml at recurrence mostly within 1 year. Hence, we proposed that these patients could be monitored by only AFP until 1 year after surgery.

Citations

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  • Alpha-fetoprotein level to total tumor volume as a predictor of hepatocellular carcinoma recurrence after resection. A retrospective cohort study
    Hazem M. Zakaria, Anwar Mohamed, Hazem Omar, Nahla K. Gaballa
    Annals of Medicine and Surgery.2020; 54: 109.     CrossRef
  • Serum alpha-fetoprotein level per total tumor volume as a predictor of recurrence of hepatocellular carcinoma after resection
    Yeshika Sharma, Michael J. Weaver, Daniel R. Ludwig, Kathryn Fowler, Neeta Vachharajani, William C. Chapman, Jeffrey S. Crippin
    Surgery.2018; 163(5): 1002.     CrossRef
  • Localized Uterine Recurrence of Hepatocellular Carcinoma 4 Years after Curative Resection
    Sang Jin Lee, Jung Woo Shin, Neung Hwa Park, Yang Won Nah, Hang Jo Yoo, Yoong Ki Jung, Hye Jeong Choi
    Korean Journal of Medicine.2012; 82(5): 603.     CrossRef
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Case Report

A case of Liver metastasis of gastric hepatoid adenocarcinoma
Eun Hyoung Jeong, M.D., Dong Hyun Kim, M.D., Sung Ho Ma, M.D., Eui Jong Chung, M.D., Sang Su Bae, M.D., A Young Park, M.D.1, Hyung Jun Chu, M.D.
Korean J Hepatol 2009;15(2):201-208.
Published online June 30, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.2.201
We report herein a case of hepatoid adenocarcinoma of the stomach with liver metastasis. Gastric carcinoma generally presents as adenocarcinoma and rarely shows a hepatoid pattern, which can produce alphafetoprotein (AFP). The stomach is one of the common sites at which hepatoid adenocarcinoma has been detected. A 75-year-old female patient was admitted to the hospital with a symptom of epigastric discomfort. Gastrofibroscopy revealed a large tumor occupying the greater curvature of the stomach body. The level of serum AFP was markedly increased. Abdominal computed tomography revealed multiple liver masses. Biopsy samples of the gastric lesion and liver masses finally confirmed her case as hepatoid adenocarcinoma in the stomach with liver metastasis. The AFP-producing gastric carcinoma needs special attention because it often presents with early liver metastasis and has a poor prognosis. (Korean J Hepatol 2009;15:201-208)

Citations

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  • PRISMA-Compliant Article
    Bao-Ge Qu, Wei-Min Bi, Bao-Teng Qu, Tao Qu, Xing-Hai Han, Hui Wang, Yuan-Xun Liu, Yi-Guo Jia
    Medicine.2016; 95(15): e3399.     CrossRef
  • A Case of Hepatic Metastasis of Gastric Hepatoid Adenocarcinoma Mistaken for Primary Hepatocellular Carcinoma
    Ji Yoon Moon, Gwang Ha Kim, Jae Hoon Cheong, Bong Eun Lee, Dong Yup Ryu, Geun Am Song
    The Korean Journal of Gastroenterology.2012; 60(4): 262.     CrossRef
  • 5,951 View
  • 49 Download
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Original Article

Clinical Features of Hepatocellular Carcinoma with Reference to Serum Alpha-fetoprotein Levels in Korean Patients
Jong Cheol Kim, M.D., Soong Hwan Lee, M.D., Byung Joo Roh, M.D. Sung Woo Kim, M.D., Sung Soo Park, M.D. and Dong Hoo Lee, M.D.*
Korean J Hepatol 1999;5(4):322-331.
Background/Aims
As a tumor marker, alpha-fetoprotein is widely used. Diagnositic cut-off value is known as 400 ng/mL in sera. This study is aimed to determine the clinical features of hepatocellular carcinoma (HCC) with reference to serum AFP levels in Korean patients. Methods: From May 1990 to March 1998, 367 patients diagnosed as HCC, hospitalized and followed-up at Hanyang University Hospital, have been retrospectively analyzed with special reference on serum AFP level at time of diagnosis. The differences in clinical, hematological, and radiological features of HCC, as well as the survival rate in the two groups have been compared. Group 1 (N=182) was defined as an AFP level lower than 400 ng/mL, group 2 (N=185) was defined as an AFP level greater than 400 ng/mL. Comparisons were made by student's t test or chi-square test. Survival rate was calculated from the time of diagnosis by Kaplan-Meier method. Survival curves were also compared using log-rank test. P values less than 0.05 were considered significant. Results: The patients with serum AFP levels above 400 ng/mL showed (1) a lower mean age; (2) a higher level of AST; (3) a higher level of AST/ALT ratio; (4) a high incidence of liver cirrhosis; (5) a high incidence of portal vein thrombosis; (6) a high incidence of positive HBsAg; (7) a low incidence of anti-HCV; (8) a low incidence of small HCC but high incidence of large HCC; (9) a high incidence of more advanced TNM stage; (10) a low incidence of single nodular type and high incidence of diffuse type. Conclusions: Depending on the value of AFP, HCC has some clinical features. In hepatocellular carcinoma, high levels of AFP represent young age, HBV infection more than HCV infection and advanced disease state. (Korean J Hepatol 1999;5:322-331)
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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.
  • 3,396 View
  • 24 Download

Original Article

Optimal Cut-off Value of PIVKA-II for Diagnosis of Hepatocellular Carcinoma - Using ROC Curve -
Myong Jin Kim , Kang Woo Bae , Pyoung Ju Seo , In Kook Jeong , Jung Hyuk Kim , Bo Han Lee , Ki Tae Bang , Dong Woo Kim , Il Han Song
Korean J Hepatol 2006;12(3):404-411.
Background/Aims
Protein induced by vitamin K absence or antagonist-II (PIVKA-II), also known as des-carboxyprothrombin (DCP), can be used as an alternative tool to alpha-fetoprotein (AFP) for surveillance of hepatocellular carcinoma (HCC). The aims of the present study were to compare PIVKA- II levels between the patients with HCC and patients with non-HCC chronic liver disease, to evaluate the correlation of PIVKA-II and AFP in HCC patients, and finally to estimate the optimal cut-off value for PIVKA-II for the diagnosis of HCC with using the receiver operating characteristic (ROC) curve. Methods: A total of 227 consecutive patients with HCC (n=42) or chronic liver disease (n=185) were enrolled in this study. HCC was diagnosed histologically or by imaging such as computed tomography, magnetic resonance imaging or angiography. The serum PIVKA-II and AFP levels were measured by electrochemiluminoimmunoassay with using the Haicatch PIVKA-II kit and by immunoradiometric assay, respectively. Results: The PIVKA-II level in the HCC patients was significantly higher than the non-HCC chronic liver disease patients (903.0±1156.7 vs. 111.7±211.0 mAU/ mL, respectively, P<0.01). PIVKA-II and AFP showed a statistical correlation in HCC patients (r=0.46, P<0.01). The sensitivity and specificity of PIVKA-II for the diagnosis of HCC were 66.7% and 74.1%, respectively, and when tasted together with AFP, the sensitivity was increased by 85.7%. For the ROC curve of PIVKA-II in HCC patients, the specificity of a 250 mAU/mL level of PIVKA-II was 95%. Conclusions: PIVKA-II was as useful surveillance tool for differentiating HCC from chronic liver disease, and a PIVKA-II value of 250 mAU/ mL was proposed as a significant cut-off value for diagnosis of hepatocellular carcinoma.
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Case Report
Liver Metastasis of Colon Cancer with a High Serum alpha-Fetoprotein Level: Report of a Case
Min An, M.D., Jeong A Shin, M.D., Sang-Min Lee, M.D., Tak Yoon, M.D.1, Weon Seo Park, M.D.2, Joon Il Choi, M.D., and Chang-Min Kim, M.D.
Korean J Hepatol 2006;12(4):562-567.
We report herein a case of 72-year-old woman in whom liver metastasis of colon cancer was presented with a marked elevation of serum alpha-fetoprotein (AFP) level. She was transferred to our hospital for multiple liver masses found on ultrasonogram. Abdominal computed tomogram revealed multiple low-density masses in the liver and wall thickening of the hepatic flexure of colon. The serum AFP level was 10,718.8 ng/mL. Colonoscopic findings of ulcerofungating mass suggested liver metastasis from colon cancer. However, the possibility of combined hepatocellular carcinoma could not be ruled out due to serum AFP elevation. Both colon and liver biopsies revealed moderately differentiated tubular adenocarcinoma. Using an immunohistochemical staining, the adenocarcinoma in liver showed focal positive to AFP, but not in colon. This case represents a very rare case of colon cancer with a marked elevation of serum AFP. (Korean J Hepatol 2006;12:562-567)
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