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Hepatic neoplasm

Citations

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  • Reply to correspondence on “Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting”
    Antonio Bertoletti, Anthony T Tan
    Clinical and Molecular Hepatology.2025; 31(1): e113.     CrossRef
  • 3,722 View
  • 56 Download
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Review

Steatotic liver disease

Precision medicine and nucleotide-based therapeutics to treat steatotic liver disease
Andrea Caddeo, Stefano Romeo
Clin Mol Hepatol 2025;31(Suppl):S76-S93.
Published online August 5, 2024
DOI: https://doi.org/10.3350/cmh.2024.0438
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex multifactorial disease and becoming the leading cause of liver-related morbidity and mortality. MASLD spans from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), that may progress to cirrhosis and hepatocellular carcinoma (HCC). Genetic, metabolic, and environmental factors strongly contribute to the heterogeneity of MASLD. Lifestyle intervention and weight loss represent a viable treatment for MASLD. Moreover, Resmetirom, a thyroid hormone beta receptor agonist, has recently been approved for MASLD treatment. However, most individuals treated did not respond to this therapeutic, suggesting the need for a more tailored approach to treat MASLD. Oligonucleotide-based therapies, namely small-interfering RNA (siRNA) and antisense oligonucleotide (ASO), have been recently developed to tackle MASLD by reducing the expression of genes influencing MASH progression, such as PNPLA3 and HSD17B13. Here, we review the latest progress made in the synthesis and development of oligonucleotide-based agents targeting genetic determinants of MASH.

Citations

Citations to this article as recorded by  Crossref logo
  • NSD2 exacerbates metabolic dysfunction-associated steatotic liver disease progression by suppressing TFEB-mediated autophagy-lysosomal pathway
    Yuan Qiao, Yijia Zhang, Cuiting Sun, Qi Jin, Peng Qu, Zecheng Li, Yang Qiu, Hua Meng, Dantao Peng, Liang Peng
    Metabolism.2026; 174: 156416.     CrossRef
  • Rodent model of metabolic dysfunction‐associated fatty liver disease: a systematic review
    Xiao‐Shan Cui, Hong‐Zheng Li, Liang Li, Cheng‐Zhi Xie, Jia‐Ming Gao, Yuan‐Yuan Chen, Hui‐Yu Zhang, Wei Hao, Jian‐Hua Fu, Hao Guo
    Journal of Gastroenterology and Hepatology.2025; 40(1): 48.     CrossRef
  • Role of PNPLA3 in Hepatic Stellate Cells and Hepatic Cellular Crosstalk
    Maria Castanho Martins, Emmanuel Dauda Dixon, Giulia Lupo, Thierry Claudel, Michael Trauner, Krista Rombouts
    Liver International.2025;[Epub]     CrossRef
  • Novel Therapies for Nonalcoholic Steatohepatitis (NASH) and Cardiovascular Risk Reduction
    Tarun Biswas, Angelica Lehker, Debabrata Mukherjee
    Cardiovascular & Hematological Disorders-Drug Targets.2025; 24(4): 211.     CrossRef
  • Liver-specific inactivation of Cideb improves metabolic profiles and ameliorates steatohepatitis and fibrosis in animal models for MASH
    Jianhua Zhang, Xujie Liu, Xian Jin, Xudong Mao, Xueli Xu, Xing Zhang, Ke Shang, Yuan Xu, Yanhuan Zhang, Guofeng Meng, Ming Yue, Guoqing Cai, Song Yang, Jinyu Huang, Jianwu Fang, Ling Pan, Lei Jiang, Stella Shi, Jianyong Shou
    Pharmacological Research.2025; 214: 107664.     CrossRef
  • Circadian control of hepatic ischemia/reperfusion injury via HSD17B13-mediated autophagy in hepatocytes
    Hui Wang, Meina Guo, Baoyin Ren, Haibo Zhang, Jiayang Zhang, Rongfang Qiao, Lei Qian, Jingwen Zhu, Shuying Zhang, Wen Su, Xiaoyan Zhang, Guangrui Yang, Youfei Guan, Lihong Chen
    Journal of Hepatology.2025; 83(3): 750.     CrossRef
  • Reversed role of CD36 deficiency in high-fat diet or methionine/choline-deficient diet-induced hepatic steatosis and steatohepatitis
    Wenya Zhu, Jialing Ma, Tingting Zhang, Mengmeng Zhu, Yajun Duan, Xiaoxiao Yang, Yuanli Chen
    Frontiers in Pharmacology.2025;[Epub]     CrossRef
  • Hepatocyte nuclear factor 4-Alpha: a key regulator in liver carcinogenesis
    Hayam Hamdy, Chang Shen, Jiashun Xu, Die Fan, Yiwen Zhang, Hui Li, Yonglong Wei, Jianwei Sun
    Cellular Oncology.2025; 48(4): 885.     CrossRef
  • Targeting CIDEB alleviates liver steatosis and fibrosis in mouse MASH models
    Yingying Lin, Fushun Fan, Zhenxian Mo, Ziyang Huang, Minhua Zhou, Yaru Ma, Chuiwen Qian, Yifei Wang, Changgeng Qian, Xinjian Liu
    Molecular Therapy Nucleic Acids.2025; 36(2): 102567.     CrossRef
  • Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Narrative Review
    Tatsuo Kanda, Reina Sasaki-Tanaka, Hiroyuki Abe, Naruhiro Kimura, Tomoaki Yoshida, Kazunao Hayashi, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai
    International Journal of Molecular Sciences.2025; 26(11): 5164.     CrossRef
  • Gelsolin's Protective Role in MASH through F‐Actin Regulation and P53 Degradation
    Yiwei Lu, Tong Ji, Zhichao Ye, Jianing Yan, Chao Wang, Jiachen Chen, Ziyang Jin, Yongji Zhu, Xiujun Cai, Yifan Wang
    Advanced Science.2025;[Epub]     CrossRef
  • Emerging therapies and real-world application of metabolic dysfunction-associated steatotic liver disease treatment
    Hee Yeon Kim, Mary E. Rinella
    Clinical and Molecular Hepatology.2025; 31(3): 753.     CrossRef
  • Multi-omics reveals total flavones from Abelmoschus manihot (L.) Medik. [Malvaceae] ameliorate MAFLD via PI3K/AKT/mTOR-mediated autophagy
    Chao Lv, Lei Zhao, Jiani Hou, Hongyin Sun, Zhongsha Li, Yuesong Wu, Peizheng Shi, Yaping Xiao, Yunjin Xie, Wei Su, Mingzhu Yin
    Frontiers in Pharmacology.2025;[Epub]     CrossRef
  • The Distribution and Survival Association of Genetic Polymorphisms in Thai Patients with Hepatocellular Carcinoma According to Underlying Liver Disease
    Theint Cho Zin Aung, Bootsakorn Boonkaew, Maneerat Chayanupatkul, Kittiyod Poovorawan, Natthaya Chuaypen, Pisit Tangkijvanich
    Genes.2025; 16(7): 808.     CrossRef
  • Editorial: Time to Genotype—Genetic Risk and Prognosis in Steatotic Liver Disease
    Rosellina M. Mancina, Stefano Romeo
    Alimentary Pharmacology & Therapeutics.2025; 62(8): 841.     CrossRef
  • Human genetics of steatotic liver disease: insights into insulin resistance and lipid metabolism
    Rosellina M. Mancina, Luca Valenti, Stefano Romeo
    Nature Metabolism.2025; 7(11): 2199.     CrossRef
  • Lysosome-Targeting Chimeras: Design, Mechanisms, and Degradation of “Rogue” Proteins
    Muneeb Ur Rehman, Xinxi Wu, Qun Chen, Ziwei Liu, Sihui Long
    Bioorganic Chemistry.2025; 167: 109249.     CrossRef
  • Pharmacotherapy of Liver Fibrosis and Hepatitis: Recent Advances
    Liangtao Zhao, Haolan Tang, Zhangjun Cheng
    Pharmaceuticals.2024; 17(12): 1724.     CrossRef
  • 9,884 View
  • 508 Download
  • 14 Web of Science
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Original Article

Viral hepatitis

Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients
Xiaoning Wu, Xiaoqian Xu, Jialing Zhou, Yameng Sun, Huiguo Ding, Wen Xie, Guofeng Chen, Anlin Ma, HongXin Piao, Bingqiong Wang, Shuyan Chen, Tongtong Meng, Xiaojuan Ou, Hwai-I Yang, Jidong Jia, Yuanyuan Kong, Hong You
Clin Mol Hepatol 2023;29(3):747-762.
Published online May 10, 2023
DOI: https://doi.org/10.3350/cmh.2023.0121
Background/Aims
Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT).
Methods
Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test.
Results
The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis.
Conclusions
The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Citations

Citations to this article as recorded by  Crossref logo
  • Racing toward the future of chronic hepatitis B management: Achieving functional cure and enhancing hepatocellular carcinoma surveillance through precision medicine
    Yaru Shi, Rong Fan
    Interdisciplinary Medicine.2025;[Epub]     CrossRef
  • La prise en charge de l'hépatite B chronique: mise à jour 2025 des lignes directrices de l'Association canadienne pour l'étude du foie et de l'Association pour la microbiologie médicale et l'infectiologie Canada
    Carla Osiowy, Fernando Alvarez, Carla S. Coffin, Curtis L. Cooper, Scott K. Fung, Hin Hin Ko, Sébastien Poulin, Jennifer van Gennip
    Canadian Liver Journal.2025; 8(2): 402.     CrossRef
  • The management of chronic hepatitis B: 2025 Guidelines update from the Canadian Association for the Study of the Liver and Association of Medical Microbiology and Infectious Disease Canada
    Carla Osiowy, Fernando Alvarez, Carla S Coffin, Curtis L Cooper, Scott K Fung, Hin Hin Ko, Sébastien Poulin, Jennifer van Gennip
    Canadian Liver Journal.2025; 8(2): 368.     CrossRef
  • Prediction Model for Familial Aggregated HBV‐Associated Hepatocellular Carcinoma Based on Serum Biomarkers
    Linmei Zhong, Guole Nie, Qiaoping Wu, Honglong Zhang, Haiping Wang, Jun Yan
    Cancer Reports.2025;[Epub]     CrossRef
  • LEAST as a novel prediction model of hepatocellular carcinoma development in patients with chronic hepatitis B: a multi-center study
    Jingjing Song, Jie Li, Zhigang Ren, Wen Xie, Jinhua Shao, Xiaoxiao Zhang, Yang Zhou, Fajuan Rui, Xiaoqing Wu, Qiuling Wang, Zuxiong Huang, Chao Sun, Yuemin Nan
    BMC Medicine.2025;[Epub]     CrossRef
  • Validation of the Texas Hepatocellular Carcinoma Risk Index Predictive Model for Hepatocellular Carcinoma in Asian Cohort
    Jeong-Ju Yoo, Young-Gi Song, Ji Eun Moon, Young Seok Kim, Sang Gyune Kim
    Clinical Gastroenterology and Hepatology.2024; 22(9): 1953.     CrossRef
  • Risk predictive model for the development of hepatocellular carcinoma before initiating long‐term antiviral therapy in patients with chronic hepatitis B virus infection
    Junjie Chen, Tienan Feng, Qi Xu, Xiaoqi Yu, Yue Han, Demin Yu, Qiming Gong, Yuan Xue, Xinxin Zhang
    Journal of Medical Virology.2024;[Epub]     CrossRef
  • Correspondence to editorial on “Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients”
    Xiaoqian Xu, Hong You, Jidong Jia, Yuanyuan Kong
    Clinical and Molecular Hepatology.2024; 30(4): 994.     CrossRef
  • Decreasing performance of HCC prediction models during antiviral therapy for hepatitis B: what else to keep in mind: Editorial on “Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B pati
    Beom Kyung Kim
    Clinical and Molecular Hepatology.2024; 30(4): 656.     CrossRef
  • Reply to correspondence on “Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients”
    Beom Kyung Kim
    Clinical and Molecular Hepatology.2024; 30(4): 1044.     CrossRef
  • 6,472 View
  • 174 Download
  • 9 Web of Science
  • Crossref

Review

Viral hepatitis

Hepatitis B core-related antigen: A novel and promising surrogate biomarker to guide anti-hepatitis B virus therapy
Takako Inoue, Takehisa Watanabe, Yasuhito Tanaka
Clin Mol Hepatol 2023;29(4):851-868.
Published online March 9, 2023
DOI: https://doi.org/10.3350/cmh.2022.0434
The current requirement for biomarkers to detect hepatitis B virus (HBV) infection is polarized. One is a fully-automated and highly sensitive measurement system; the other is a simple system for point-of-care testing (POCT) in resource-limited areas. Hepatitis B core-related antigen (HBcrAg) reflects intrahepatic covalently closed circular DNA and serum HBV DNA. Even in patients with undetectable serum HBV DNA or HBsAg loss, HBcrAg may remain detectable. Decreased HBcrAg levels are associated with reduction of the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B. Recently, a fully-automated, novel high-sensitivity HBcrAg assay (iTACT-HBcrAg, cut-off value: 2.1 logIU/mL) has been developed. This attractive assay has been released in Japan very recently. iTACT-HBcrAg can be useful for monitoring HBV reactivation and prediction of HCC occurrence, as an alternative to HBV DNA. Moreover, monitoring HBcrAg may be suitable for determining the therapeutic effectiveness of approved drugs and novel drugs under development. Presently, international guidelines recommend anti-HBV prophylaxis for pregnant women with high viral loads to prevent mother-to-child transmission of HBV. However, >95% of HBV-infected individuals live in countries where HBV DNA quantification is not available. Worldwide elimination of HBV needs the scaling-up of examination and medication services in resource-limited areas. Based on this situation, a rapid and easy HBcrAg assay as a POCT is valuable. This review provides the latest information regarding the clinical use of a new surrogate marker, HBcrAg, in HBV management, based on iTACT-HBcrAg or POCT, and introduces novel agents targeting HBV RNA/protein.

Citations

Citations to this article as recorded by  Crossref logo
  • Rapid test for hepatitis B core-related antigen to identify people living with hepatitis B having high viral load in Cameroon
    Richard Njouom, Alassane Ndiaye, Abdou Fatawou Modiyinji, Frederic Lissock, Jeanne Perpétue Vincent, Masaya Baba, Naoki Yamamoto, Atsushi Kaneko, Katsumi Aoyagi, Naofumi Hashimoto, Mari Nagai, Masato Ichikawa, Tetsuo Miura, Wataru Sugiura, Yasuhito Tanaka
    Virology.2025; 602: 110316.     CrossRef
  • Achieving chronic hepatitis B functional cure: Factors and potential mechanisms
    Jiarui Zheng, Zilong Wang, Linxiang Huang, Zixuan Qiu, Yandi Xie, Suzhen Jiang, Bo Feng
    Virus Research.2025; 351: 199507.     CrossRef
  • Observational pilot study of switching from entecavir to tenofovir alafenamide in patients with chronic hepatitis B
    Takuya Matsubara, Satoru Hagiwara, Naoshi Nishida, Naoya Omaru, Akihiro Yoshida, Tomoki Yamamoto, Yoriaki Komeda, Mamoru Takenaka, Masatoshi Kudo
    Scientific Reports.2025;[Epub]     CrossRef
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    Qiyao Wei, Jing Zhao
    BMC Gastroenterology.2025;[Epub]     CrossRef
  • Antiviral Therapy-Induced Changes in Long Non-Coding RNA Expression Profiles in Umbilical Cord Blood and Placental Tissues of Hepatitis B Virus-Infected Pregnant Women
    Cuimin Wang, Yuting Huang, Lanfeng Li, Xizhen Huang, Yin Huang, Xiang Fang, Yu Long
    International Journal of Women's Health.2025; Volume 17: 835.     CrossRef
  • Editorial: How to Interpret Clinical Impact of Viral Replication Activity for Postoperative Recurrence of HBV‐Related HCC
    Beom Kyung Kim
    Alimentary Pharmacology & Therapeutics.2025; 61(10): 1717.     CrossRef
  • Editorial: How to Interpret Clinical Impact of Viral Replication Activity for Postoperative Recurrence of HBV‐Related HCC—Authors' Reply
    Subin Heo, Won‐Mook Choi
    Alimentary Pharmacology & Therapeutics.2025; 61(10): 1719.     CrossRef
  • HBcrAg Dynamic Change During Treatment Predicts HBsAg Loss in Pediatric Patients With Chronic Hepatitis B
    Ling Ye, Wenxian Ouyang, Yingping Gu, Zhenzhen Yao, Xin Lai, Sisi Li, Meng Yang, Songxu Peng
    Journal of Medical Virology.2025;[Epub]     CrossRef
  • Unraveling Demographic Patterns in Hepatitis B Clinical and Laboratory Profiles: Insights From a Ghanaian Cohort: A Retrospective Study
    Napoleon Bellua Sam, Saeed Folorunsho Majeed, Adams Dramani
    Health Science Reports.2025;[Epub]     CrossRef
  • Future Perspectives of Liver Research in the Asia‐Pacific Region: Focus on Hepatitis B and C
    Beom Kyung Kim
    Journal of Gastroenterology and Hepatology.2025; 40(8): 1855.     CrossRef
  • Head‐to‐Head Comparison of Long‐Term HCC Risk of Antivirals‐Treated Versus Untreated Low‐Level Viremia in HBV‐Compensated Cirrhosis
    Nobuharu Tamaki, Daniel Q. Huang, Hyung Woong Lee, Soo Young Park, Yu Rim Lee, Dong Hyun Sinn, Tae Seop Lim, Hiroyuki Marusawa, Seng Gee Lim, Hironori Ochi, Masahiko Kondo, Yasushi Uchida, Haruhiko Kobashi, Koichiro Furuta, Masayuki Kurosaki, Beom Kyung K
    Journal of Gastroenterology and Hepatology.2025; 40(6): 1595.     CrossRef
  • Hepatitis B core-related antigen as a predictive biomarker for recurrence in primary hepatocellular carcinoma: A meta-analysis
    Ling-Bo Liang, Hai-Jun Zhang, Feng Liu, Qiao-Li Su
    World Journal of Gastrointestinal Oncology.2025;[Epub]     CrossRef
  • Construction and validation of a nomogram prediction model for antiviral efficacy based on clinical characteristics and intestinal microflora distribution in patients with chronic hepatitis B
    Hongjie Wu, Mingqiang Yue, Tianbao Wang, Xiaoxia Wei, Yanping Wang, Changyun Si
    Frontiers in Medicine.2025;[Epub]     CrossRef
  • Clinical outcomes after HBsAg clearance in chronic hepatitis B patients treated with Peg-IFN α: A study with an 11- to 173-month follow-up
    Wen Deng, Hongxiao Hao, Ziyu Zhang, Xinxin Li, Weihua Cao, Yaqin Zhang, Shiyu Wang, Zixuan Gao, Linmei Yao, Shuojie Wang, Xin Wei, Wei Yi, Linqing Zhao, Yao Xie, Minghui Li
    Virologica Sinica.2025; 40(4): 579.     CrossRef
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    Takehisa Watanabe, Katsuya Nagaoka
    Hepatology Research.2024; 54(3): 220.     CrossRef
  • Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy
    Ritsuzo Kozuka, Masaru Enomoto, Yoshimi Yukawa‐Muto, Naoshi Odagiri, Kohei Kotani, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Hideki Fujii, Sawako Uchida‐Kobayashi, Norifumi Kawada
    Hepatology Research.2024; 54(7): 615.     CrossRef
  • Long-Term Outcomes after Switching to Tenofovir Alafenamide in Patients with Chronic Hepatitis B
    Tomohiro Nishikawa, Masahiro Matsui, Saori Onishi, Kosuke Ushiro, Akira Asai, Soo-Ki Kim, Hiroki Nishikawa
    International Journal of Molecular Sciences.2024; 25(4): 2245.     CrossRef
  • Kinetics and Value of Hepatitis B Core-Related Antigen in Patients with Chronic Hepatitis B Virus Infection during Antiviral Treatment
    Lisa Sandmann, Birgit Bremer, Valerie Ohlendorf, Jerzy Jaroszewicz, Heiner Wedemeyer, Markus Cornberg, Benjamin Maasoumy
    Viruses.2024; 16(2): 255.     CrossRef
  • Identification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents
    Huijuan Song, Shangze Yang, Shuo Wu, Xiaoyu Qin, Ya Wang, Xican Ma, Jiaqi Gong, Meng Wei, Apeng Wang, Mengyuan Wang, Kun Lan, Juan Guo, Mingliang Liu, Xingjuan Chen, Yuhuan Li, Kai Lv
    European Journal of Medicinal Chemistry.2024; 268: 116280.     CrossRef
  • Quantitative Measurement of Serum HBcrAg Can Be Used to Assess the Feasibility of Safe Discontinuation of Antiviral Therapy for Chronic Hepatitis B
    Yong-Hong Wang, Hong Tang, En-Qiang Chen
    Viruses.2024; 16(4): 529.     CrossRef
  • Harnessing hepatitis B core-related antigen measurement to optimize posttreatment monitoring
    Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
    Clinical and Molecular Hepatology.2024; 30(2): 293.     CrossRef
  • Optimizing off-treatment outcome predictions: The potential of time-varying HBcrAg and the need for more research
    Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
    Clinical and Molecular Hepatology.2024; 30(2): 276.     CrossRef
  • Current perspectives of viral hepatitis
    Daisuke Usuda, Yuki Kaneoka, Rikuo Ono, Masashi Kato, Yuto Sugawara, Runa Shimizu, Tomotari Inami, Eri Nakajima, Shiho Tsuge, Riki Sakurai, Kenji Kawai, Shun Matsubara, Risa Tanaka, Makoto Suzuki, Shintaro Shimozawa, Yuta Hotchi, Ippei Osugi, Risa Katou,
    World Journal of Gastroenterology.2024; 30(18): 2402.     CrossRef
  • Two Concepts of Hepatitis B Core-Related Antigen Assay: A Highly Sensitive and Rapid Assay or an Effective Tool for Widespread Screening
    Takako Inoue, Shintaro Yagi, Yasuhito Tanaka
    Viruses.2024; 16(6): 848.     CrossRef
  • Novel biomarkers for chronic hepatitis B management
    Tai-Chung Tseng
    Clinical Liver Disease.2024;[Epub]     CrossRef
  • Role of circular RNAs in preeclampsia (Review)
    Hengxue Jiang, Tao Meng, Ziwei Li
    Experimental and Therapeutic Medicine.2024;[Epub]     CrossRef
  • Enhancing interventions for prevention of mother-to-child- transmission of hepatitis B virus
    Philippa C. Matthews, Ponsiano Ocama, Su Wang, Manal El-Sayed, Anna Turkova, Deborah Ford, Judith Torimiro, Ana Cristina Garcia Ferreira, Angélica Espinosa Miranda, Fernando Pio De La Hoz Restrepo, Emmanuel Seremba, Robinson Mbu, Calvin Q. Pan, Homie Raza
    JHEP Reports.2023; 5(8): 100777.     CrossRef
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  • 464 Download
  • 30 Web of Science
  • Crossref

Editorial

Viral hepatitis

Citations

Citations to this article as recorded by  Crossref logo
  • Unraveling Demographic Patterns in Hepatitis B Clinical and Laboratory Profiles: Insights From a Ghanaian Cohort: A Retrospective Study
    Napoleon Bellua Sam, Saeed Folorunsho Majeed, Adams Dramani
    Health Science Reports.2025;[Epub]     CrossRef
  • Gray zone and the need for expansion in chronic hepatitis B: From theory to clinical practice
    Thang Viet Luong, Ngoc Phan Hong Nguyen, Tri Van Nguyen, Duong Hung Tran, Thien Dinh Nguyen, Hai Nguyen Ngoc Dang
    World Journal of Hepatology.2025;[Epub]     CrossRef
  • Extrahepatic malignancies and antiviral drugs for chronic hepatitis B: A nationwide cohort study
    Moon Haeng Hur, Dong Hyeon Lee, Jeong-Hoon Lee, Mi-Sook Kim, Jeayeon Park, Hyunjae Shin, Sung Won Chung, Hee Jin Cho, Min Kyung Park, Heejoon Jang, Yun Bin Lee, Su Jong Yu, Sang Hyub Lee, Yong Jin Jung, Yoon Jun Kim, Jung-Hwan Yoon
    Clinical and Molecular Hepatology.2024; 30(3): 500.     CrossRef
  • The role of different viral biomarkers on the management of chronic hepatitis B
    Lung-Yi Mak, Rex Wan-Hin Hui, James Fung, Wai Kay Seto, Man-Fung Yuen
    Clinical and Molecular Hepatology.2023; 29(2): 263.     CrossRef
  • Diabetic MAFLD is associated with increased risk of hepatocellular carcinoma and mortality in chronic viral hepatitis patients
    Mi Na Kim, Kyungdo Han, Juhwan Yoo, Seong Gyu Hwang, Xuehong Zhang, Sang Hoon Ahn
    International Journal of Cancer.2023; 153(8): 1448.     CrossRef
  • 6,399 View
  • 198 Download
  • 7 Web of Science
  • Crossref

Review

RNA interference as a novel treatment strategy for chronic hepatitis B infection
Rex Wan-Hin Hui, Lung-Yi Mak, Wai-Kay Seto, Man-Fung Yuen
Clin Mol Hepatol 2022;28(3):408-424.
Published online February 17, 2022
DOI: https://doi.org/10.3350/cmh.2022.0012
Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. Functional cure of CHB, defined as sustainable hepatitis B surface antigen (HBsAg) seroclearance, is associated with improved clinical outcomes. However, functional cure is rarely attainable by current treatment modalities. RNA interference (RNAi) by small-interfering RNA (siRNA) and anti-sense oligonucleotide (ASO) has been studied as a novel treatment strategy for CHB. RNAi targets post-transcriptional messenger RNAs and pregenomic RNAs to reduce hepatitis B virus (HBV) antigen production and viral replication. By reducing viral antigens, host immune reconstitution against HBV may also be attained. Phase I/II trials on siRNAs have demonstrated them to be safe and well-tolerated. siRNA is effective when given in monthly doses with different total number of doses according to different trial design, and can lead to sustainable dose-dependent mean HBsAg reduction by 2–2.5 log. Incidences of HBsAg seroclearance after siRNA therapy have also been reported. ASOs have also been studied in early phase trials, and a phase Ib study using frequent dosing regimen within 4 weeks could achieve similar HBsAg reduction of 2 log from baseline. Given the established efficacy and safety of nucleos(t) ide analogues (NAs), future RNAi regimens will likely include NA backbone. While the current evidence on RNAi appears promising, it remains undetermined whether the potent HBsAg reduction by RNAi can result in a high rate of HBsAg seroclearance with durability. Data on RNAi from phase IIb/III trials are keenly anticipated.

Citations

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    Anita Bakrania, Yulin Mo, Gang Zheng, Mamatha Bhat
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    Rex Wan-Hin Hui, Lung-Yi Mak, Wai-Kay Seto, Man-Fung Yuen
    BioDrugs.2025; 39(1): 21.     CrossRef
  • Reply to: “ALT to qHBsAg ratio predicts HBsAg seroclearance in HBeAg-negative patients receiving Peg-IFNα based therapy”
    Rex Wan-Hin Hui, Lung-Yi Mak, Man-Fung Yuen
    Journal of Hepatology.2025; 82(5): e228.     CrossRef
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Editorial

Viral hepatitis

Elimination of hepatitis C: What would be the practical approach?
Hyung Joon Yim
Clin Mol Hepatol 2021;27(1):97-99.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0304

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Special topic: Alcoholic liver diseases
The 14th International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis (ISALPDC)

Long non-coding RNAs in liver diseases: Focusing on nonalcoholic fatty liver disease, alcohol-related liver disease, and cholestatic liver disease
Sen Han, Ting Zhang, Praveen Kusumanchi, Nazmul Huda, Yanchao Jiang, Zhihong Yang, Suthat Liangpunsakul
Clin Mol Hepatol 2020;26(4):705-714.
Published online October 1, 2020
DOI: https://doi.org/10.3350/cmh.2020.0166
Long non-coding RNAs (lncRNAs), a class of transcribed RNA molecules with the lengths exceeding 200 nucleotides, are not translated into protein. They can modulate protein-coding genes by controlling transcriptional and posttranscriptional processes. The dysregulation of lncRNAs has been related to various pathological disorders. In this review, we summarized the current knowledge of lncRNAs and their implications in the pathogenesis of three common liver diseases: nonalcoholic fatty liver disease, alcohol-related liver disease, and cholestatic liver disease. Future studies to further define the role of lncRNAs and their mechanisms in various types of liver diseases should be explored. An improved understanding from these studies will provide us a useful perspective leading to mechanism-based intervention by targeting specific lncRNAs for the treatment of liver diseases.

Citations

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  • LncRNA H19 promoted alcohol-associated liver disease through dysregulation of alternative splicing and methionine metabolism
    Zhihong Yang, Yanchao Jiang, Jing Ma, Li Wang, Sen Han, Nazmul Huda, Praveen Kusumanchi, Hui Gao, Themis Thoudam, Zhaoli Sun, Suthat Liangpunsakul
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    Yahui Wang, Gaurav Sanghvi, Suhas Ballal, RSK Sharma, Piyus Kumar Pathak, Aman Shankhyan, Jiaxuan Sun, Qingmin Chen, Yu Ma, Lei Huang, Yahui Liu
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    Ningning Chen, Yunxia Li, Xiaoying Li
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    Liz Simon, Kaitlin E. Couvillion, Meagan E. Donovan, Eden M. Gallegos, Flavia M. Souza‐Smith, Patricia E. Molina
    Comprehensive Physiology.2025;[Epub]     CrossRef
  • The Role of miRNA and Long Noncoding RNA in Cholestatic Liver Diseases
    Yudian Zhang, Ying Liu, Wen Huo, Longfei He, Bowen Li, Hui Wang, Fanyin Meng, Chenggang Duan, Bingru Zhou, Jinbo Wu, Rong Chen, Juan Xing, Ying Wan
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  • LncRNA taurine upregulated gene 1 in liver disease
    Zihao Fan, Hao Pan, Na Qu, Xin Wang, Lianrui Cao, Lijiang Chen, Mingxia Liu
    Clinica Chimica Acta.2024; 560: 119752.     CrossRef
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    Sina Kalantari Soltanieh, Sahar Khastar, Irwanjot Kaur, Abhishek Kumar, Jaya Bansal, Ata Fateh, Deepak Nathiya, Beneen Husseen, Mansour Rajabivahid, Mahmoud Dehghani-Ghorbi, Reza Akhavan-Sigari
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    Lu Liu, Sen Sun, Xiaohua Li
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  • The function of long non-coding RNA in non-alcoholic fatty liver disease
    Lianrui Cao, Na Qu, Xin Wang, Lijiang Chen, Mingxia Liu
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    Jinbang Huang, Mengtao Liu, Haiqing Chen, Jinhao Zhang, Xixi Xie, Lai Jiang, Shengke Zhang, Chenglu Jiang, Jieying Zhang, Qinhong Zhang, Guanhu Yang, Hao Chi, Gang Tian
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  • Transcriptomic Analysis Reveals the Messenger RNAs Responsible for the Progression of Alcoholic Cirrhosis
    Zhihong Yang, Sen Han, Ting Zhang, Praveen Kusumanchi, Nazmul Huda, Kelsey Tyler, Kristina Chandler, Nicholas J. Skill, Wanzhu Tu, Mu Shan, Yanchao Jiang, Jessica L. Maiers, Kristina Perez, Jing Ma, Suthat Liangpunsakul
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  • Research Progress on the Mechanism Between Polycystic Ovary Syndrome and Abnormal Endometrium
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Editorial

Hepatic neoplasm

Citations

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  • Micro-Nano Convergence-Driven Radiotheranostic Revolution in Hepatocellular Carcinoma
    Yisheng Peng, Hui Liu, Mengmeng Miao, Xu Cheng, Shangqing Chen, Kaifei Yan, Jing Mu, Hongwei Cheng, Gang Liu
    ACS Applied Materials & Interfaces.2025; 17(20): 29047.     CrossRef
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Review

Hepatic neoplasm

Recent advances in transarterial embolotherapies in the treatment of hepatocellular carcinoma
Edward Wolfgang Lee, Sarah Khan
Clin Mol Hepatol 2017;23(4):265-272.
Published online November 8, 2017
DOI: https://doi.org/10.3350/cmh.2017.0111
Management of hepatocellular carcinoma (HCC) can be maximized with the utilization of multiple treatment modalities including transplant, surgical resection and locoregional therapies including ablative therapies and transarterial embolotherapies. Although transplant and surgical resection offer the best clinical outcomes, a limited number of patients are amenable to these surgical treatment options due to the advanced disease at presentation. Transarterial embolotherapies including conventional transarterial chemoembolization (cTACE), bland transarterial embolization (TAE), drug-eluting beads transarterial chemoembolization (DEB-TACE) and selective internal radiation therapy (SIRT) with Yttrium 90 (90Y) have played an increasingly important role for these patients with unresectable HCC. With a better understanding of different transarterial embolotherapies, more personalized and precise treatment should be implemented for these patients with unresectable HCC. In this review, the updated evidence on the current role of each embolotherapy in the treatment of HCC is summarized.

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Original Articles

Viral hepatitis

Predictors of spontaneous viral clearance and outcomes of acute hepatitis C infection
Yoo-Kyung Cho, Young Nam Kim, Byung-Cheol Song
Clin Mol Hepatol 2014;20(4):368-375.
Published online December 24, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.4.368
Background/Aims

This study evaluated the predictors of spontaneous viral clearance (SVC), as defined by two consecutive undetectable hepatitis C virus (HCV) RNA tests performed ≥12 weeks apart, and the outcomes of acute hepatitis C (AHC) demonstrating SVC or treatment-induced viral clearance.

Methods

Thirty-two patients with AHC were followed for 12-16 weeks without administering antiviral therapy.

Results

HCV RNA was undetectable at least once in 14 of the 32 patients. SVC occurred in 12 patients (37.5%), among whom relapse occurred in 4. SVC was exhibited in 8 of the 11 patients exhibiting undetectable HCV RNA within 12 weeks. HCV RNA reappeared in three patients (including two patients with SVC) exhibiting undetectable HCV RNA after 12 weeks. SVC was more frequent in patients with low viremia than in those with high viremia (55.6% vs. 14.3%; P=0.02), and in patients with HCV genotype non-1b than in those with HCV genotype 1b (57.1% vs. 22.2%; P=0.04). SVC was more common in patients with a ≥2 log reduction of HCV RNA at 4 weeks than in those with a smaller reduction (90% vs. 9.1%, P<0.001). A sustained viral response was achieved in all patients (n=18) receiving antiviral therapy.

Conclusions

Baseline levels of HCV RNA and genotype non-1b were independent predictors for SVC. A ≥2 log reduction of HCV RNA at 4 weeks was a follow-up predictor for SVC. Undetectable HCV RNA occurring after 12 weeks was not sustained. All patients receiving antiviral therapy achieved a sustained viral response. Antiviral therapy should be initiated in patients with detectable HCV RNA at 12 weeks after the diagnosis.

Citations

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  • Elucidating the distinct contributions of miR-122 in the HCV life cycle reveals insights into virion assembly
    Marylin Rheault, Sophie E Cousineau, Danielle R Fox, Quinn H Abram, Selena M Sagan
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    Hang Zhang, Ahmed A. Quadeer, Matthew R. McKay
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    Magdalena Pluta, Maria Pokorska-Śpiewak, Małgorzata Aniszewska, Barbara Kowalik-Mikołajewska, Magdalena Marczyńska
    Klinische Pädiatrie.2021; 233(05): 211.     CrossRef
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    Alicja E. Grzegorzewska, Adrianna Mostowska, Monika K. Świderska, Wojciech Marcinkowski, Ireneusz Stolarek, Marek Figlerowicz, Paweł P. Jagodziński
    BMC Infectious Diseases.2021;[Epub]     CrossRef
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    Dorcas Ohui Owusu, Richard Phillips, Michael Owusu, Fred Stephen Sarfo, Margaret Frempong
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    Nina Leung, Seth E. Bernacki, Edward J. Bernacki
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Viral hepatitis

Multiplex polymerase chain reaction test for the diagnosis of acute viral hepatitis A
Nae-Yun Heo, Young-Suk Lim, Jihyun An, Sun-Young Ko, Heung-Bum Oh
Korean J Hepatol 2012;18(4):397-403.
Published online December 21, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.4.397
Background/Aims

The early diagnosis of acute hepatitis A (AHA) is hindered because serum IgM against hepatitis A virus (HAV) can yield false-negative results during the window period. This study evaluated the diagnostic accuracy of a polymerase chain reaction (PCR) kit for HAV RNA for the diagnosis of AHA.

Methods

Samples were collected from 136 patients with acute severe hepatitis at their admission to Asan Medical Center between June 2010 and July 2010. Samples were analyzed for serum IgM anti-HAV using an immunoassay test and for qualitative HAV RNA using the Magicplex HepaTrio PCR test kit. The diagnostic accuracies of these methods were tested on the basis of clinical and laboratory diagnoses of AHA.

Results

The concordance rate and kappa value between IgM anti-HAV and HAV RNA PCR were 88.2% and 0.707, respectively. For the diagnosis of AHA, the sensitivity and specificity of IgM anti-HAV were 90.7% and 100%, respectively, when an "equivocal" result was regarded as positive; and 79.1% and 100%, respectively, when an "equivocal" result was regarded as negative. The sensitivity and specificity of HAV RNA PCR were 81.4% and 100%, respectively. All four patients with negative IgM anti-HAV and positive HAV RNA PCR results and all four patients with equivocal IgM anti-HAV RNA and positive HAV RNA PCR results were eventually diagnosed with AHA.

Conclusions

The qualitative HAV RNA PCR test has an equivalent diagnostic accuracy for AHA compared to IgM anti-HAV and may be more sensitive during the window period.

Citations

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  • Hepatitis A Screening for Internationally Adopted Children From Hepatitis A Endemic Countries
    Vanessa N. Raabe, Casey Sautter, Mary Chesney, Judith K. Eckerle, Cynthia R. Howard, Chandy C. John
    Clinical Pediatrics.2014; 53(1): 31.     CrossRef
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Effects of the knockdown of hypoxia inducible factor-1α expression by adenovirus-mediated shRNA on angiogenesis and tumor growth in hepatocellular carcinoma cell lines
Sung Hoon Choi, Hye Won Shin, Jun Yong Park, Ji Young Yoo, Do Young Kim, Weon Sang Ro, Chae-Ok Yun, Kwang-Hyub Han
Korean J Hepatol 2010;16(3):280-287.
Published online September 30, 2010
DOI: https://doi.org/10.3350/kjhep.2010.16.3.280
Background/Aims

Hypoxia-inducible factor-1α (HIF-1α) is a central transcriptional factor involved in the cellular responses related to various aspects of cancer biology, including proliferation, survival, and angiogenesis, and the metabolism of the extracellular matrix in hypoxia. This study evaluated whether adenovirus-mediated small hairpin RNA (shRNA) against HIF-1α (shHIF-1α) inhibits cell proliferation and angiogenesis in hepatocellular carcinoma (HCC) cell lines.

Methods

Knockdown of HIF-1α expression was constructed by adenovirus-mediated RNA interference tools, and HCC cell lines infected with shHIF-1α coding virus were cultured under a hypoxia condition (1% O2) for 24 hours. Following infection, the expression levels of HIF-1α, angiogenesis factors, and matrix metalloproteinase (MMP) were examined using Western blotting. Cell proliferation and angiogenesis were measured by a cell proliferation assay (MTT assay) and an angiogenesis-related assay (invasion and tube-formation assay), respectively.

Results

Adenovirus mediated inhibition of HIF-1α induced suppression of tumor growth in HCC cell lines. It also down-regulated the expression of angiogenesis factor and MMP proteins. Angiogenesis as well as mobility of vascular cells to tumor was suppressed by adenovirus-mediated shHIF-1α-infected groups in human umbilical vein endothelial cells (HUVECs).

Conclusions

These data suggest that adenovirus-mediated inhibition of HIF-1α inhibits the invasion, tube formation, and cell growth in HUVECs and HCC cells.

Citations

Citations to this article as recorded by  Crossref logo
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    Sun-Mi Yoo, Cheol-Jung Lee, Hyun-Jung An, Joo Young Lee, Hye Suk Lee, Han Chang Kang, Sung-Jun Cho, Seung-Min Kim, Juhee Park, Dae Joon Kim, Yong-Yeon Cho
    International Journal of Molecular Sciences.2019; 20(8): 1994.     CrossRef
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    D Shneor, R Folberg, J Pe'er, A Honigman, S Frenkel
    Cancer Gene Therapy.2017; 24(2): 64.     CrossRef
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    Claire Viallard, Bruno Larrivée
    Angiogenesis.2017; 20(4): 409.     CrossRef
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    Joon Ho Lee, Wonhee Hur, Sung Woo Hong, Jung-Hee Kim, Sung Min Kim, Eun Byul Lee, Seung Kew Yoon
    Oncology Reports.2017; 37(2): 813.     CrossRef
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    ChengShi Chen, Rong Liu, JianHua Wang, ZhiPing Yan, Sheng Qian, Wei Zhang
    Cell Biochemistry and Biophysics.2015; 71(3): 1677.     CrossRef
  • Inhibition of tumour angiogenesis and growth by small hairpin HIF‐1α and IL‐8 in hepatocellular carcinoma
    Sung Hoon Choi, Oh‐Joon Kwon, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Seung Up Kim, Simon Weonsang Ro, Kyung Sik Kim, Jeon Han Park, Seungtaek Kim, Chae‐Ok Yun, Kwang‐Hyub Han
    Liver International.2014; 34(4): 632.     CrossRef
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    Dongjun Luo, Zhongxia Wang, Junyi Wu, Chunping Jiang, Junhua Wu
    BioMed Research International.2014; 2014: 1.     CrossRef
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    BIN WANG, YOU-MING DING, PING FAN, BING WANG, JUN-HUI XU, WEI-XING WANG
    Oncology Letters.2014; 8(2): 539.     CrossRef
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    Maulilio John Kipanyula, Paul Faustin Seke Etet, Lorella Vecchio, Mohammed Farahna, Elias Nchiwan Nukenine, Armel Hervé Nwabo Kamdje
    Cellular Signalling.2013; 25(2): 403.     CrossRef
  • The role of Aurora A in hypoxia-inducible factor 1α-promoting malignant phenotypes of hepatocelluar carcinoma
    Shi-Yun Cui, Jia-Yuan Huang, Yi-Tian Chen, Hai-Zhu Song, Gui-Chun Huang, Wei De, Rui Wang, Long-Bang Chen
    Cell Cycle.2013; 12(17): 2849.     CrossRef
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    Jin-Wook Kim
    The Korean Journal of Hepatology.2010; 16(3): 278.     CrossRef
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  • Crossref
The value of serum retinol-binding protein 4 Levels for determining disease severity in patients with chronic Liver disease
Jung Hyun Kwon, M.D., Seong Tae Park1, Gi Dae Kim, Ph.D.1, Chan Ran You, M.D., Jin Dong Kim, M.D., Hyun Young Woo, M.D., Jeong Won Jang, M.D.1, Chang Wook Kim, M.D., Si Hyun Bae, M.D., Jong Young Choi, M.D., Seung Kew Yoon, M.D.
Korean J Hepatol 2009;15(1):59-69.
Published online March 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.1.59
Backgrounds/Aims
Serum retinol-binding protein 4 (RBP4) is known to be a specific transport protein for retinol, and has recently been reported to be associated with insulin resistance. Hyaluronic acid (HA) is a well-known marker of liver fibrosis. In this study, the degree to which serum RBP4 levels can be used to predict disease severity in patients with chronic liver disease (CLD) was evaluated. Methods: Serum levels of RBP4 and HA were measured in 573 CLD patients [235 with chronic hepatitis (CH), 230 with liver cirrhosis Child-Pugh grade (Child) A, and 108 with liver cirrhosis with Child B and C] and 40 normal controls. Results: The mean age of the whole cohort was 53.1 years and the causes of CLD were hepatitis B virus (61.9%), hepatitis C virus (9.8%), alcohol (9.0%), and nonalcoholic steatohepatitis (3.8%). Serum levels of RBP4 significantly reduced and HA increased with disease condition, from none (normal controls) to advanced cirrhosis (normal control: RBP4 4.3±0.1 mg/dL, HA 25.3±28.1 ng/mL; CH: RBP4 3.6±0.1 mg/dL, HA 75.5±7.8 ng/mL; cirrhosis with Child A: RBP4 2.6±0.1 mg/dL, HA 184.4±14.5 ng/mL; and cirrhosis with Child B and C: RBP4 1.6±0.1 mg/dL, HA 656.5±86.7 ng/mL; P<0.001, respectively). Serum RBP4 level was a distinguishing factor at the early stage of CLD between CH and Child A cirrhosis (post-hoc test; P<0.001) and was correlated with histological fibrosis score (n=80, P<0.05) and several biochemical factors. Antiviral therapy (n=45, median interval 1,205 days) resulted in an improvement in serum RBP4 levels (P=0.001). Conclusions: The results of our study suggest that RBP4 is a serologic marker for disease severity in patients with CLD. It could also be useful as an early marker of CLD and of the relative success of antiviral therapy. (Korean J Hepatol 2008;15:59-69)

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Inhibition of in vitro hepatitis B virus replication by Lentivirus-mediated short-hairpin RNA against HBx
Jin Wook Kim , Sang Hyub Lee , Young Soo Park , Sook Hyang Jeong , Na Young Kim , Dong Ho Lee
Korean J Hepatol 2009;15(1):15-24.
Published online March 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.1.15
Backgrounds/Aims
Hepatitis B virus (HBV) replicates via RNA intermediates, which could serve as targets for RNA interference (RNAi). Vector-mediated short-hairpin RNA (shRNA) can induce sustained RNAi in comparison to small interfering RNA. Lentiviral vector is known to induce prolonged RNAi with high transduction efficiency. In this study, we sought to test the in vitro efficacy of shRNA delivered by a lentiviral vector in suppressing the replication of HBV. Methods: Two shRNA sequences against the hepatitis B viral protein HBx (sh1580 and sh1685) were cloned downstream of the U6 promoter in an HIV-based plasmid to generate third-generation lentiviral vectors. HepAD38 cells were transduced with anti-HBx lentiviral vectors, and HBV replication was induced for 5 days. HBV DNA was isolated and quantified using real-time PCR. Results: Lentiviral vectors encoding the shRNA against HBV transduced HepAD38 cells with high efficacy. The total intracellular HBV DNA content was significantly reduced by both sh1580 and sh1685 (2.9% and 12.0%, respectively; P<0.05). HBV covalently closed circular DNA (cccDNA) was also suppressed significantly (19.7% and 25.5%, respectively; P<0.05). Conclusions: Lentivirus-mediated delivery of shRNA against HBx can effectively suppress the replication of HBV and reduce HBV cccDNA in cell culture systems. (Korean J Hepatol 2008;15:15-24)

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Editorial

Inhibition of hepatitis B virus replication by RNA interference
Yun Gyu Park
Korean J Hepatol 2009;15(1):1-6.
Published online March 31, 2009
DOI: https://doi.org/10.3350/kjhep.2009.15.1.1
  • 5,554 View
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Original Articles

Factors Predictive of Response to Interferon Therapy in Chronic HCV Infection
Yun Soo Kim , So Young Kwan , Dong Jin Suh , Chang Hong Lee
Korean J Hepatol 1996;2(2):176-185.
Backgound/Aim '. Although interferon-a(IFNa) is currently the most effective antiviral agent for treating patients with chronic hepatitis C, its efficacy is not always reliable. Factors suggested to infruence outcome of IFN-a therapy for chronic hepatitis C are histological activity, level of viremia and HCV genotype, etc. The aim of this study was to determine the relationship between several pretreatment factors and response to IFN-a therapy in patients with chronic HCV infection. Methods .' Fifty-four patients with chronic HCV infection(47 with chronic hepatitis and 7 with liver cirrhosis) who received IFN-a(2a or 2b) therapy(3 6 MU, three times a week, for 3 12 months) were included. Level of serum HCV RNA(50 patients), HCV genotype(27 patients) and IgM anti- HCV(21 patients) during pretreatment period were assayed. Results '. Overall, 19(35%) subjects achieved sustained response(SR), 12(22%) had transient response(TR) and 23(43%) did not respond (nonresponse;NR). Mean age of patients with SR, TR and NR was 46+ 10, 51+ 7.5 and 54+ 9.7 years, respectively(p<0.05 between SR and NR). Among 30 patients with biopsy-proven chronic hepatitis, 13(43%) achieved SR;but only one(14%) in 7 patients with liver cirrhosis. Mean serum HCV RNA level(X10' copies/ml) was higher in nonresponders(7,7+ 13.0) compared with SR(2.3+ 2. 7) or TR(3.1+ 4.9), although statistically insignificant HCV genotyping in 27 patients revealed type la in 5(18.5%), 1b in 14(52%), 2a in 5(18.5%), 2b in 1(3.7%) and 4 in 2(7%), respectively. In non-1b patients, SR rate was significantly higher than 1b patients(69.2% vs. 21.4%, p=0.03). Although IgM anti-HCV was positive in 12(57%) among 21 patients studied, the positive rate and the titer of IgM anti-HCV was not significantly different in three groups. Condusion '. Our results suggest that in patients with chronic hepatitis C, infection with genotype 1b, old age, high serum HCV RNA level and the presence of cirrhosis would predict poor response to IFN therapy.
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The Detection of Hepatitis G Virus RNA by RT - PCR in Various Liver Diseases
Kwang Hyub Han , Won Choi , Young Nyun Park , Young Woong Hwang , Wang Sik Ryu , Eun Sin Park , Kwan Sik Lee , Chae Yoon Chon , Young Myoung Moon , Chan Il Park
Korean J Hepatol 1997;3(2):123-132.
Background/Aims
Recently, nucleotide sequences from a novel virus, termed hepatitis G virus (HGV), were identified in serum from a patient with cryptogenic hepatitis and suggested as agent of non A-E hepatitis. HGV has been isolated from patients with various liver diseases but clinical implications of this new agent remain largely unresolved. In Korea, the etiology of substantial fraction of hepatitis has remained undefined and there has been no report concerning HGV. Methods: To determine the infection rate of HGV, RT-PCR of 5 UTR of HGV was performed, and to understand the clinical implication of HGV, medical records of 115 patients with various liver diseases were reviewed. Of 115 patients, 63 were male and 52 were female. Their mean age was 44 years (19-74) and their mean AST and ALT were 121.3+278.7 IU/L and 172.2+253.3 IU/L, respectively. Of 115 patients, 58 (50.4%) had no specific cause of liver diseases, 37 (32.2%) were infected with hepatitis B and/or C virus and 20 (17.4%) had non-viral identifiable liver diseases. Results: 1. HGV RNA was detected in 15 (13.0%) patients of 115 patients. 2, Among the 15 HGV RNA positive cases, 7 were male and 8 were female. Their mean age was 48 years (19-72) and their mean AST and ALT were 71.9+45.2 IU/L, 97.4+66.8 IU/I respectively. 3. HGV RNA was detected in 8(13.8%) of 58 patients without obvious causes of their liver diseases and in 7 (18.9%) of 37 patients infected with HBV and/or HCV. However, HGV RNA was not detected fram 20 patients with non-viral liver diseases such as alcoholic liver diseases, autoimmune hepatitis, PBC, or fatty liver. 4. HGV RNA was detected in 5 (19.2%) of 26 patients with acute hep- atitis, in 6 (9.4%) of 64 patients with chronic hepatitis, in 1 (14.3%) of 7 patients with liver cirrhasis, and iB 3 (27.3%) Of 11 pafients with hepatocellular caIcinoma. 5. These was no slatistically significant difference in sex, age, history of transfusion, serum ALT level, etiologies and status of liver diseases between HGV RNA positve and negative group. Conclusions: the prevalence of HGV infection is quite high among the patients who have no specific cause of acute or chronic liver diseases and HGV can be coinfected with HBV and/ar HCV infection in Korea.
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Prevalence of Hepatitis G Virus Infection in Patients with Chronic Renal Failure
Woo-Won Shin, M.D., Kyung-Ha Song, M.D., Jeong-Hwan Cho, M.D., Hyun-Sook Ahn*, Sung-Wook Lee, M.D., Dong-Joo Keum, M.D., Sung-Jin Bae, M.D.†, Sun-Taec Kim, M.D.†, Kwang-Yul Chang, M.D., Jung-Ha Park, M.D., Myung-Hwan Noh, M.D., Seong-Eun Kim, M.D., Sang-Young Han, M.D., Seok-Reyol Choi, M.D., and Ki-Hyun Kim, M.D.
Korean J Hepatol 2000;6(1):82-90.
Backgrounds/Aims
: To investigate the prevalence and clinical implications of hepatitis G virus (HGV) infection in patients with chronic renal failure, a cross-sectional study of 131 hemodialysis patients and 33 kidney transplantation recipients was conducted. Methods : HGV RNA was amplified by reverse-transcription (RT) polymerase chain reaction (PCR) assay with primers from the 5'-untranslated region of the viral genome. Results : The prevalence of HGV infection in patients with chronic renal failure was 25%(41/164). The following factors were taken into consideration: the mean age(43.15±11.97 years vs 46.46±13.08 years), the male to female ratio(2.15:1 vs 1.86:1), the mean of the dialysis duration(4.58±3.18 years vs 3.90±3.31 years), transfusion history (75.6% vs 62.6%), the mean of the ALT level during the prior 6 months(25.78±21.50 IU/L vs 23.00±59.49 IU/L), and the amount of transfusion(6.22±8.03 units vs 5.74±9.44 units). The anti-HCV(4.88% vs 8.94%) showed no difference between HGV RNA positive and negative group. The HBsAg positive ratio was 19.5% and 5.81% in HGV RNA positive group and negative group, respectively. Conclusion : The prevalence of HGV infection in patients with chronic renal failure was 25%. There was a higher rate of HBsAg positivity in the HGV RNA positive group rather than in the negative group. HGV infection did not seem to be associated with clinically significant hepatitis.(Korean J Hepatol 2000;6:82-90)
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Quantitation of Hepatitis C Virus RNA by Competitive RT-PCR and DNA-ELISA Method
Kang Seok Seo, M.D., Seung Jung Kee1, M.D., Soon Pal Suh1, M.D., Sei Jong Kim, M.D.
Korean J Hepatol 2000;6(2):156-171.
Background/Aims
Quantitation of Hepatitis C Virus (HCV) RNA in serum is important for monitoring the response to interferon-α therapy in patients with chronic hepatitis C. Several commercial assays are recently available, but they are expensive and cannot be used as a gold standard. Methods: An in-house competitive reverse transcription-polymerase chain reaction (cRT-PCR) was developed and validated. The procedure involves the construction of a mutant and wild type HCV RNA internal standard (IS), cRT-PCR, and colorimetric detection with DNA-ELISA. A standard curve was obtained and used for final HCV RNA quantitation. Results: The standard curve was linear over the range of 1×104 to 5×107 copies/mL of the HCV RNA standard (r=0.976). This in-house cRT-PCR was comparable with the branched DNA (bDNA) assay (Quantiplex HCV 2.0, Chiron, USA) with positive correlation between the two tests (r=0.735). Conclusion: The quantitation of HCV RNA by in-house cRT-PCR and DNA ELISA was more sensitive and had wider range of detection compared to bDNA assay. This assay is useful for follow-up of HCV RNA concentration after interferon-α therapy.(Korean J Hepatol 2000;6:156-171)
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Cyber Hepatology

It is our great pleasure to announce that the Taehan Kan Hakhoe Chi (The Korean Journal of Hepatology) was approved for listing, from 2002, in the Index Medicus, Medline/PubMed of the National Library of Medicine, NIH of USA. Herein, I review the searching tools employing a Medical Subject Heading (MeSH) such as liver disease and liver neoplasm or an author index for this Journal in the PubMed at a website. Of course, The Korean Journal of Hepatology should be continually striving to be upgraded. Dream comes true.(Korean J Hepatol 2003; 9:35-41)
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Original Article
Clinical Significance of Intrahepatic HCV RNA Level in Chronic HCV Infection
Jae Young Jang, M.D., Yun Soo Kim, M.D.2, Sang Gyune Kim, M.D., Young Seok Kim, M.D., Young Deok Cho, M.D., Joon Sung Lee, M.D., So Young Jin, M.D.1, Moon Sung Lee, M.D., Ju Hyun Kim, M.D.2, Chan Sup Shim, M.D., and Boo Sung Kim, M.D.
Korean J Hepatol 2006;12(4):515-523.
Background/Aims
This study was carried out to identify the correlation between the serum HCV RNA and the liver HCV RNA level in chronic hepatitis C patients and to evaluate the differences of biochemistry, histology, HCV genotype and their response to antiviral therapy according to intrahepatic HCV RNA levels. Methods: For thirty-six chronic hepatitis C patients (M:F=22:14, CH:LC=27:9), percutaneous liver biopsy was performed, and serum and liver HCV RNA level were measured. Seventeen patients were treated with IFN-α and ribavirin. Results: There was a significant correlation between intrahepatic and serum HCV RNA levels (intrahepatic HCV RNA: 1.9±3.1×107 copies/g vs. serum HCV RNA: 3.2±3.2×106 copies/mL)(r=0.538, P<0.01). Total histological activity score (r=0.346, P=0.04) and periportal inflammation (r=0.398, P=0.01) were correlated with intrahepatic HCV RNA level. However, serum HCV RNA level was not correlated with histological activity. Serum ALT was not correlated with intrahepatic HCV RNA level. Intrahepatic HCV RNA level was higher in genotype 1 than genotype 2 or 3 (P=0.07). Intrahepatic HCV RNA level was not correlated with response to anti-viral therapy. Conclusion: Intrahepatic HCV RNA level was correlated with serum HCV RNA level and periportal inflammation in patients with chronic hepatitis C. It seems that intrahepatic HCV RNA level is more closely related to histological features than serum HCV RNA level. (Korean J Hepatol 2006;12:515-523)
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