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"Diagnosis"

Correspondences

Correspondence to editorial on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
Soon Sun Kim, Hyung Seok Kim, Jae Youn Cheong, Jung Woo Eun
Clin Mol Hepatol 2026;32(1):e72-e74.
Published online April 4, 2025
DOI: https://doi.org/10.3350/cmh.2025.0350
  • 1,997 View
  • 25 Download

Autoimmune liver disease

Correspondence to editorial on “Prediction of primary biliary cholangitis among health check-up population with anti-mitochondrial M2 antibody positive”
Haolong Li, Song Liu, Xu Wang, Li Wang, Tengda Xu, Yongzhe Li
Clin Mol Hepatol 2025;31(2):e194-e196.
Published online February 24, 2025
DOI: https://doi.org/10.3350/cmh.2025.0181
  • 4,901 View
  • 35 Download

Original Article

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

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to letter to the editor on “GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma”
    Hyung Seok Kim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
    Clinical and Molecular Hepatology.2026; 32(1): e103.     CrossRef
  • The evolving landscape of biomarkers for systemic therapy in advanced hepatocellular carcinoma
    Xinyu Guo, Zhongwei Zhao, Lingyi Zhu, Shuang Liu, Lingling Zhou, Fazong Wu, Shiji Fang, Minjiang Chen, Liyun Zheng, Jiansong Ji
    Biomarker Research.2025;[Epub]     CrossRef
  • Advances in research regarding epithelial-mesenchymal transition and prostate cancer
    Xi Wei, Rui Liu, Wei Li, Qi Yu, Qing Tao Yang, Tao Li
    Frontiers in Cell and Developmental Biology.2025;[Epub]     CrossRef
  • Serum Proteomic Profile Based on the TGF‐β Pathway Stratifies Risk of Hepatocellular Carcinoma
    Xiyan Xiang, Kirti Shetty, Herbert Yu, Bibhuti Mishra, Linda L. Wong, Xianghong Jasmine Zhou, Sanjaya K. Satapathy, James M. Crawford, Patricia S. Latham, Steven‐Huy Han, Brandon Mathew, Nabil N. Dagher, Lawrence Lau, Fellanza Cacaj, Anil K. Vegesna, Srin
    Liver International.2025;[Epub]     CrossRef
  • Systematic analysis of the expression profiles and prognostic values of the FAM72 family in liver cancer
    Weihao Kong, Long Teng, Kangjie Zhang, Yajun Zou, Xingyu Wang, Jianlin Zhang
    Biochemistry and Biophysics Reports.2025; 44: 102358.     CrossRef
  • 13,138 View
  • 991 Download
  • 4 Web of Science
  • Crossref

Reply to Correspondence

Editorial

Hepatic neoplasm

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to editorial on “Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma”
    Yang Liu, Fan Peng, Siyuan Wang, Jinliang Xing
    Clinical and Molecular Hepatology.2025; 31(2): e166.     CrossRef
  • Reply to correspondence on “Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma”
    Hyuk Soo Eun
    Clinical and Molecular Hepatology.2025; 31(2): e215.     CrossRef
  • 5,898 View
  • 53 Download
  • Crossref

Correspondence

Liver fibrosis, cirrhosis, and portal hypertension

Correspondence to editorial on: “Gut microbiome and metabolome signatures in liver cirrhosis-related complications”
Satya Priya Sharma, Ki Tae Suk
Clin Mol Hepatol 2025;31(1):e74-e77.
Published online October 15, 2024
DOI: https://doi.org/10.3350/cmh.2024.0872

Citations

Citations to this article as recorded by  Crossref logo
  • Phocaeicola plebeius oral treatment improve fibrosis by reversing cirrhosis-related hepatic gene dysregulation
    Satya Priya Sharma, Min-Gi Cha, Goo-Hyun Kwon, Seol Hee Song, Jeong Ha Park, Min Ju Kim, Jung A Eom, Kyeong Jin Lee, Sang Jun Yoon, Hyunjoon Park, Sung-Min Won, Ki-Kwang Oh, Young Lim Ham, Gwang Ho Baik, Dong Joon Kim, Ki Tae Suk
    Life Sciences.2025; 381: 123979.     CrossRef
  • 6,138 View
  • 58 Download
  • 1 Web of Science
  • Crossref

Original Article

Hepatic neoplasm

Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang Liu, Fan Peng, Siyuan Wang, Huanmin Jiao, Kaixiang Zhou, Wenjie Guo, Shanshan Guo, Miao Dang, Huanqin Zhang, Weizheng Zhou, Xu Guo, Jinliang Xing
Clin Mol Hepatol 2025;31(1):196-212.
Published online October 15, 2024
DOI: https://doi.org/10.3350/cmh.2024.0527
Background/Aims
Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).
Methods
Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).
Results
The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively).
Conclusions
We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Citations

Citations to this article as recorded by  Crossref logo
  • Integrative metabolomic and transcriptomic profiling reveals distinct metabolic signatures of hepatocellular carcinoma arising from cirrhosis
    Junxi Ni, Qiuming Song, Daoli Liu, Yongwei Zhang, Yun Sun
    Computational Biology and Chemistry.2026; 121: 108863.     CrossRef
  • Transcriptome combined with single-cell sequencing explored prognostic markers associated with T cell exhaustion characteristics in head and neck squamous carcinoma
    Jie Liu, Penghui Li, Yuanyuan Zhang, Lian Zheng
    Scientific Reports.2025;[Epub]     CrossRef
  • Hepatocyte mitochondrial DNA activated store-operated Ca2+ entry via Stim1/Orai1-induced podocyte injury in trichloroethylene sensitized mice: A new insight in liver and kidney crosstalk
    Luo-lun Dong, Xue-qian Jia, Hai-bo Xie, Li-fu Zhu, Peng-cheng Zhou, Rui-xuan Cheng, Chun-lin Cao, Qi-xing Zhu, Jia-xiang Zhang
    Toxicology and Applied Pharmacology.2025; 503: 117465.     CrossRef
  • Mitochondrial metabolism and cancer therapeutic innovation
    Hongxiang Du, Tianhan Xu, Sihui Yu, Sufang Wu, Jiawen Zhang
    Signal Transduction and Targeted Therapy.2025;[Epub]     CrossRef
  • Mitochondrial echoes in the bloodstream: decoding ccf-mtDNA for the early detection and prognosis of hepatocellular carcinoma
    Yu-De Chu, Wei-Ting Chen, Wey-Ran Lin, Ming-Wei Lai, Chau-Ting Yeh
    Cell & Bioscience.2025;[Epub]     CrossRef
  • Circulating Cell‐Free Mitochondrial DNA as a Prognostic Biomarker in Patients With HBV‐Related Acute‐on‐Chronic Liver Failure
    Qiankun Hu, Jiajia Han, Chong Chen, Shuai Tao, Chenlu Huang, Jiacheng Lin, Xun Qi, Zhiping Qian, Mengxin Lu, Xinyan Li, Yi Zhang, Xuhua Jiang, Jianming Zheng, Huazhen Zhao, Feifei Yang, Jiming Zhang, Liang Chen, Xiaoni Kong, Xueyun Zhang, Yuxian Huang
    Journal of Medical Virology.2025;[Epub]     CrossRef
  • Mitochondrial damage-associated molecular patterns (mito-DAMPs): Determinants of hepatopathy progression and therapeutic implications
    Ranyi Luo, Yun Yang, Yinhao Zhang, Xiaoyong Xue, Mengyu Guo, Xiaojiaoyang Li
    Pharmacological Research.2025; 221: 107980.     CrossRef
  • Targeting liver cancer stem cells: the prognostic significance of MRPL17 in immunotherapy response
    Jingjing Shao, Tianye Zhao, Jibin Liu, Peipei Kang
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • 6,995 View
  • 221 Download
  • 11 Web of Science
  • Crossref

Reply to Correspondence

Autoimmune liver disease

  • 5,184 View
  • 48 Download

Correspondence

Autoimmune liver disease

Citations

Citations to this article as recorded by  Crossref logo
  • Reply to correspondence on “Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity”
    Atsumasa Komori
    Clinical and Molecular Hepatology.2024; 30(4): 1035.     CrossRef
  • 6,107 View
  • 51 Download
  • 1 Web of Science
  • Crossref

Original Article

Autoimmune liver disease

Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity
Soomin Ahn, Sook-Hyang Jeong, Eun Ju Cho, Kyoungbun Lee, Gilhyang Kim, Haeryoung Kim
Clin Mol Hepatol 2024;30(1):37-48.
Published online November 13, 2023
DOI: https://doi.org/10.3350/cmh.2023.0325
Background/Aims
The histological criteria in the 1999 and 2008 scoring systems proposed by the International Autoimmune Hepatitis Group (IAIHG) have their inherent limitations in diagnosing autoimmune hepatitis (AIH). In this study, we evaluated the histology components of four scoring systems (1. revised original scoring system [“1999 IAIHG”], 2. simplified scoring system [“2008 IAIHG”], 3. modified histologic criteria [“2017 UCSF”], and 4. a new histologic criteria proposed by the International AIH Pathology Group [“2022 IAHPG”]) in AIH patients.
Methods
Medical records and liver biopsies were retrospectively reviewed for 68 patients from two independent medical institutions, diagnosed with AIH based on the 1999 IAIHG system between 2006 and 2016. The histological features were reviewed in detail, and the four histological scoring systems were compared.
Results
Out of the 68 patients, 56 (82.4%) patients met the “probable” or “definite” AIH criteria of the 2008 IAIHG system, and the proportion of histologic score 2 (maximum) was 40/68 (58.8%). By applying the 2017 UCSF criteria, the number of histology score 2 increased to 60/68 (88.2%), and “probable” or “definite” AIH cases increased to 61/68 (89.7%). Finally, applying the 2022 IAHPG histology score resulted in the highest number of cases with histologic score 2 (64/68; 94.1%) and with a diagnosis of “probable” or “definite” AIH (62/68; 91.2%).
Conclusions
The recently proposed UCSF/IAHPG histological criteria increased the histology score of AIH. Substituting the histology component of the 2008 IAIHG system with the 2022 IAHPG criteria increased the sensitivity for diagnosing AIH (≥“Probable AIH”) from 82.4% to 91.2%.

Citations

Citations to this article as recorded by  Crossref logo
  • Quo vadis autoimmune hepatitis? - Summary of the 5th international autoimmune hepatitis group research workshop 2024
    Bastian Engel, David N. Assis, Mamatha Bhat, Jan Clusmann, Joost PH. Drenth, Alessio Gerussi, María-Carlota Londoño, Ye Htun Oo, Ida Schregel, Marcial Sebode, Richard Taubert
    JHEP Reports.2025; 7(2): 101265.     CrossRef
  • Histopathology of Autoimmune Hepatitis: An Update
    Despoina Myoteri, Stratigoula Sakellariou, Dina G. Tiniakos
    Advances in Anatomic Pathology.2025; 32(6): 414.     CrossRef
  • EASL Clinical Practice Guidelines on the management of autoimmune hepatitis
    George Dalekos, Nikolaos Gatselis, Joost P. Drenth, Michael Heneghan, Marianne Jørgensen, Ansgar W. Lohse, Maria Londoño, Luigi Muratori, Maria Papp, Marianne Samyn, Dina Tiniakos, Ana Lleo
    Journal of Hepatology.2025; 83(2): 453.     CrossRef
  • Evaluation of the histological scoring systems of autoimmune hepatitis: A significant step towards the optimization of clinical diagnosis
    Atsumasa Komori
    Clinical and Molecular Hepatology.2024; 30(2): 157.     CrossRef
  • Reply to: “Evaluation of the histological scoring systems of autoimmune hepatitis: A significant step towards the optimization of clinical diagnosis”
    Haeryoung Kim, Sook-Hyang Jeong
    Clinical and Molecular Hepatology.2024; 30(2): 291.     CrossRef
  • Reply to correspondence on “Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity”
    Atsumasa Komori
    Clinical and Molecular Hepatology.2024; 30(4): 1035.     CrossRef
  • The utility of the mHAI scoring system in pediatric autoimmune hepatitis diagnosis and its association with treatment response
    Wei Chen, Gillian Noel, Mansi Amin, Fengming Chen
    Annals of Diagnostic Pathology.2024; 73: 152381.     CrossRef
  • Diagnosis and Treatment of Patients with Autoimmune Hepatitis (Experts’ Agreement)
    Yu. G. Sandler, E. V. Vinnitskaya, K. L. Raikhelson, K. V. Ivashkin, S. N. Batskikh, E. N. Aleksandrova, D. T. Abdurakhmanov, D. I. Abdulganieva, I. G. Bakulin, A. O. Bueverov, S. L. Vorobyev, O. A. Gerasimova, A. I. Dolgushina, M. S. Zhuravleva, L. Yu. I
    Russian Journal of Gastroenterology, Hepatology, Coloproctology.2024; 34(6): 100.     CrossRef
  • 7,667 View
  • 262 Download
  • 6 Web of Science
  • Crossref

Guideline

Autoimmune liver disease

KASL clinical practice guidelines for management of autoimmune hepatitis 2022
The Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2023;29(3):542-592.
Published online May 3, 2023
DOI: https://doi.org/10.3350/cmh.2023.0087

Citations

Citations to this article as recorded by  Crossref logo
  • Risk of Extrahepatic Malignancies in Patients With Autoimmune Hepatitis: A Nationwide Cohort Study
    Sung Won Chung, Ye-Jee Kim, Jihye Lim, Jonggi Choi, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young-Suk Lim, Han Chu Lee, Sehee Kim, Won-Mook Choi
    American Journal of Gastroenterology.2025; 120(10): 2302.     CrossRef
  • Transient elastography for assessing liver fibrosis in autoimmune liver diseases: Excellent performance but limited details: Editorial on “Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver di
    Kyung-Ah Kim
    Clinical and Molecular Hepatology.2025; 31(1): 275.     CrossRef
  • Hard-to-treat autoimmune hepatitis and primary biliary cholangitis: The dawn of a new era of pharmacological treatment
    Atsumasa Komori, Yuki Kugiyama
    Clinical and Molecular Hepatology.2025; 31(1): 90.     CrossRef
  • Comment on “Characteristics and Outcomes of Hepatocellular Carcinoma in Patients with Autoimmune Hepatitis”
    Bilal Ahmad, Ayesha Arshad, Niqab Muhammad
    Digestive Diseases and Sciences.2025; 70(11): 3977.     CrossRef
  • Autoimmune hepatitis. Clinical case
    Anna Usachova, Lyudmila Onyshchuk
    The Ukrainian Scientific Medical Youth Journal.2025; 154(2): 35.     CrossRef
  • Impact of metabolic dysfunction-associated steatotic liver disease on hepatocellular carcinoma risk in autoimmune hepatitis
    Jihye Lim, Ye-Jee Kim, Sehee Kim, Ju Hyun Shim, Ashraf Elbahrawy
    PLOS One.2025; 20(7): e0325066.     CrossRef
  • Incidence and risk factors of hepatocellular carcinoma in patients with autoimmune hepatitis in Asia
    Jiwon Yang, Sun Young Yim, Kunhee Kim, Hye Won Lee, Jonggi Choi
    JHEP Reports.2025; 7(10): 101524.     CrossRef
  • Difficult to treat and refractory autoimmune hepatitis: Recent advances in pharmacological management
    Sayan Malakar, Umair Shamsul Hoda, Suprabhat Giri, Arghya Samanta, Akash Roy, Rajat Gupta, S Rakesh Kumar, Mayank Agarwal, Anubhav Pawar, Sumit Rungta, Uday C Ghoshal
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Mechanistic optimization of inavolisib combined with CDK4/6 inhibitors in the treatment of PIK3CA-mutated breast tumors
    Rongyu Zhu, Haixin Zhang, Fuli Zhang
    Frontiers in Immunology.2025;[Epub]     CrossRef
  • Autoimmune liver diseases in the Asia Pacific region: proceedings of the autoimmune liver disease course at APASL 2025
    Atsushi Tanaka, Sombat Treeprasertsuk, Ming-Ling Chang, Soek-Siam Tan, Cumali Efe, Sook-Hyang Jeong, Xiong Ma, Martin Weltman, Hiroyuki Isayama, Jidong Jia
    Hepatology International.2025;[Epub]     CrossRef
  • Evaluation of the histological scoring systems of autoimmune hepatitis: A significant step towards the optimization of clinical diagnosis
    Atsumasa Komori
    Clinical and Molecular Hepatology.2024; 30(2): 157.     CrossRef
  • Epidemiology of autoimmune liver disease in Korea: evidence from a nationwide real-world database
    Jihye Lim, Hwa Jung Kim
    Orphanet Journal of Rare Diseases.2024;[Epub]     CrossRef
  • The Impact of Histologic Portal T-Cell Density on the Clinical Outcomes in Hepatic Graft-versus-Host Disease and Autoimmune Liver Diseases
    Soon Kyu Lee, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Seok Lee, Younghoon Kim, Ji Won Han, Hyun Yang, Si Hyun Bae, Jeong Won Jang, Jong Young Choi, Seung Ke
    Diagnostics.2024; 14(16): 1745.     CrossRef
  • Diagnostic accuracy of vibration-controlled transient elastography for staging liver fibrosis in autoimmune liver diseases: A systematic review and meta-analysis
    Jihyun An, Young Eun Chon, Gunho Kim, Mi Na Kim, Hee Yeon Kim, Han Ah Lee, Jung Hwan Yu, Miyoung Choi, Dae Won Jun, Seung Up Kim, Ji Won Han, Young-Joo Jin
    Clinical and Molecular Hepatology.2024; 30(Suppl): S134.     CrossRef
  • Analysis of Azathioprine Metabolites in Autoimmune Hepatitis Patient Blood—Method Development and Validation
    Andrea Guba, Patrícia Kováts, Zoltán A. Mezei, Mária Papp, Éva Csősz, Gergő Kalló
    International Journal of Molecular Sciences.2024; 25(20): 11233.     CrossRef
  • AUTOIMMUNE HEPATITIS AND THE COMPLEXITY OF ITS MANAGEMENT: A CLINICAL CASE
    V. N. Zhdan, O. A. Kyrian, M. Yu. Babanina, I. V. Ivanytskyi, M. V. Tkachenko, V. G. Lebid
    Bulletin of Problems Biology and Medicine.2023; 1(2): 179.     CrossRef
  • Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity
    Soomin Ahn, Sook-Hyang Jeong, Eun Ju Cho, Kyoungbun Lee, Gilhyang Kim, Haeryoung Kim
    Clinical and Molecular Hepatology.2023; 30(1): 37.     CrossRef
  • 16,370 View
  • 433 Download
  • 14 Web of Science
  • Crossref

Editorial

Hepatic neoplasm

Citations

Citations to this article as recorded by  Crossref logo
  • Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma
    Ye Rim Kim, Sung Won Chung, Min-Ju Kim, Won-Mook Choi, Jonggi Choi, Danbi Lee, Han Chu Lee, Ju Hyun Shim
    Journal of Hepatocellular Carcinoma.2024; Volume 11: 1235.     CrossRef
  • 6,538 View
  • 66 Download
  • 1 Web of Science
  • Crossref

Reviews

Hepatic neoplasm

Clinical practice guideline and real-life practice in hepatocellular carcinoma: A Korean perspective
Myung Ji Goh, Dong Hyun Sinn, Jong Man Kim, Min Woo Lee, Dong Ho Hyun, Jeong Il Yu, Jung Yong Hong, Moon Seok Choi
Clin Mol Hepatol 2023;29(2):197-205.
Published online January 5, 2023
DOI: https://doi.org/10.3350/cmh.2022.0404
Hepatocellular carcinoma (HCC) is a major cause of death in many countries, including South Korea. To provide useful and sensible advice for clinical management of patients with HCC, the Korean Liver Cancer Association and National Cancer Center Korea Practice Guideline Revision Committee have recently revised the practice guidelines for HCC management. However, there are some differences between practice guidelines and real-life clinical practice. In this review, we describe some key recommendations of the 2022 version of practice guidelines and the real-life clinical situation in South Korea, together with discussion about efforts needed to reduce the difference between guidelines and real-life clinical practice.

Citations

Citations to this article as recorded by  Crossref logo
  • Neutrophil count predicts the complete response after transarterial chemoembolization related to favorable outcome in hepatocellular carcinoma
    Young Mi Hong
    European Journal of Gastroenterology & Hepatology.2025; 37(1): 94.     CrossRef
  • Epidemiological characteristics and precise prophylaxis and control of HBV-associated primary liver cancer
    Yuqi Feng, Letian Fang, Guangwen Cao
    Hepatoma Research.2025;[Epub]     CrossRef
  • A Prospective, Multicenter, Randomized, Noninferiority Trial of Stopad® Versus Tachosil® for Hemostasis After Liver Resection
    Seung Yeon Lim, Gi Hong Choi, Jin Hong Lim, Ho-Seong Han, Yoo-Seok Yoon, Hae Won Lee, Boram Lee, Yeshong Park, MeeYoung Kang, Jinju Kim, Hyelim Joo, Jai Young Cho
    Cancers.2025; 17(5): 757.     CrossRef
  • Reply: Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of hepatocellular carcinoma
    Deok Hwa Seo, Pil Soo Sung
    Hepatology.2025; 81(4): E123.     CrossRef
  • The Association Between Hepatocellular Carcinoma and Gastrointestinal Adenocarcinoma: Is This a New Syndrome in Patients With Cirrhosis? A Case Series
    Fabrizio Bronte, Fabio D'Amato, Maria Rosa Barcellona, Giuseppe Bronte, Giuseppe Malizia, Salvatore Ialuna, Giorgio Fusco, Francesco Verderame, Enrico Bronte, Maria Grazia Bavetta
    Cancer Reports.2025;[Epub]     CrossRef
  • Roadmap for HCC Surveillance and Management in the Asia Pacific
    Masatoshi Kudo, Bui Thi Oanh, Chien-Jen Chen, Do Thi Ngat, Jacob George, Do Young Kim, Luckxawan Pimsawadi, Pisit Tangkijvanich, Raoh-Fang Pwu, Rosmawati Mohamed, Sakarn Bunnag, Sheng-Nan Lu, Sirintip Kudtiyakarn, Tatsuya Kanto, Teerha Piratvisuth, Chao-C
    Cancers.2025; 17(12): 1928.     CrossRef
  • TCR-based cellular immunotherapy for hepatocellular carcinoma: advances, challenges, and prospects
    Wanting Zeng, Wei Zhu, Guosheng Yuan, Jinzhang Chen, Zhanhui Wang, Jinlin Hou, De-Ke Jiang
    Cancer Immunology, Immunotherapy.2025;[Epub]     CrossRef
  • Development and validation of a risk prediction model for patients with hepatocellular carcinoma receiving atezolizumab–bevacizumab
    Heechul Nam, Dong Yun Kim, Do Young Kim, Ji Hoon Kim, Chang Wook Kim, Jaejun Lee, Keungmo Yang, Ji Won Han, Pil Soo Sung, Seung Kew Yoon, Hee Sun Cho, Hyun Yang, Si Hyun Bae, Soon Kyu Lee, Jung Hyun Kwon, Soon Woo Nam, Ahlim Lee, Do Seon Song, U Im Chang,
    Hepatology.2025;[Epub]     CrossRef
  • Subset of Child-Pugh Score 7 Shows Comparable Survival Outcomes to Child-Pugh Score 6 in Patients with Hepatocellular Carcinoma Treated with Atezolizumab and Bevacizumab
    Jaejun Lee, Keungmo Yang, Ji Won Han, Pil Soo Sung, Jeong Won Jang, Seung Kew Yoon, Hee Sun Cho, Hyun Yang, Si Hyun Bae, Ji Hoon Kim, Heechul Nam, Chang Wook Kim, Hae Lim Lee, Hee Yeon Kim, Sung Won Lee, Ahlim Lee, Do Seon Song, Myeong Jun Song, Soon Woo
    Clinical Cancer Research.2025; 31(20): 4323.     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
  • The Position of Multikinase Inhibitors in the Era of Immune-Checkpoint Inhibitors for Hepatocellular Carcinoma
    Beom Kyung Kim
    Gut and Liver.2024; 18(1): 3.     CrossRef
  • Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma
    Josep M. Llovet, Roser Pinyol, Mark Yarchoan, Amit G. Singal, Thomas U. Marron, Myron Schwartz, Eli Pikarsky, Masatoshi Kudo, Richard S. Finn
    Nature Reviews Clinical Oncology.2024; 21(4): 294.     CrossRef
  • High‐dose proton pump inhibitor treatment is associated with a higher mortality in cirrhotic patients: A multicentre study
    Jun Sik Yoon, Ji Hoon Hong, Soo Young Park, Seung Up Kim, Hwi Young Kim, Ju Yeon Kim, Moon Haeng Hur, Min Kyung Park, Yun Bin Lee, Han Ah Lee, Gi‐Ae Kim, Dong Hyun Sinn, Sung Jae Park, Youn Jae Lee, Yoon Jun Kim, Jung‐Hwan Yoon, Jeong‐Hoon Lee
    Alimentary Pharmacology & Therapeutics.2024; 59(8): 973.     CrossRef
  • Role of reimbursement and Physicians' awareness in the survival of sorafenib‐eligible advanced hepatocellular carcinoma patients
    Hui‐Ling Huang, Te‐Sheng Chang, Lariza Marie Canseco, Fan Wu, Sheng‐Nan Lu
    The Kaohsiung Journal of Medical Sciences.2024; 40(6): 589.     CrossRef
  • Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma
    Ye Rim Kim, Sung Won Chung, Min-Ju Kim, Won-Mook Choi, Jonggi Choi, Danbi Lee, Han Chu Lee, Ju Hyun Shim
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Hepatic neoplasm

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Chinese perspective
Diyang Xie, Jieyi Shi, Jian Zhou, Jia Fan, Qiang Gao
Clin Mol Hepatol 2023;29(2):206-216.
Published online December 22, 2022
DOI: https://doi.org/10.3350/cmh.2022.0402
Liver cancer is the fourth most prevalent and the second most lethal cancer in China. Hepatitis B virus (HBV) infection represents a major risk factor for hepatocellular carcinoma (HCC). Liver ultrasonography plus alpha-fetoprotein every 6 months continues to be the predominant surveillance modality. The age-Male-ALBI-Platelets score was recommended in the recent 2022 Chinese guidelines to predict HCC occurrence. The Chinese liver cancer (CNLC) staging system proposed in the 2017 guidelines continues to be the standard model for staging with modifications in the treatment allocations. Considering the aggressive nature of HBV-associated HCC, multimodal and high-intensity strategies like the addition of immunotherapy-based systemic treatment to local therapies, including resection, ablation, and intra-arterial therapies, have been adopted in real-life practices in China. The latest Chinese guidelines recommend atezolizumab plus bevacizumab, suntilimab plus a bevacizumab analog, lenvatinib, sorafenib, donafenib, and FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy as first-line treatment without priority. Regorafenib, apatinib, camrelizumab, and tislelizumab have been added as second-line systemic therapies for patients who progressed on sorafenib. Systemic therapies adopted in real-life practice are sophisticated with various combination modalities and different sequences.

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Steatotic liver disease

Surveillance of the progression and assessment of treatment endpoints for nonalcoholic steatohepatitis
Yi-wen Shi, Jian-Gao Fan
Clin Mol Hepatol 2023;29(Suppl):S228-S243.
Published online December 14, 2022
DOI: https://doi.org/10.3350/cmh.2022.0401
Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease (NAFLD) characterized by steatosis-associated inflammation and liver injury. Without effective treatment or management, NASH can have life-threatening outcomes. Evaluation and identification of NASH patients at risk for adverse outcomes are therefore important. Key issues in screening NASH patients are the assessment of advanced fibrosis, differentiation of NASH from simple steatosis, and monitoring of dynamic changes during follow-up and treatment. Currently, NASH staging and evaluation of the effectiveness for drugs still rely on pathological diagnosis, despite sample error issues and the subjectivity associated with liver biopsy. Optimizing the pathological assessment of liver biopsy samples and developing noninvasive surrogate methods for accessible, accurate, and safe evaluation are therefore critical. Although noninvasive methods including elastography, serum soluble biomarkers, and combined models have been implemented in the last decade, noninvasive diagnostic measurements are not widely applied in clinical practice. More work remains to be done in establishing cost-effective strategies both for screening for at-risk NASH patients and identifying changes in disease severity. In this review, we summarize the current state of noninvasive methods for detecting steatosis, steatohepatitis, and fibrosis in patients with NASH, and discuss noninvasive assessments for screening at-risk patients with a focus on the characteristics that should be monitored at follow-up.

Citations

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Steatotic liver disease

Non-alcoholic fatty liver disease: the pathologist’s perspective
Wei-Qiang Leow, Anthony Wing-Hung Chan, Paulo Giovanni L. Mendoza, Regina Lo, Kihan Yap, Haeryoung Kim
Clin Mol Hepatol 2023;29(Suppl):S302-S318.
Published online November 15, 2022
DOI: https://doi.org/10.3350/cmh.2022.0329
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases characterized by fatty accumulation in hepatocytes, ranging from steatosis, non-alcoholic steatohepatitis, to cirrhosis. While histopathological evaluation of liver biopsies plays a central role in the diagnosis of NAFLD, limitations such as the problem of interobserver variability still exist and active research is underway to improve the diagnostic utility of liver biopsies. In this article, we provide a comprehensive overview of the histopathological features of NAFLD, the current grading and staging systems, and discuss the present and future roles of liver biopsies in the diagnosis and prognostication of NAFLD.

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Guideline

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma
Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
Clin Mol Hepatol 2022;28(4):583-705.
Published online October 1, 2022
DOI: https://doi.org/10.3350/cmh.2022.0294
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.

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Review

Imaging diagnosis of hepatocellular carcinoma: Future directions with special emphasis on hepatobiliary magnetic resonance imaging and contrast-enhanced ultrasound
Junghoan Park, Jeong Min Lee, Tae-Hyung Kim, Jeong Hee Yoon
Clin Mol Hepatol 2022;28(3):362-379.
Published online December 27, 2021
DOI: https://doi.org/10.3350/cmh.2021.0361
Hepatocellular carcinoma (HCC) is a unique cancer entity that can be noninvasively diagnosed using imaging modalities without pathologic confirmation. In 2018, several major guidelines for HCC were updated to include hepatobiliary contrast agent magnetic resonance imaging (HBA-MRI) and contrast-enhanced ultrasound (CEUS) as major imaging modalities for HCC diagnosis. HBA-MRI enables the achievement of high sensitivity in HCC detection using the hepatobiliary phase (HBP). CEUS is another imaging modality with real-time imaging capability, and it is reported to be useful as a second-line modality to increase sensitivity without losing specificity for HCC diagnosis. However, until now, there is an unsolved discrepancy among guidelines on whether to accept “HBP hypointensity” as a definite diagnostic criterion for HCC or include CEUS in the diagnostic algorithm for HCC diagnosis. Furthermore, there is variability in terminology and inconsistencies in the definition of imaging findings among guidelines; therefore, there is an unmet need for the development of a standardized lexicon. In this article, we review the performance and limitations of HBA-MRI and CEUS after guideline updates in 2018 and briefly introduce some future aspects of imaging-based HCC diagnosis.

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Guideline

Steatotic liver disease

KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease
Seong Hee Kang, Hye Won Lee, Jeong-Ju Yoo, Yuri Cho, Seung Up Kim, Tae Hee Lee, Byoung Kuk Jang, Sang Gyune Kim, Sang Bong Ahn, Haeryoung Kim, Dae Won Jun, Joon-Il Choi, Do Seon Song, Won Kim, Soung Won Jeong, Moon Young Kim, Hong Koh, Sujin Jeong, Jin-Woo Lee, Yong Kyun Cho, on behalf of The Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2021;27(3):363-401.
Published online June 22, 2021
DOI: https://doi.org/10.3350/cmh.2021.0178

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Original Article

Artificial intelligence, epidemiology, methodology, or others

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome
Han Ah Lee, Jihwan Lim, Hyung Joon Joo, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Do-Sun Lim, Kwan Soo Byun, Yeon Seok Seo
Clin Mol Hepatol 2021;27(3):463-473.
Published online February 15, 2021
DOI: https://doi.org/10.3350/cmh.2020.0351
Background/Aims
Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome.
Methods
Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline.
Results
A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P<0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P<0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level <4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P<0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P<0.05).
Conclusions
Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.

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Review

Autoimmune liver disease

Recent updates on the management of autoimmune hepatitis
Atsumasa Komori
Clin Mol Hepatol 2021;27(1):58-69.
Published online December 10, 2020
DOI: https://doi.org/10.3350/cmh.2020.0189
Autoimmune hepatitis (AIH) is an immunoinflammatory chronic liver disease with dynamic and rather heterogeneous disease manifestations. A trend of increasing prevalence of AIH has been observed worldwide, along with a relative increase in the percentage of male patients. AIH is characterized and diagnosed based on serum biochemistry and liver histology: elevated aminotransferases and serum immunoglobulin G (IgG), the presence of serum anti-nuclear antibody or anti-smooth muscle antibody, and interface lympho-plasmacytic hepatitis. Clinical manifestations differ among disease subtypes with distinct time-frames, i.e., AIH with a chronic insidious onset, and acute-onset AIH (the diagnosis of which is often challenging due to the lack of typical serum findings). The absence of disease-specific biomarkers or histological findings may expand the disease phenotype into drug-induced AIH-like liver injury. Corticosteroids and azathioprine are recommended first-line treatments for AIH. The complete normalization of aminotransferases and serum IgG is an essential treatment response to ensure long-term overall survival. An incomplete response or intolerance to these drugs is considered an indication for second-line treatment, especially with mycophenolate mofetil. Life-long maintenance treatment is required for the majority of patients, but the few who achieve prolonged and stringent biochemical remission with lower alanine aminotransferase and IgG within the normal range may be able to discontinue the medications. In the future, the quality of life of AIH patients should be managed by personalized medicine, including the appropriate selection and dosing of first-line therapy and perhaps alternating with potential therapeutics, and the prediction of the success of treatment withdrawal.

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Original Article

Hepatic neoplasm

Comparison of LI-RADS 2018 and KLCA-NCC 2018 for noninvasive diagnosis of hepatocellular carcinoma using magnetic resonance imaging
Sunyoung Lee, Seung-seob Kim, Dong ryul Chang, Hyerim Kim, Myeong-Jin Kim
Clin Mol Hepatol 2020;26(3):340-351.
Published online June 4, 2020
DOI: https://doi.org/10.3350/cmh.2020.0004
Background/Aims
This study aimed to compare the diagnostic performances of Liver Imaging Reporting and Data System (LI-RADS) 2018 and Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) 2018 criteria on magnetic resonance imaging (MRI) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.
Methods
This retrospective study included 273 treatment-naïve patients (71 patients with extracellular contrast agent [ECA]-MRI and 202 patients with hepatobiliary agent [HBA]-MRI; 352 lesions including 263 HCCs) with high risk of HCC who underwent contrast-enhanced MRI between 2016 and 2017. Two readers evaluated all lesions according to the criteria of LI-RADS 2018 and KLCA-NCC 2018. The per-lesion diagnostic performances were compared using the generalized estimating equation method.
Results
On ECA-MRI, the sensitivity and specificity of LI-RADS 2018 and KLCA-NCC 2018 were not significantly different (LR-5 vs. definite HCC: 75.8% vs. 69.4%, P=0.095 and 95.8% vs. 95.8%, P>0.999; LR-5/4 vs. definite/probable HCC: 87.1% vs.83.9%, P=0.313 and 87.5% vs. 91.7%, P=0.307). On HBA-MRI, definite HCC of KLCA-NCC 2018 showed significantly higher sensitivity (79.1% vs. 68.2%, P<0.001) than LR-5 of LI-RADS 2018 without a significant difference in specificity (93.9% vs. 95.4%, P=0.314). Definite/probable HCC of KLCA-NCC 2018 had higher specificity (92.3% vs. 80.0%, P=0.003) than LR-5/4 of LI-RADS 2018. The sensitivity was lower for definite/probable HCC than for LR-5/4 without statistical significance (85.6% vs. 88.1%, P=0.057).
Conclusions
On ECA-MRI, LI-RADS 2018 and KLCA-NCC 2018 showed comparable diagnostic performances. On HBA-MRI, definite HCC of KLCA-NCC 2018 provided better sensitivity than LR-5 category of LI-RADS 2018 without compromising the specificity, while definite/probable HCC of KLCA-NCC 2018 revealed higher specificity than LR-5/4 of LI-RADS 2018 for diagnosing HCC.

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Reviews

Hepatic neoplasm

Detect or not to detect very early stage hepatocellular carcinoma? The western perspective
Ju Dong Yang
Clin Mol Hepatol 2019;25(4):335-343.
Published online March 29, 2019
DOI: https://doi.org/10.3350/cmh.2019.0010
Very early stage hepatocellular carcinoma (HCC) is defined as a single tumor with the largest diameter of the lesion measuring 2 cm or less according to Barcelona Liver Cancer staging system. Detection of very early stage HCC is clinically important as it confers an excellent prognosis with the 5-year survival rates over 60 to 80% after patients receive curative treatments. While diagnosing HCC at a very early stage is crucial, it is technically challenging and may come with the physical or psychosocial harms related to diagnostic tests. It is further complicated by the fact that patients with very early stage HCC are not prioritized for liver transplant (LT) in the United States organ allocation system. When LT-eligible patients present with an indeterminate lesion measuring between 1 and 2 cm on the multiphasic computed tomography or magnetic resonance imaging, clinicians often observe patients carefully until the lesion grows up to 2 cm so that patients can be eligible to receive a Model for End-Stage Liver Disease (MELD) exception score for HCC in the United States. The European guideline recommends a routine biopsy of such lesion. In conclusion, attempting to detect very early stage HCC is difficult to achieve and controversial. Clinicians should take into account of the risk and the benefit of diagnostic tests, LT candidacy of patients and the local organ allocation system.

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Hepatic neoplasm

Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma: 2018 update
Tae-Hyung Kim, So Yeon Kim, An Tang, Jeong Min Lee
Clin Mol Hepatol 2019;25(3):245-263.
Published online February 14, 2019
DOI: https://doi.org/10.3350/cmh.2018.0090
The goal of this review is to present the similarities and differences among the latest guidelines for noninvasive diagnosis of hepatocellular carcinoma (HCC) of American Association for the Study of Liver Disease (AASLD), European Association for the Study of the Liver (EASL), Liver Imaging Reporting and Data System (LI-RADS), Asian Pacific Association for the Study of the Liver (APASL), and Korean Liver Cancer Association- National Cancer Center (KLCA-NCC) of Korea. In 2018, major guideline updates have been proposed by the AASLD, EASL and KLCA-NCC; AASLD newly incorporated LI-RADS into their HCC diagnostic algorithm. The AASLD and EASL guidelines now include magnetic resonance imaging (MRI) using hepatobiliary contrast media as a first-line diagnostic test in addition to dynamic computed tomography and MRI using extracellular contrast media and the KLCA-NCC and EASL guidelines also include contrast-enhanced ultrasound as a second-line diagnostic test. We will comprehensively review the HCC surveillance and diagnostic algorithms and compare and highlight key features for each guideline. We also address limitations of current systems for the noninvasive diagnosis of HCC.

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Hepatic neoplasm

Gadoxetic acid-enhanced magnetic resonance imaging: Hepatocellular carcinoma and mimickers
Yeun-Yoon Kim, Mi-Suk Park, Khalid Suliman Aljoqiman, Jin-Young Choi, Myeong-Jin Kim
Clin Mol Hepatol 2019;25(3):223-233.
Published online January 21, 2019
DOI: https://doi.org/10.3350/cmh.2018.0107
Gadoxetic acid, a hepatocyte-specific magnetic resonance imaging (MRI) contrast agent, has emerged as an important tool for hepatocellular carcinoma (HCC) diagnosis. Gadoxetic acid-enhanced MRI is useful for the evaluation of earlystage HCC, diagnosis of HCC precursor lesions, and highly sensitive diagnosis of HCC. Furthermore, functional information provided by gadoxetic acid-enhanced MRI can aid in the characterization of focal liver lesions. For example, whereas lesions lack functioning hepatocytes appear hypointense in the hepatobiliary phase, preserved or enhanced expression of organic anion transporting polypeptides in some HCCs as well as focal nodular hyperplasia lead to hyperintensity in the hepatobiliary phase; and a targetoid appearance on transitional phase or hepatobiliary phase imaging can be helpful for identifying the histopathological composition of tumors. While gadoxetic acid-enhanced MRI may improve the sensitivity of HCC diagnosis and provide new insights into the characterization of focal liver lesions, there are many challenges associated with its use. This article reviews the pros and cons of HCC diagnosis with gadoxetic acid-enhanced MRI and discuss some clues in the radiological differentiation of HCC from HCC mimickers.

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Hepatic neoplasm

Contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) 2017 – a review of important differences compared to the CT/MRI system
Tae Kyoung Kim, Seung Yeon Noh, Stephanie R Wilson, Yuko Kono, Fabio Piscaglia, Hyun-Jung Jang, Andrej Lyshchik, Christoph F. Dietrich, Juergen K. Willmann, Alexander Vezeridis, Claude B Sirlin
Clin Mol Hepatol 2017;23(4):280-289.
Published online September 15, 2017
DOI: https://doi.org/10.3350/cmh.2017.0037
Medical imaging plays an important role in the diagnosis and management of hepatocellular carcinoma (HCC). The Liver Imaging Reporting and Data System (LI-RADS) was initially created to standardize the reporting and data collection of CT and MR imaging for patients at risk for HCC. As contrast-enhanced ultrasound (CEUS) has been widely used in clinical practice, it has recently been added to the LI-RADS. While CEUS LI-RADS shares fundamental concepts with CT/MRI LI-RADS, there are key differences between the modalities reflecting dissimilarities in the underlying methods of image acquisition and types of contrast material. This review introduces a recent update of CEUS LI-RADS and explains the key differences from CT/MRI LI-RADS.

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Steatotic liver disease

Non-alcoholic fatty liver diseases: update on the challenge of diagnosis and treatment
Hyunwoo Oh, Dae Won Jun, Waqar K Saeed, Mindie H Nguyen
Clin Mol Hepatol 2016;22(3):327-335.
Published online September 25, 2016
DOI: https://doi.org/10.3350/cmh.2016.0049
The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a “hot potato” for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed. Liver biopsy is the best method rather than a perfect one. Recently, multi-parametric magnetic resonance imagery can estimate the amount of intrahepatic fat successfully and is widely used in clinical trials. But no diagnostic method can discriminate between steatohepatitis and simple steatosis. The other unresolved issue in regard to NAFLD is the absence of satisfactory treatment options. Vitamin E and obeticholic acid have shown protective effects in randomized controlled trials, but this drug has not been approved for use in Korea. This study will provide a description of diagnostic methods and treatments that are currently recommended for NAFLD.

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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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Liver Imaging

Hepatic neoplasm

Liver imaging reporting and data system (LI-RADS) version 2014: understanding and application of the diagnostic algorithm
Chansik An, Gulbahor Rakhmonova, Jin-Young Choi, Myeong-Jin Kim
Clin Mol Hepatol 2016;22(2):296-307.
Published online June 15, 2016
DOI: https://doi.org/10.3350/cmh.2016.0028
Liver Imaging Reporting and Data System (LI-RADS) is a system for interpreting and reporting of computed tomography and magnetic resonance imaging of the liver in patients at risk for hepatocellular carcinoma (HCC). LI-RADS has been developed to address the limitations of prior imaging-based criteria including the lack of established consensus regarding the exact definitions of imaging features, binary categorization (either definite or not definite HCC), and failure to consider non-HCC malignancies. One of the most important goals of LI-RADS is to facilitate clear communication between all the personnel involved in the diagnosis and treatment of HCC, such as radiologists, hepatologists, surgeons, and pathologists. Therefore, clinicians should also be familiar with LI-RADS. This article reviews the LI-RADS diagnostic algorithm, and the definitions and management implications of LI-RADS categories.

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Review

Benign liver tumors and cystic disease of liver

Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma
Massimo Roncalli, Amedeo Sciarra, Luca Di Tommaso
Clin Mol Hepatol 2016;22(2):199-211.
Published online May 18, 2016
DOI: https://doi.org/10.3350/cmh.2016.0101
Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed.

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Case Reports

Hepatic neoplasm

Imaging findings for intravascular large B-cell lymphoma of the liver
Jungmin Bae, Hyo Keun Lim, Ha Young Park
Clin Mol Hepatol 2015;21(3):295-299.
Published online September 30, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.3.295

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma that most commonly involves the central nervous system and skin. To our knowledge, no state-of-the art imaging findings have been reported for hepatic IVLBCL in the English literature. We report the first case of hepatic involvement of IVLBCL along with a literature review.

Citations

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    Seigi Oshima, Soichiro Sakamoto, Ken Takahashi, Toshiyuki Kitano
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    Yingying Han, Qingjiao Li, Dan Wang, Lushan Peng, Tao Huang, Chunlin Ou, Keda Yang, Junpu Wang
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Benign liver tumors and cystic disease of liver

A case of primary hepatic actinomycosis: an enigmatic inflammatory lesion of the liver
Yeon Jung Ha, Ji Hyun An, Ju Hyun Shim, Eun Sil Yu, Jong Jae Kim, Tae Yong Ha, Han Chu Lee
Clin Mol Hepatol 2015;21(1):80-84.
Published online March 25, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.1.80

Primary hepatic actinomycosis is one of the chronic abscess-forming infections of the liver. Accurate diagnosis is frequently delayed due to its indolent course and nonspecific clinical and radiological manifestations. We report a case of a 57-year-old man presenting with asymptomatic multiple hepatic masses on follow-up abdominal computed tomography performed 1 year after stomach cancer surgery. Although a percutaneous liver biopsy procedure was conducted twice in order to obtain confirmative pathology, only a nonspecific organizing abscess with plasma cell infiltration was revealed, without identification of any organism in the tissue cultures. Ultimately, actinomycosis was diagnosed following the detection of sulfur granules on open surgical biopsied tissue. This case suggests that primary hepatic actinomycosis should be considered as one of the possible causes for enigmatic inflammatory lesions of the liver.

Citations

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  • Hepatic actinomycosis: A diagnostic challenge
    Prithiviraj Nabi, Muthukumarassamy Rajakannu, Mukul Vij, Mohamed Rela
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Original Articles

Viral hepatitis

Predicting factors of present hepatitis C virus infection among patients positive for the hepatitis C virus antibody
Chi Hoon Lee, Hyun Phil Shin, Joung Il Lee, Kwang Ro Joo, Jae Myung Cha, Jung Won Jeon, Jun Uk Lim, Joon Ki Min, Dong Hee Kim, Sung Wook Kang, Hyun Jun Joung
Clin Mol Hepatol 2013;19(4):376-381.
Published online December 28, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.4.376
Background/Aims

To identify the predicting factors of present hepatitis C virus (HCV) infection among patients with positivity for antibodies to HCV (anti-HCV).

Methods

We analyzed patients who showed positive enzyme immunoassay (EIA) results and performed an HCV RNA test as a confirmatory test at Kyung Hee University Hospital at Gangdong from June 2006 to July 2012. The features distinguishing the groups with positive and negative HCV RNA results were reviewed.

Results

In total, 490 patients were included. The results of the HCV RNA test were positive and negative in 228 and 262 patients, respectively. The index value of anti-HCV, mean age, platelet counts, total bilirubin, prothrombin time international normalized ratio, albumin and alanine transaminase (ALT) levels differed significantly between the two groups. On multivariable analysis, an index value of anti-HCV >10 [odds ratio (OR)=397.27, P<0.001), ALT >40 IU/L (OR=3.64, P=0.001), and albumin <3.8 g/dL (OR=2.66, P=0.014) were related to present HCV infection.

Conclusions

Although EIA is not a quantitative test, considering the anti-HCV titer with ALT and albumin levels may be helpful in predicting present of HCV infection.

Citations

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    Tayibe Bal, Emre Dirican
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    Jin Gu Kang, Myoung Kuk Jang, Jung Hee Kim, Jang Han Jung, Ji Won Park, Sung Eun Kim, Sang Hoon Park, Myung Seok Lee, Ki Tae Suk, Dong Joon Kim, Hyoung Su Kim
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Artificial intelligence, epidemiology, methodology, or others

Type and cause of liver disease in Korea: single-center experience, 2005-2010
Sang Soo Lee, Young-Sang Byoun, Sook-Hyang Jeong, Yeo Myung Kim, Ho Gil, Bo-Young Min, Mun Hyuk Seong, Eun Sun Jang, Jin-Wook Kim
Korean J Hepatol 2012;18(3):309-315.
Published online September 25, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.3.309
Background/Aims

The aim of this study was to describe the types and causes of liver disease in patients from a single community hospital in Korea between April 2005 and May 2010.

Methods

A cohort of patients who visited the liver clinic of the hospital during the aforementioned time period were consecutively enrolled (n=6,307). Consistent diagnostic criteria for each liver disease were set by a single, experienced hepatologist, and the diagnosis of all of the enrolled patients was confirmed by retrospective review of their medical records.

Results

Among the 6,307 patients, 528 (8.4%) were classified as acute hepatitis, 3,957 (62.7%) as chronic hepatitis, 767 (12.2%) as liver cirrhosis, 509 (8.1%) as primary liver cancer, and 546 (8.7%) as a benign liver mass or other diseases. The etiologies in the acute hepatitis group in decreasing order of prevalence were hepatitis A (44.3%), toxic hepatitis (32.4%), other hepatitis viruses (13.8%), and cryptogenic hepatitis (9.1%). In the chronic hepatitis group, 51.2% of cases were attributed to viral hepatitis, 33.3% to nonalcoholic fatty liver disease, and 13.0% to alcoholic liver disease (ALD). Of the cirrhoses, 73.4% were attributable to viral causes and 18.1% to alcohol. Of the hepatocellular carcinoma cases, 86.6% were attributed to viral hepatitis and 11.6% to ALD. Among the benign tumors, hemangioma comprised 52.2% and cystic liver disease comprised 33.7%.

Conclusions

Knowledge of the current status of the type and cause of liver disease in Korea may be valuable as a basis for evaluating changing trends in liver disease in that country.

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Review

Hepatic neoplasm

Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period
Do Seon Song, Si Hyun Bae
Korean J Hepatol 2012;18(3):258-267.
Published online September 25, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.3.258

Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths in the world. There have been many advances in the diagnosis of HCC during the last ten years, especially in the imaging techniques. The Korean Liver cancer study group (KLCSG), European Association for the Study of the Liver (EASL), American Association for the Study of Liver disease (AASLD), and Asian-Pacific Association for the Study of Liver (APASL) have made and changed the HCC guidelines with the advances in the imaging techniques and according to the results of the researches on HCC. We reviewed the changes of the imaging guidelines in HCC diagnosis according to the advances in the imaging techniques. Further studies will be necessary to resolve the controversies in the diagnosis of HCC smaller than 1 cm in size.

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Clinical and Molecular Hepatology Elsewhere

Hepatic neoplasm

Noninvasive diagnosis of hepatocellular carcinoma
Byung Seok Kim
Korean J Hepatol 2012;18(2):245-247.
Published online June 26, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.2.245
  • 8,050 View
  • 75 Download

Original Article

Drug induced liver injury

The clinical features of drug-induced liver injury observed through liver biopsy: focus on relevancy to autoimmune hepatitis
Hye Young Ju, Jae Young Jang, Soung Won Jeong, Sung Ae Woo, Min Gyu Kong, Hee Yoon Jang, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, So Young Jin, Hong Soo Kim, Boo Sung Kim
Korean J Hepatol 2012;18(2):213-218.
Published online June 26, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.2.213
Background/Aims

Accurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH.

Methods

The clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2±12.8 years (mean±SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively.

Results

Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase levels were 662.2±574.8 U/L, 905.4±794.9 U/L, 12.9±10.8 mg/dL, 195.8±123.3 U/L, and 255.3±280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1±519.1 vs. 1043.3±600.5 U/L), globulin levels (2.7±0.4 vs. 3.3±0.5 g/dL), and prothrombin time (12.9±2.4 vs. 15.2±3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7±0.9 in the DILI group and 6.5±0.9 in the AIH group (P<0.001).

Conclusions

Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.

Citations

Citations to this article as recorded by  Crossref logo
  • Acute liver injury following methylprednisolone pulse therapy: 13 cases from a prospectively collected cohort
    Julian Allgeier, Sabine Weber, Rumyana Todorova, Jens Neumann, Alexander Gerbes
    European Journal of Gastroenterology & Hepatology.2022; 34(4): 457.     CrossRef
  • MODERN VIEW ON THE PROBLEM OF MEDICINAL LIVER LESIONS
    E. Yu Bibik, B. S Krivokolyisko, M. V Zolotarevskaya, O. A Churilin, Yu. S Venidiktova, N. G Zabolotnaya, N. G Samokish
    Journal of Volgograd State Medical University.2020; 17(4): 24.     CrossRef
  • VALUE OF TRANS-ABDOMINAL ULTRASOUND-GUIDED PERCUTANEOUS LIVER BIOPSY IN PATIENTS WITH FOCAL OR DIFFUSE LIVER LESIONS IN KURDISTAN CENTRE FOR GASTROENTEROLOGY AND HEPATOLOGY IN SULAIMANI CITY
    Dana Gharib, Mohammed Mohammed, Taha Al-Karboly, Heero Faraj, Kawa Mahmood, Nasr Qazi, Karok Salih, Omar Azeez
    JOURNAL OF SULAIMANI MEDICAL COLLEGE.2020; 10(2): 199.     CrossRef
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    Liping Guo, Lu Zhou, Na Zhang, Baoru Deng, Bangmao Wang
    Gastroenterology Research and Practice.2017; 2017: 1.     CrossRef
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    Kunal K Dalal, Thomas Holdbrook, Steven R Peikin
    World Journal of Hepatology.2017; 9(31): 1205.     CrossRef
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    Jinho Lee, Joon-Shik Shin, Me-riong Kim, Jang-Hoon Byun, Seung-Yeol Lee, Ye-sle Shin, Hyejin Kim, Ki Byung Park, Byung-Cheul Shin, Myeong Soo Lee, In-Hyuk Ha
    Journal of Ethnopharmacology.2015; 169: 407.     CrossRef
  • Autoimmune hepatitis
    Farhad Sahebjam, John M. Vierling
    Frontiers of Medicine.2015; 9(2): 187.     CrossRef
  • Clinical Features of Drug-induced Liver Injury According to Etiology
    Byoung Moo Lee, Woong Cheul Lee, Jae Young Jang, Pyoung Ahn, Jin Nyoung Kim, Soung Won Jeong, Eui Ju Park, Sae Hwan Lee, Sang Gyune Kim, Sang-Woo Cha, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim
    Journal of Korean Medical Science.2015; 30(12): 1815.     CrossRef
  • Autoimmune Hepatitis and Overlap Syndromes: Diagnosis and Management
    John M. Vierling
    Clinical Gastroenterology and Hepatology.2015; 13(12): 2088.     CrossRef
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    Agustin Castiella
    World Journal of Hepatology.2014; 6(4): 160.     CrossRef
  • 13,610 View
  • 140 Download
  • Crossref

Editorial

Hepatic neoplasm

Noninvasive diagnostic criteria for hepatocellular carcinoma
Han Chu Lee
Korean J Hepatol 2012;18(2):174-177.
Published online June 26, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.2.174

Citations

Citations to this article as recorded by  Crossref logo
  • LI-RADS for Diagnosing Hepatocellular Carcinoma in Patients with Noncirrhotic Chronic Hepatitis C
    Jihyun An, Rohee Park, Euichang Kim, Seong Kyun Na, Ha Il Kim, In-Hye Song, Young Seo Cho, Ji Hun Kang, Han Chu Lee, Seungbong Han, Jean-Charles Nault, Sang Hyun Choi, Ju Hyun Shim
    Radiology.2025;[Epub]     CrossRef
  • Novel Mahalanobis-based feature selection improves one-class classification of early hepatocellular carcinoma
    Ricardo de Lima Thomaz, Pedro Cunha Carneiro, João Eliton Bonin, Túlio Augusto Alves Macedo, Ana Claudia Patrocinio, Alcimar Barbosa Soares
    Medical & Biological Engineering & Computing.2018; 56(5): 817.     CrossRef
  • Angio-Computed Tomograph-Guided Immediate Lipiodol Computed Tomograph for Diagnosis of Small Hepatocellular Carcinoma Lesions during Transarterial Chemoembolization
    Feng-Yong Liu, Xin Li, Hong-Jun Yuan, Yang Guan, Mao-Qiang Wang
    Chinese Medical Journal.2018; 131(20): 2410.     CrossRef
  • Incidence and risk factors for surveillance failure in patients with regular hepatocellular carcinoma surveillance
    Dong Hyun Sinn, Jieun Yi, Moon Seok Choi, Dongil Choi, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Byung Chul Yoo
    Hepatology International.2013; 7(4): 1010.     CrossRef
  • 9,165 View
  • 58 Download
  • Crossref

The Korean Journal of Hepatology Elsewhere

Apoptosis and diagnosis of nonalcoholic steatohepatitis
Chang Wook Kim, Chang Don Lee
Korean J Hepatol 2011;17(3):247-249.
Published online September 30, 2011
DOI: https://doi.org/10.3350/kjhep.2011.17.3.247

Citations

Citations to this article as recorded by  Crossref logo
  • Lacticaseibacillus paracsei HY7207 Alleviates Hepatic Steatosis, Inflammation, and Liver Fibrosis in Mice with Non-Alcoholic Fatty Liver Disease
    Hyeon-Ji Kim, Hye-Jin Jeon, Dong-Gun Kim, Joo-Yun Kim, Jae-Jung Shim, Jae-Hwan Lee
    International Journal of Molecular Sciences.2024; 25(18): 9870.     CrossRef
  • 15-Lipoxygenase metabolites of α-linolenic acid, [13-(S)-HPOTrE and 13-(S)-HOTrE], mediate anti-inflammatory effects by inactivating NLRP3 inflammasome
    Naresh Kumar, Geetika Gupta, Kotha Anilkumar, Naireen Fatima, Roy Karnati, Gorla Venkateswara Reddy, Priyanka Voori Giri, Pallu Reddanna
    Scientific Reports.2016;[Epub]     CrossRef
  • 9,040 View
  • 47 Download
  • Crossref

Original Articles

Development and validation of a simple index system to predict nonalcoholic fatty liver disease
Young Jin Park, Jie Hyang Lim, Eun Ryoung Kwon, Hee Kyoung Kim, Myoung Chul Jung, Kyoung Hwan Seol, Woo Yong Noh, Na Eun Kim
Korean J Hepatol 2011;17(1):19-26.
Published online March 21, 2011
DOI: https://doi.org/10.3350/kjhep.2011.17.1.19
Background/Aims

Abdominal ultrasonography is useful for the detection and diagnosis of nonalcoholic fatty liver disease (NAFLD). The aims of this study were to establish a predictive model for the selection of subjects for abdominal ultrasonography for the diagnosis of NAFLD and to assess validity of the model.

Methods

The subjects included 901 people who visited the health examination center of the Busan Medical Center. We conducted multiple logistic regression analyses of potential risk factors to identify independent risk factors for NAFLD, and developed an index system.

Results

Four independent risk factors were identified. The index system was developed by assigning 1 clinical scoring point to approximately 0.7 logistic regression coefficients to each factor as follows: alanine aminotransferase/aspartate aminotransferase ratio >1.5 (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.21-4.07; P=0.010), 1 point; γ-glutamyl transpeptidase >50 (OR, 2.15; 95% CI, 1.13-4.07; P=0.019), 1 point; triglyceride >150 mg/dL (OR, 1.92; 95% CI, 1.14-3.24; P=0.015), 1 point; 23 kg/m2≤BMI<25 kg/m2 (OR, 3.68; 95% CI, 2.05-6.63; P<0.001), 2 points; and BMI 25 kg/m2 (OR, 7.65; 95% CI, 4.29-13.62; P<0.001), 3 points. The area under the receiver operating characteristics curve was 0.797 (95% CI, 0.751-0.842), and when 3 points was used as a cut-off value, the sensitivity and specificity were 71.7% and 75.9%, respectively.

Conclusions

NAFLD can be predicted through the clinical application of the index system established herein. If abdominal ultrasonography is used for high-risk patients, NAFLD will be diagnosed and managed in its early stage.

Citations

Citations to this article as recorded by  Crossref logo
  • Evaluation of ten diagnostic models for metabolic dysfunction-associated fatty liver disease in lean people living with HIV
    Wei Xu, Danping Liu, Renfang Zhang, Jun Chen, Yinzhong Shen
    BMC Infectious Diseases.2025;[Epub]     CrossRef
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    K.C. van Son, L.C. te Nijenhuis-Noort, S.C. Boone, D.O. Mook-Kanamori, A.G. Holleboom, P.R. Roos, H.J. Lamb, G. Alblas, M.J. Coenraad, F.R. Rosendaal, R. de Mutsert, M.E. Tushuizen
    Medicine.2024; 103(1): e34934.     CrossRef
  • Automated machine learning models for nonalcoholic fatty liver disease assessed by controlled attenuation parameter from the NHANES 2017–2020
    Lihe Liu, Jiaxi Lin, Lu Liu, Jingwen Gao, Guoting Xu, Minyue Yin, Xiaolin Liu, Airong Wu, Jinzhou Zhu
    DIGITAL HEALTH.2024;[Epub]     CrossRef
  • Diagnostic accuracy of blood biomarkers and non-invasive scores for the diagnosis of NAFLD and NASH: Systematic review and meta-analysis
    Daniela Contreras, Alejandra González-Rocha, Patricia Clark, Simón Barquera, Edgar Denova-Gutiérrez
    Annals of Hepatology.2023; 28(1): 100873.     CrossRef
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    Yuxiu Liu, Shiying Liu, Jiaofeng Huang, Yueyong Zhu, Su Lin
    Journal of Gastroenterology and Hepatology.2022; 37(5): 938.     CrossRef
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    Jiwon Kim, Minyoung Lee, Soo Yeon Kim, Ji-Hye Kim, Ji Sun Nam, Sung Wan Chun, Se Eun Park, Kwang Joon Kim, Yong-ho Lee, Joo Young Nam, Eun Seok Kang
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Prediction of compensated liver cirrhosis by ultrasonography and routine blood tests in patients with chronic viral hepatitis
Hong Sub Lee, Jai Keun Kim, Jae Youn Cheong, Eun Jin Han, So-Yeon An, Jun Ha Song, Yun Jung Jung, Sung Chan Jeon, Min Wook Jung, Eun-Jung Jang, Sung Won Cho
Korean J Hepatol 2010;16(4):369-375.
Published online December 31, 2010
DOI: https://doi.org/10.3350/kjhep.2010.16.4.369
Background/Aims

Liver biopsy is a standard method for diagnosis of liver cirrhosis in patients with chronic hepatitis. Because liver biopsy is an invasive method, non-invasive methods have been used for diagnosis of compensated liver cirrhosis in patients with chronic hepatitis. The current study was designed to evaluate the usefulness of ultrasonography and routine blood tests for diagnosis of compensated liver cirrhosis in patients with chronic viral hepatitis.

Methods

Two hundred three patients with chronic viral hepatitis who underwent liver biopsy were included in this study and ultrasonography and routine blood tests were analyzed retrospectively. Ultrasonographic findings, including surface nodularity, parenchyma echogenecity, and spleen size, were evaluated. The diagnostic accuracy of ultrasonography and routine blood tests were examined.

Results

Discriminant analysis with forward stepwise selection of variables showed that liver surface nodularity, platelet count, and albumin level were independently associated with compensated liver cirrhosis (p<0.05). Cross-tabulation revealed that the following 4 variables had >95% specificity: platelet count <100,000 /uL; albumin level <3.5 g/dL; INR >1.3; and surface nodularity. If at least one of the four variables exists in a patient with chronic viral hepatitis, we can predict liver cirrhosis with 90% specificity and 61% sensitivity.

Conclusions

These results suggest that four variables (platelet count <100,000 /uL, albumin level <3.5 g/dL, INR >1.3, and surface nodularity) can be used for identification of liver cirrhosis in patients with chronic viral hepatitis with high specificity.

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Validity and reliability of the nonalcoholic fatty Liver diseases activity score (NAS) in Korean NAFLD patients and its correlation with clinical factors
Kyung-Hun Lee, M.D., Sang Hoon Park, M.D., Yu Jin Kim, M.D., Kyung Rim Huh, M.D., Kwang Seon Min1, M.D., Sun-Young Jun1, M.D., Kyoung Oh Kim, M.D., Cheol Hee Park, M.D., Taeho Hahn, M.D., Kyo-Sang Yoo, M.D., Jong Hyeok Kim, M.D., Myung-Seok Lee, M.D., Choong Kee Park, M.D.
Korean J Hepatol 2010;16(1):29-37.
Published online March 26, 2010
DOI: https://doi.org/10.3350/kjhep.2010.16.1.29
Background
/Aim: Nonalcoholic steatohepatitis (NASH) is commonly diagnosed using the semi-quantitative grading and staging system proposed by Brunt et al. in 1999. The Pathology Committee of the NASH established the nonalcoholic fatty liver diseases (NAFLD) activity score (NAS) in 2005. The aim of this study was to elucidate the validity and reliability of the NAS in Korean NAFLD patients. Methods: Fifty-six patients on whom sonography-guided liver biopsy for well-defined NAFLD was performed between 1999 and 2007 were identified retrospectively. Two pathologists evaluated each biopsy sample. NAFLD was evaluated using both the grading system developed by Brunt et al. and the NAS. Each pathologist was blinded to the patients` clinical data and scored independently. We evaluated the body mass index (BMI), liver enzymes, lipid profile, peripheral insulin resistance, leptin, insulin/c-peptide ratio, ferritin, and fasting blood glucose. Results: The patients were aged 32.1±12.5 years (mean±SD) and comprised 44 males (78.6%). Patients with different grades at the two grading systems had mild steatosis or ballooning changes with fibrosis, and 36.6% of them were borderline cases (NAS of 3 or 4). The interobserver agreement on diagnostic category was 0.748 (P<0.001) for the NAS (using weighted κ statistics). Elevated fasting glucose, ALT, and triglyceride were associated with the NAS. Conclusions: The simple and reproducible NAS was found to be a useful pathologic grading system in Korean NAFLD patients. However, the proportion of borderline cases based on the NAS was high. The "wait and see" strategy is necessary for evaluating the long-term prognosis. (Korean J Hepatol 2010;16:29-37)

Citations

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Special Contribution

Special Contribution : Practice guidelines for management of hepatocellular carcinoma 2009
Korean Liver Cancer Study Group and National Cancer Center, Korea
Korean J Hepatol 2009;15(3):391-423.
Published online September 30, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.3.391
Hepatocellular carcinoma (HCC) is a major cancer in Korea, typically has a poor prognosis, and constitutes the majority of primary hepatic malignancies. It is the number one cause of death among people in their 50s in Korea. The five-year survival rate of liver cancer is poor; at 18.9%. Efforts to increase the survival rate through early diagnosis of HCC and optimal treatments are keenly needed. Western guideline for the management of HCC were developed, but these guidelines are somewhat unsuitable for Korean patients. Thus, the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC), Korea jointly produced the Clinical Practice Guidelines for HCC for the first time in Korea in 2003. Owing to medical advances over the following six years, diagnosis and treatment of HCC has changed considerably. As more national and foreign data are accumulated, KLCSG and NCC, Korea recently revised the Clinical Practice Guidelines for HCC. Forty or more specialists in the field of hepatology, general surgery, radiology and radiation oncology participated, and meticulously reviewed national and foreign papers, and collected opinions through advisory committee conferences. These multidisciplinary, evidence-based guidelines summarized diagnosis, surgical resection, liver transplantation, local treatments, transarterial chemoembolization, radiation therapy, chemotherapy, preemptive antiviral treatments, and response evaluation of HCC. These Korean guidelines are expected to be useful for clinical management of and research on HCC. (Korean J Hepatol 2009;15:391-423)

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Original Articles

Liver Stiffness Measurement for the Diagnosis of Hepatic Fibrosis in Patients with Chronic Viral Hepatitis
Joon Koo Kang, M.D.1, Jae Youn Cheong, M.D.1, Sung Won Cho, M.D.1, Jin Hui Cho, M.D.1, Jin Sun Park, M.D.1, Yeong Bae Kim, M.D.2, Dong Joon Kim, M.D.3, Seong Gyu Hwang, M.D.4, Jin Mo Yang, M.D.5, Young Nyun Park, M.D.6
Korean J Hepatol 2007;13(4):521-529.
Published online December 20, 2007
DOI: https://doi.org/10.3350/kjhep.2007.13.4.521
Background/Aims
FibroScanⓇ is a new medical device that noninvasively measures liver stiffness. The aim of this study was to assess the accuracy of the liver stiffness measurement by FibroScanⓇ for making the diagnosis of liver fibrosis in patients with chronic viral hepatitis. Methods: We studied 103 patients with chronic viral hepatitis B or C and they underwent FibroScanⓇ and liver biopsy between October 2005 and August 2006. Liver fibrosis was staged on a 0-4 scale according to the Korean Society of Pathologists Scoring System. The diagnostic accuracy was assessed by analysis of the receiver operator characteristics (ROC). Results: The liver stiffness was 3.5-57.1 kPa (mean: 11.8, SD: 8.9). The mean value of liver stiffness in each fibrosis stage group (F1, F2, F3 and F4) was 5.8±1.8 kPa, 11.3±6.8 kPa, 11.8±6.0 kPa and 23.4±16.5 kPa, respectively. Liver stiffness measured by FibroScanⓇ showed reliable correlation with the liver fibrosis stage as confirmed by liver biopsy (r=0.56, p<0.001). The AUROC (95% CI) of ≥ F2, ≥ F3 and F4 was 0.93 (0.86-0.99), 0.72 (0.62-0.82) and 0.80 (0.67-0.92), respectively. The sensitivity and specificity of 7.5 kPa, which was the cutoff value for ≥ F2, was 84% and 90%, respectively. Conclusions: FibroScanⓇ is a reliable method for the diagnosis of significant fibrosis (≥ F2) and cirrhosis in patients with chronic liver disease. The liver stiffness measurement by FibroScanⓇ showed good diagnostic performance for significant fibrosis. (Korean J Hepatol 2007;13:521-529)

Citations

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Effectiveness of Early Detection among the High Risk Group of Hepatocellular Carcinoma by Ultrasound Screening Test
Jeong Il Jeong, Kwang Hyub Han, Byung Hyun Choe, Sang Hoon Ahn, Dong Ki Kim, Chung Mo Nam, Jae Bock Chung, Chae Yoon Chon and Young Myoung Moon
Korean J Hepatol 1998;4(4):330-345.
Backgroung/Aims : The prognosis of primary hepatocellular carcinoma is extremely poor because of its large size, portal vein thrpombosis, extrahepatic metastasis and underlying liver cirrhosis. The aim, of this study is to evaluate the usefulness of ultrasound screening test for early detection of hepatocellular carcinoma in high-ridk populations. Methods : We analysed 119 patients who were diagnosed with hepatocellular carcinoma by ultrasonography screening test in Yonsei University Severance Hospital from the period of January 1990 to December 1996. Result : The mean follow-up duration to the diagnosis of hepatocellular carcinoma was 30 months (range 3-75). The number of patients with single lesion was 89(75%). The mean diameter of the tumor was 3.0 cm (range 1-10) , 82 patients (70%) had masses measured less than 3cm in diameter. The Number of patients with elevated serum alphafetoprotein level above 400ng/ml was 29(25%). The median survival was 28 months in screening group, significant compared with 7 months in control group (p<0.001). Conclusions : Ultrasound follow-up in high-ridk group of hepatocellular carcinoma mede it possible to detect small tumors in a high percentage of cases. This may lead to an increase in the number of potentially curable tumors and hence an increase in the overall survival rate. So ultrasound screening test is important in the high-ridk group of hepatocellular carcinoma. ( Korean J Hepatol 1998;4:330-345)
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A Clinical Study on Small Hepatocellular Carcinoma
Kyoung Soo Kim, M.D., Soon Ho Um, M.D., Ho Sang Ryu, M.D., Mi Ra Park , Jae Won Lee , Dong Gyu Park, M.D., Sung Joon Lee, M.D., Goo Lee, M.D., Kwang Hee Kim, M.D., Yoon Tae Jin, M.D., Hoon Jai Chun, M.D., Chi Wook Song, M.D., Sang Woo Lee, M.D., Jai Hyun Choi, M.D., Chang Duck Kim, M.D., Hyun Jin Hai, M.D., Yoon Hwan Kim, M.D. and Sung Ok Seo, M.D.
Korean J Hepatol 1998;4(4):365-380.
Background
/ Aims : Cases of small hepatocellular carcinoma (HCC) have been increasing with the progress of diagnostic methods . In t his study the screening methods for early diagnos is of HCC were re-evaluated, and comparative ther apeutic analyses were perfomed. Methods : A total of 110 pat ients with small HCC (< 5 cm and < 4 nodules ) were retrospectively analyzed. The patients were divided into four treatment groups ; unt reated group (No T x, n=12), transarterial-oily-chemoembolization group (TOCE, n=43), combined treatment group of percutaneous ethanol injection and TOCE (CEI, n=22), OP group ( OP, n=33). Results : Small HCC occupied 22.6% of t ot al HCC cases . Only one thir d of small HCC cases were detected during the regular screening. In this group, Alpha- fet oprotein as say pr ovided a diagnostic clue in 50% of cases, ultras onography in 71%, and the combination of both in 88%. Five year s ur vival rat e and 5- year non- recurrence rate in small HCC was 29% and 37% respectively. Comparative ther apeutic analys es showed t hat CEI and OP gave a bet t er s ur vival t han T OCE in Child gr ade A. CEI prolonged survival in Child grade B wher eas TOCE did not . Only TOCE was tried and did not improve the survival in Child grade C. Conclus i on : 1) A more strict screening is needed in high risk group of HCC. 2) As a first line of treatment in small HCC, OP or CEI can be selected in Child grade A, and CEI in Child grade B. In Child grade C, a less invasive treatment (PEIT , microwave coagulat ion therapy) should be investigated. (Korean J Hepatol 1998;4:365 380)
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Validation of International Autoimmune Hepatitis Group Scoring System for Dianosis of Type 1 Autoimmune Hepatitis in Korea
Saera Jung, M.D., Han Chu Lee, M.D., Young Hwan Park, M.D., Sang Soo Lee, M.D., Hee Gon Song, M.D., Seung Il Pyo, M.D., Byung-Cheol Song, M.D.* , Young-Hwa Chung, M.D., Yung Sang Lee, M.D., and Dong Jin Suh, M.D.
Korean J Hepatol 2002;8(1):35-43.
Background/Aims
There are no pathognomonic features of autoimmune hepatitis (AIH). Its diagnosis requires the exclusion of various other conditions. The aim of this study was to validate indirectly the International Autoimmune Hepatitis Group (IAHG) scoring system in diagnosing AIH. Methods: Twenty-six patients with Type 1 AIH and female patients with chronic hepatitis B (n=34), chronic hepatitis C (n=25), or toxic hepatitis (n=13) were evaluated according to 9 categories of pretreatment minimum required parameters proposed by IAHG. Aggregate scores of AIH to those of non-AIH groups, which were assessed before and after extracting the proportions of etiologic factors, were also compared and evaluated. Results: While aggregate scores of non-AIH groups, before extracting the proportions of etiologic factors, were 5.2±1.8, 5.6±1.1, and 7.4±1.2 in that order, those of AIH groups were 12.8±1.7. These were significantly higher than those of non-AIH groups (p<0.01). All patients in AIH groups and only 1 patient in a non-AIH group showed aggregate scores of more than 10. Aggregate scores after extracting the proportions of etiologic factors were more than 4 in all, except 2, patients. These should have been consistent with 10 if there were no etiologic factors in non-AIH groups. Conclusion: The IAHG scoring system might have a relatively excessive importance to the scores of categories excluding distinct etiologies from AIH. It might be difficult to differentiate AIH from chronic liver diseases of indistinct cause based on the IAHG scoring system.(Korean J Hepatol 2002;8:35-43)
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Clinical Experience of 48 Acute Toxic Hepatitis Patients
Jeong Chul Seo, M.D., Won Joong Jeon, M.D., Sung Soon Park, M.D., Seok Hyung Kim, M.D.1, Ki Man Lee, M.D., Hee Bok Chae, M.D., Seon Mee Park, M.D. and Sei Jin Youn, M.D.
Korean J Hepatol 2006;12(1):74-81.
Background/Aims
Although many individual cases of toxic hepatitis have been reported in Korea, there are few comprehensive systematic studies on acute toxic hepatitis. The first aim of this study is to investigate the frequency and clinical characteristics of acute toxic hepatitis patients. The second aim of this study is to investigate the efficacy of steroid therapy for immunoallergic idiosyncrasy. Methods: Between March 1998 and March 2004 forty eight patients were included in this study. The medical records were reviewed retrospectively. Acute toxic hepatitis was diagnosed by score of more than 3 in RUCAM criteria. All the patients were tested for hepatitis A, B and C. Other tests included antibodies to CMV and EBV, ANA, AMA and SMA. Results: Seventy-three percent of the patients were female and the mean age of the patients was 47. Twenty cases of acute toxic hepatitis (42%) were related to prescribed medications. The other causes were herbs (35%) and traditional therapeutic preparations (23%). Common symptoms were jaundice (35%), fatigue (10%), fever (9%) and abdominal pain (9%). The biochemical pattern of hepatotoxicity was divided into three groups: hepatocellular (81%), mixed (13%), and cholestatic types (6%). Three patients who have prolonged and severe jaundice were classified into immunoallergic idiosyncrasy based upon clinical and histologic findings. Prednisolone was prescribed in all three cases whose bilirubin levels had been higher than 15 mg/dL for at least 7 days. Jaundice and the laboratory findings rapidly improved within 8 days since the treatment began. Conclusions: In a demographic point of view, most patients of acute toxic hepatitis were middle aged women. Jaundice was the most commonly observed symptom. Prescribed drugs were the most common cause of acute toxic hepatitis. Although most cases of toxic hepatitis will recover with supportive care after cessation of the causative agent, steroid treatment may be helpful for the patients with severe jaundice patients who have immunoallergic idiosyncrasy. (Korean J Hepatol 2006;12:74-81)
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Case Report

Toxic Hepatitis Associated with Carp Juice Ingestion
Hye Suk Son , Guil Sun Kim , Seung Woo Lee , Sang Bum Kang , Jong Tae Back , Soon Woo Nam , Dong Soo Lee , Byung Min Ahn
Korean J Hepatol 2006;12(1):103-106.
The potential hepatotoxicity of herbal remedies and/or health foods is usually ignored in daily life. There have been cases showing the toxic hepatitis and renal failure associated with the ingestion of raw carp bile. We experienced a case of toxic hepatitis without any evidence of renal failure that was associated with carp juice ingestion. The clinical manifestations were characterized by nausea and vomiting after the ingestion of carp juice for 3 months. The diagnosis of toxic hepatitis was made on the basis of the patient’s history, laboratory data, RUCAM (Russel Uclaf Causality Assessment) and the results of ultrasonography guided liver biopsy. The patient showed rapid improvement after instituting supportive therapy. (Korean J Hepatol 2006; 12:103-106)
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Review
Wilson Disease: an Update
Jeong Kee Seo
Korean J Hepatol 2006;12(3):333-363.
Wilson disease (WD) is an autosomal recessive disorder of copper transport that results in accumulation of copper primarily in the liver, the brain and the cornea. WD is the most common inherited liver disease with the prevalence of 1: 37,000 in the pediatric population in Korea. Mutations in the ATP7B gene cause failure of copper excretion into the bile and a defective incorporation of copper into ceruloplasmin. More than 300 mutations in the ATP7B gene have been described so far. Mutations differ between ethnic groups. The p.R778L (an allele frequency of 37%), p.A874V (13%), p.L1083F (8%) and p.N1270S (6%) are the common major mutations in Korea. Conflicting results on genotype/phenotype correlations of the most common mutations have been reported in various countries. There seems to be no correlation between the R778L mutation and age of onset or clinical manifestations in Korean patients. None of the laboratory parameters alone allows a definite diagnosis of WD. In a nation-wide survey of WD, low serum ceruloplasmin (<20 mg/dL), high 24 hour urine copper (>100 μg), high hepatic copper content (>250 μg/g of dry liver) and Kayser-Fleischer rings were found in 96%, 86%, 88%, and 73% of the 550 Korean patients respectively. A combination of any two of the above 4 laboratory findings is strong support for a diagnosis of WD. For the last couple of years, genetic testing has been playing an increasingly important role in diagnosing WD. Direct DNA sequencing did confirm WD in 98% of the Korean patients. Two mutations were detected in 70% and one mutation in 28% of the patients who showed characteristic biochemical and clinical findings of WD. Genetic testing, either by haplotype analysis or by mutation analysis, is the only reliable tool for differentiating heterozygote carriers from affected asymptomatic patients. The agents of the first choice among chelators and zinc in specific clinical situations of WD is still a matter of debate. Because of frequent side effects and initial neurologic deterioration of penicillamine therapy, less toxic trientine or zinc has gradually replaced penicillamine over the past few years. Trientine or tetrathiomolybdate has been increasingly recommended as the first-line treatment for neurologic WD. Currently, liver transplantation is not recommended as primary treatment for neurologic WD. Recently published data show that initial zinc therapy for asymptomatic/presymptomatic patients and maintenance zinc therapy in patients after long term chelation are safe and effective. Further researches and the new guidelines on the proper management of patients with WD are needed.
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