Clinical and Molecular Hepatology

"Myeong Jun Song"

Original Articles

DNMT1 Facilitates the Progression of MASLD by Impeding Transcription Mediated by HNF4α and PPARα: Hyun Ahm Sohn, Hanyong Go, Tae Hyeon An, Jun Min Lee, Hee-Jin Kim, Keeok Haam, Amal Magdy, Hyo-Jung Jung, Yang-Ji Shin, Hyun Jung Lim, Yujin Jeong, Yejin Bae, Youngae Jung, Seong-Hwan Park, Kyung Chan Park, Myeong Jun Song, Eun-Wie Cho, Eun-Soo Kwon, Jeong Hwan Park, Murim Choi, Geum-Sook Hwang, Dong Hyeon Lee, Stefano Romeo, Kyoung-Jin Oh, Won Kim, Mirang Kim; Received September 25, 2025 Accepted January 23, 2026 Published online January 27, 2026; DOI: https://doi.org/10.3350/cmh.2025.1099 [Accepted]

Abstract
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Background/Aims
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. Aberrant DNA methylation, which is primarily maintained by DNA methyltransferase 1 (DNMT1), has been linked to metabolic dysregulation; however, its contribution to MASLD pathogenesis remains poorly defined. This study aimed to elucidate the role of DNMT1-mediated methylation in transcriptional regulation during MASLD progression and to determine whether DNMT1 inhibition can reverse disease-associated epigenetic and transcriptional alterations.
Methods
We conducted integrated analyses of the liver transcriptome (n = 131) and DNA methylome (n = 106) of patients with biopsy-proven MASLD. We evaluated the effect of DNMT1 inhibition with 5-aza-4′-thio-2′-deoxycytidine (Aza-TdC) on a diet-induced MASLD mouse model. Multiomics approaches, including DNA methylome profiling, lipidomics, bulk and single-nucleus RNA sequencing, and chromatin immunoprecipitation sequencing, were applied to elucidate the role of DNMT1-mediated DNA methylation in regulating pathogenic gene expression.
Results
DNA methylome profiling revealed increased methylation variability associated with increased DNMT1 expression in MASLD patients. DNMT1 inhibition ameliorated dysregulated lipid metabolism by reducing hepatic triacylglycerol accumulation and inflammation. Aza-TdC treatment partially reversed MASLD-related hypermethylation of hepatocyte nuclear factor 4 alpha (HNF4α)- and peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes, restoring their transcriptional activity. Notably, Aza-TdC reactivated the gluconeogenic enzyme-encoding gene phosphoenolpyruvate carboxykinase 1 (PCK1), which was hypermethylated and transcriptionally repressed in MASLD. Targeted DNA methylation of the PCK1 promoter using CRISPRoff confirmed the direct epigenetic regulation of PCK1 expression.
Conclusions
Targeting DNMT1 may mitigate lipid dysregulation and inflammation by reversing hypermethylation and restoring HNF4α- and PPARα-dependent gene transcription, highlighting DNMT1 as a potential therapeutic target for MASLD.

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Liver fibrosis, cirrhosis, and portal hypertension

Cardiac diastolic dysfunction predicts poor prognosis in patients with decompensated liver cirrhosis: Soon Kyu Lee, Myeong Jun Song, Seok Hwan Kim, Hyo Jun Ahn; Clin Mol Hepatol 2018;24(4):409-416.
Published online August 27, 2018; DOI: https://doi.org/10.3350/cmh.2018.0034

Abstract
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Background/Aims
Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cardiac dysfunction in patients with liver cirrhosis (LC). However, the effect of LVDD on survival has not been clarified, especially in decompensated LC.
Methods
We prospectively enrolled 70 patients with decompensated LC, including ascites or variceal bleeding, at Daejeon St. Mary’s Hospital from April 2013 to April 2015. The cardiac function of these patients was evaluated using 2D echocardiography with tissue Doppler imaging. The diagnosis of LVDD was based on the American Society of Echocardiography guidelines. The primary endpoint was overall survival.
Results
Forty-four patients (62.9%) had LVDD. During follow-up (22.3 months), 18 patients died (16 with LVDD and 2 without LVDD). The survival rate was significantly lower in patients with LVDD than in those without LVDD (31.1 months vs. 42.6 months, P=0.01). In a multivariate analysis, the Child-Pugh score and LVDD were independent predictors of survival. Moreover, patients with a ratio of early filling velocity to early diastolic mitral annular velocity (E/e’) ≥ 10 (LVDD grade 2) had lower survival than patients with E/e’ ratio < 10.
Conclusions
The presence of LVDD is associated with poor survival in patients with decompensated LC. Therefore, it may be important to monitor and closely follow LVDD patients.

Citations

Citations to this article as recorded by

What’s new in critical illness and injury science? Cardiac dysfunction in patients with cirrhosis and its correlation with Child - Turcott - Pugh (CTP) SCORE
Tarun Sharma, Christopher Caspers
International Journal of Critical Illness and Injury Science.2025; 15(3): 99. CrossRef
Cirrhotic cardiomyopathy: a systematic review and meta-analysis of prevalence across various diagnostic approaches
Mohammed Ewid, Suliman Alsagaby, Abdulsalam Al-Ruqi, Odi Al-Shamikh, Abdulelah Aljohani, Mariam Safwan Bourgleh, Moaz Safwana
Annals of Saudi Medicine.2025; 45(4): 270. CrossRef
International Liver Transplantation Society/Liver Intensive Care Group of Europe guidelines for cardiovascular assessment before liver transplantation
Emmanuel Weiss, Gonzalo Crespo, Alexandra Anderson, Gianni Biancofiore, Ryan Chadha, Jacek B. Cywinski, Andrea De Gasperi, James Findlay, Marc Giménez-Milà, Constantine Karvellas, Michael Kaufman, Ashish Malik, Marina Moguilevitch, Sher-Lu Pai, Koen Reynt
American Journal of Transplantation.2025;[Epub] CrossRef
Left Ventricular Diastolic Dysfunction Increases the Risk of Medium-term Mortality in Patients with Cirrhotic Ascites
Sheng-Hao Li, Lu Zhang, Hong-Juan Li, Ye Li, Yan-Min Zheng, Qing-Qing Wang
Romanian Journal of Internal Medicine.2025;[Epub] CrossRef
Association of NT-proBNP and sST2 with Diastolic Dysfunction in Cirrhotic Patients and Its Therapeutic Implications
Roxana Mihaela Chiorescu, Alexandru Ruda, Romeo Chira, Georgiana Nagy, Adriana Bințințan, Ștefan Chiorescu, Mihaela Mocan
International Journal of Molecular Sciences.2025; 27(1): 261. CrossRef
Association of echocardiography-related parameters with the prognosis of decompensated cirrhosis: a retrospective cohort study
Weiwei Wang, Liyan Dong, Yue Gao, Fangbo Gao, Zhongchao Wang, Min Ding, Chunru Gu, Zhe Li, Yue Yin, Menghua Zhu, Hongxin Chen, Hongyu Li, Xingshun Qi
Current Medical Research and Opinion.2024; 40(4): 613. CrossRef
An Overview of the Clinical Implications of Cirrhotic Cardiomyopathy
Sarah Myers, Pakinam Mekki, Manhal Izzy
Current Hepatology Reports.2024; 23(3): 389. CrossRef
Association of left ventricular diastolic dysfunction with inflammatory activity, renal dysfunction, and liver-related mortality in patients with cirrhosis and ascites
Georgios Kalambokis, Maria Christaki, Ilias Tsiakas, Grigorios Despotis, Lampros Lakkas, Spiridon Tsiouris, Xanthi Xourgia, Georgios S. Markopoulos, Lefkothea Dova, Haralampos Milionis
European Journal of Gastroenterology & Hepatology.2024; 36(6): 775. CrossRef
H2FPEF Scores Are Increased in Patients with NASH Cirrhosis and Are Associated with Post-liver Transplant Heart Failure
David G. Koch, Don C. Rockey, Sheldon S. Litwin, Ryan J. Tedford
Digestive Diseases and Sciences.2024; 69(8): 3061. CrossRef
Systolic and diastolic impairment in cirrhotic cardiomyopathy: insights from a cross-sectional study
Hala Mansoor, Mahnam Khizer, Aneela Afreen, Noor Masood Sadiq, Aamir Habib, Shafqat Ali, Asim Raza, Tayyaba Hafeez
Egyptian Liver Journal.2024;[Epub] CrossRef
Cirrhotic cardiomyopathy – negative prognosis factor in cirrhosis
Andreea Maria Marin, Ovidiu Calapod, Gabriela Anca Angelescu, Corina Costache, Ruxandra Sfeatcu, Tribus Laura Carina
Medic.ro.2023; 2(152): 19. CrossRef
Left Ventricular Diastolic Dysfunction Defined Using the 2016 ASE Criteria and Mortality after a Liver Transplant in Patients with End-Stage Liver Disease: A Systematic Review
Carlos E. González-Martínez, Diego Regalado-Ceballos, Samantha Medrano-Juárez, Airam Regalado-Ceballos, Isaí E. Hernández-Padilla, José R. Azpiri-López, Homero Nañez-Terreros, Linda E. Muñoz-Espinosa
Gastroenterology Insights.2023; 14(4): 653. CrossRef
Is Cirrhotic Cardiomyopathy Related to Cirrhosis Severity?
Subhash Chandra Dash, Beeravelli Rajesh, Suresh Kumar Behera, Naba Kishore Sundaray, Praveen Patil
Rambam Maimonides Medical Journal.2023; 14(1): e0001. CrossRef
Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications
Csaba Matyas, György Haskó, Lucas Liaudet, Eszter Trojnar, Pal Pacher
Nature Reviews Cardiology.2021; 18(2): 117. CrossRef
The prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria
Marcel Razpotnik, Simona Bota, Philipp Wimmer, Michael Hackl, Gerald Lesnik, Hannes Alber, Markus Peck‐Radosavljevic, Virginia Hernandez‐Gea
Liver International.2021; 41(5): 1058. CrossRef
Direct Bilirubin Is More Valuable than Total Bilirubin for Predicting Prognosis in Patients with Liver Cirrhosis
Han Ah Lee, Joon Young Jung, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyonggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Kwan Soo Byun, Soon Ho Um, Yeon Seok Seo
Gut and Liver.2021; 15(4): 599. CrossRef
Current Concepts of Cirrhotic Cardiomyopathy
Manhal J. Izzy, Lisa B. VanWagner
Clinics in Liver Disease.2021; 25(2): 471. CrossRef
Diastolic Dysfunction Is a Predictor of Poor Survival in Patients with Decompensated Cirrhosis
Manas Kumar Behera, Surendra Nath Swain, Manoj Kumar Sahu, Gaurav Kumar Behera, Debakanta Mishra, Jimmy Narayan, Ayaskant Singh, Shobhit Agarwal, Pradeep Kumar Mallick, Fredric D. Gordon
International Journal of Hepatology.2021; 2021: 1. CrossRef
Factors Predicting Cardiac Dysfunction in Patients with Liver Cirrhosis
Manas Kumar Behera, Jimmy Narayan, Manoj Kumar Sahu, Suresh Kumar Behera, Ayaskanta Singh, Debakanta Mishra, Shobhit Agarwal, Kanishka Uthansingh
Middle East Journal of Digestive Diseases.2021; 13(3): 216. CrossRef
Impact of the 2016 ASE/EACVI Guidelines on diastolic function reporting in routine clinical practice
Prabhakaran Gopalakrishnan, Robert Biederman
Echocardiography.2020; 37(4): 546. CrossRef
Early echocardiographic signs of diastolic dysfunction predict acute kidney injury in cirrhotic patients
Pei-Shan Wu, Ying-Wen Wang, Cheng-Chun Tai, Yun-Cheng Hsieh, Pei-Chang Lee, Chin-Chou Huang, Yi-Hsiang Huang, Ming-Chih Hou, Han-Chieh Lin, Kuei-Chuan Lee
Journal of the Chinese Medical Association.2020; 83(11): 984. CrossRef
An update on cirrhotic cardiomyopathy
Søren Møller, Karen V. Danielsen, Signe Wiese, Jens D. Hove, Flemming Bendtsen
Expert Review of Gastroenterology & Hepatology.2019; 13(5): 497. CrossRef
Liver cirrhosis and left ventricle diastolic dysfunction: Systematic review
Ieva Stundiene, Julija Sarnelyte, Ausma Norkute, Sigita Aidietiene, Valentina Liakina, Laura Masalaite, Jonas Valantinas
World Journal of Gastroenterology.2019; 25(32): 4779. CrossRef
Syndecan-1: A Review on Its Role in Heart Failure and Chronic Liver Disease Patients’ Assessment
Radu-Stefan Miftode, Ionela-Lăcrămioara Şerban, Amalia-Stefana Timpau, Ionela-Larisa Miftode, Adriana Ion, Ana-Maria Buburuz, Alexandru-Dan Costache, Irina-Iuliana Costache
Cardiology Research and Practice.2019; 2019: 1. CrossRef
Cirrhotic cardiomyopathy: An independent prognostic factor for cirrhotic patients
Yun Bin Lee, Jeong-Hoon Lee
Clinical and Molecular Hepatology.2018; 24(4): 372. CrossRef

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Viral hepatitis

Efficacy and safety of sofosbuvir plus ribavirin for Korean patients with hepatitis C virus genotype 2 infection: A retrospective multi-institutional study: Young Min Kim, Suk Bae Kim, Il Han Song, Sae Hwan Lee, Hong Soo Kim, Tae Hee Lee, Young Woo Kang, Seok Hyun Kim, Byung Seok Lee, Hee Bok Chae, Myeong Jun Song, Ji Woong Jang, Soon Young Ko, Jae Dong Lee; Clin Mol Hepatol 2018;24(3):311-318.
Published online June 4, 2018; DOI: https://doi.org/10.3350/cmh.2017.0070

Abstract
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Background/Aims
Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection.
Methods
We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area.
Results
A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27–96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients.
Conclusions
A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.

Citations

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Combination treatment with sofosbuvir and ribavirin for patients diagnosed with hepatitis C genotype 2: A real-world, single-center study
Ik Sung Choi, Kwang Min Kim, Sang Goon Shim
Arab Journal of Gastroenterology.2021; 22(1): 23. CrossRef
Real-Life Effectiveness and Safety of Glecaprevir/Pibrentasvir for Korean Patients with Chronic Hepatitis C at a Single Institution
Young Joo Park, Hyun Young Woo, Jeong Heo, Sang Gyu Park, Young Mi Hong, Ki Tae Yoon, Dong Uk Kim, Gwang Ha Kim, Hyung Hoi Kim, Geun Am Song, Mong Cho
Gut and Liver.2021; 15(3): 440. CrossRef
Sofosbuvir‐based therapies in genotype 2 hepatitis C virus cirrhosis: A real‐life experience with focus on ribavirin dose
Carlo Smirne, Antonio D'Avolio, Mattia Bellan, Alessandro Gualerzi, Maria G. Crobu, Mario Pirisi
Pharmacology Research & Perspectives.2021;[Epub] CrossRef
Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment
Jennifer J. Lin, Catrina M. Loucks, Jessica N. Trueman, Britt I. Drögemöller, Galen E.B. Wright, Eric M. Yoshida, Jo-Ann Ford, Samuel S. Lee, Richard B. Kim, Bandar Al-Judaibi, Ute I. Schwarz, Alnoor Ramji, Edward Tam, Colin J. Ross, Bruce C. Carleton
Biomedicine & Pharmacotherapy.2021; 143: 112195. CrossRef
Incidence, risk factors and impact on virological response of anemia in chronic genotype 2 hepatitis C receiving sofosbuvir plus ribavirin
Chi-Ching Chen, Shui-Yi Tung, Kuo-Liang Wei, Chien-Heng Shen, Te-Sheng Chang, Wei-Ming Chen, Huang-Wei Xu, Chih-Wei Yen, Yi-Hsing Chen, Sheng-Nan Lu, Chao-Hung Hung
Journal of the Formosan Medical Association.2020; 119(1): 532. CrossRef
Hepatocellular Carcinoma Risk According to Regimens for Eradication of Hepatitis C Virus; Interferon or Direct Acting Antivirals
Hye Won Lee, Dai Hoon Han, Hye Jung Shin, Jae Seung Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Beom Kyung Kim
Cancers.2020; 12(11): 3414. CrossRef
Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose
Eun Sun Jang, Kyung-Ah Kim, Young Seok Kim, In Hee Kim, Byung Seok Lee, Youn Jae Lee, Woo Jin Chung, Sook-Hyang Jeong
Gut and Liver.2020; 14(6): 775. CrossRef
Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium
Chung-Feng Huang, Etsuko Iio, Dae Won Jun, Eiichi Ogawa, Hidenori Toyoda, Yao-Chun Hsu, Hiroaki Haga, Shinji Iwane, Masaru Enomoto, Dong Hyun Lee, Grace Wong, Chen-Hua Liu, Toshifumi Tada, Wan-Long Chuang, Ramsey Cheung, Jun Hayashi, Cheng-Hao Tseng, Sato
Hepatology International.2019; 13(5): 587. CrossRef
Comparison of the Clinical Characteristics and Outcomes between Leprosy-Affected Persons in Sorokdo and the General Population Affected by Chronic Hepatitis C in Korea
Young-Hwan Ahn, Hyungcheol Park, Myeon Jae Lee, Dong Hyun Kim, Sung Bum Cho, Eunae Cho, Chung Hwan Jun, Sung Kyu Choi
Gut and Liver.2019; 13(5): 549. CrossRef
Does the old-fashioned sofosbuvir plus ribavirin treatment in genotype 2 chronic hepatitis C patients still works for Koreans?
Jong Eun Yeon
Clinical and Molecular Hepatology.2018; 24(3): 294. CrossRef
Ribavirin/sofosbuvir

Reactions Weekly.2018; 1727(1): 247. CrossRef

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Hepatic neoplasm

A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function: Hyun Yang, Hyun Young Woo, Soon Kyu Lee, Ji Won Han, Bohyun Jang, Hee Chul Nam, Hae Lim Lee, Sung Won Lee, Do Seon Song, Myeong Jun Song, Jung Suk Oh, Ho Jong Chun, Jeong Won Jang, Angelo Lozada, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon; Clin Mol Hepatol 2017;23(2):128-137.
Published online May 10, 2017; DOI: https://doi.org/10.3350/cmh.2016.0071

Background/Aims
Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS) of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT).
Methods
A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS.
Results
The median number of MET cycles was two (1-15). The OS values for the MET group and sorafenib group were 158 days (132-184) and 117 days (92-142), respectively (P=0.029). The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014) and Child-Pugh class B (HR=1.856, P=0.008).
Conclusions
MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.

Citations

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Optimal candidates and surrogate endpoints for HAIC versus Sorafenib in hepatocellular carcinoma: an updated systematic review and meta-analysis
Tengfei Si, Qing Shao, Wayel Jassem, Yun Ma, Nigel Heaton
International Journal of Surgery.2025; 111(1): 1203. CrossRef
The deubiquitinating enzyme ATXN3 promotes hepatocellular carcinoma progression by stabilizing TAZ
Yuanhao Peng, Hui Nie, Kuo Kang, Xuanxuan Li, Yongguang Tao, Yangying Zhou
Cancer Gene Therapy.2025; 32(1): 136. CrossRef
Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma: A network meta-analysis
Shun-An Zhou, Qing-Mei Zhou, Lei Wu, Zhi-Hong Chen, Fan Wu, Zhen-Rong Chen, Lian-Qun Xu, Bi-Ling Gan, Hao-Sheng Jin, Ning Shi
World Journal of Gastrointestinal Oncology.2024; 16(8): 3672. CrossRef
Efficacy and Safety of Metronomic Capecitabine in Hepatocellular Carcinoma: A Systematic Review and Meta-analysis
Nandini Gupta, Neelkant Verma, Bhoomika Patel
Journal of Gastrointestinal Cancer.2024; 55(4): 1485. CrossRef
Clinical significance of exosomal noncoding RNAs in hepatocellular carcinoma: a narrative review
Jae Sung Yoo, Min Kyu Kang
Journal of Yeungnam Medical Science.2024; 42: 4. CrossRef
Hepatic arterial infusion chemotherapy versus sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombus: An updated meta-analysis and systematic review
Wei Zhang, Deliang Ouyang, Zhangkan Huang, Xu Che
Frontiers in Oncology.2023;[Epub] CrossRef
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Zi-Wen Tao, Bao-Quan Cheng, Tao Zhou, Yan-Jing Gao
Hepatobiliary & Pancreatic Diseases International.2022; 21(2): 134. CrossRef
A novel chemotherapy strategy for advanced hepatocellular carcinoma: a multicenter retrospective study
Juxian Sun, Chang Liu, Jie Shi, Nanya Wang, Dafeng Jiang, Feifei Mao, Jingwen Gu, Liping Zhou, Li Shen, Wan Yee Lau, Shuqun Cheng
Chinese Medical Journal.2022; 135(19): 2338. CrossRef
Patterns and Outcomes in Hepatocellular Carcinoma Patients with Portal Vein Invasion: A Multicenter Prospective Cohort Study
Dong Hyun Sinn, Hye Won Lee, Yong-Han Paik, Do Young Kim, Yoon Jun Kim, Kang Mo Kim, Si Hyun Bae, Ji Hoon Kim, Yeon Seok Seo, Jae Young Jang, Byoung Kuk Jang, Hyung Joon Yim, Hyung Joon Kim, Byung Seok Lee, Bo Hyun Kim, In Hee Kim, Eun-Young Cho, Jung Il
Digestive Diseases and Sciences.2021; 66(1): 315. CrossRef
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Young Ae Kim, Danbee Kang, Hyeyoung Moon, Donghyun Sinn, Minwoong Kang, Sang Myung Woo, Yoon Jung Chang, Boram Park, Sun-Young Kong, Eliseo Guallar, Soo-Yong Shin, Geunyeon Gwak, Joung Hwan Back, Eun Sook Lee, Juhee Cho, Gianfranco D. Alpini
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Linda Beenet
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Efficacy and tolerability of Sorafenib plus metronomic chemotherapy S-1 for advanced hepatocellular carcinoma in preclinical and clinical assessments
Hiroyuki Suzuki, Hideki Iwamoto, Masahito Nakano, Toru Nakamura, Atsutaka Masuda, Takahiko Sakaue, Toshimitsu Tanaka, Dan Nakano, Ryoko Kuromatsu, Takashi Niizeki, Shusuke Okamura, Shigeo Shimose, Tomotake Shirono, Yu Noda, Naoki Kamachi, Hirohisa Yano, A
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Shengzhou Li, Jiaxuan Xu, Hongya Zhang, Jiaze Hong, Yuexiu Si, Tong Yang, Yujing He, Derry Minyao Ng, Dingcheng Zheng
Chemotherapy.2021; 66(4): 124. CrossRef
Systematic review of hepatic arterial infusion chemotherapy versus sorafenib in patients with hepatocellular carcinoma with portal vein tumor thrombosis
Miao Liu, Junyi Shi, Tong Mou, Yang Wang, Zhongjun Wu, Ai Shen
Journal of Gastroenterology and Hepatology.2020; 35(8): 1277. CrossRef
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Pil Soo Sung, Moon Hyung Choi, Hyun Yang, Soon Kyu Lee, Ho Jong Chun, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Joon-Il Choi, Young Joon Lee, Si Hyun Bae
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ASPP2 enhances chemotherapeutic sensitivity through the down-regulation of XIAP expression in a p53 independent manner in hepatocellular carcinoma
Tongwang Yang, Yuxue Gao, Daojie Liu, Yang Wang, Jing Wu, Xiaoni Liu, Ying Shi, Dexi Chen
Biochemical and Biophysical Research Communications.2019; 508(3): 769. CrossRef
Selective embolization with magnetized microbeads using magnetic resonance navigation in a controlled‐flow liver model
François Michaud, Ning Li, Rosalie Plantefève, Zeynab Nosrati, Charles Tremblay, Katayoun Saatchi, Gerald Moran, Alexandre Bigot, Urs O. Häfeli, Samuel Kadoury, An Tang, Pierre Perreault, Sylvain Martel, Gilles Soulez
Medical Physics.2019; 46(2): 789. CrossRef
Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience
Cem Simsek, Ece Esin, Suayib Yalcin
Journal of Oncology.2019; 2019: 1. CrossRef
Sorafenib versus hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis
Bo-wen Zhuang, Wei Li, Xiao-hua Xie, Hang-tong Hu, Ming-de Lu, Xiao-yan Xie
Japanese Journal of Clinical Oncology.2019; 49(9): 845. CrossRef
Sorafenib-loaded hydroxyethyl starch-TG100-115 micelles for the treatment of liver cancer based on synergistic treatment
Guofei Li, Limei Zhao
Drug Delivery.2019; 26(1): 756. CrossRef
Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers
Lucia Cerrito, Brigida Eleonora Annicchiarico, Roberto Iezzi, Antonio Gasbarrini, Maurizio Pompili, Francesca Romana Ponziani
World Journal of Gastroenterology.2019; 25(31): 4360. CrossRef
Comparison of clinical outcomes between sorafenib and hepatic artery infusion chemotherapy in advanced hepatocellular carcinoma
Min Kyu Kang, Jung Gil Park, Heon Ju Lee
Medicine.2018; 97(17): e0611. CrossRef
Randomized, prospective, comparative study on the effects and safety of sorafenib vs. hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis
Jong Hwan Choi, Woo Jin Chung, Si Hyun Bae, Do Seon Song, Myeong Jun Song, Young Seok Kim, Hyung Joon Yim, Young Kul Jung, Sang Jun Suh, Jun Yong Park, Do Young Kim, Seung Up Kim, Sung Bum Cho
Cancer Chemotherapy and Pharmacology.2018; 82(3): 469. CrossRef
Rationale for the use of metronomic chemotherapy in gastrointestinal cancer
Roberto Filippi, Pasquale Lombardi, Ilaria Depetris, Elisabetta Fenocchio, Virginia Quarà, Giovanna Chilà, Massimo Aglietta, Francesco Leone
Expert Opinion on Pharmacotherapy.2018; 19(13): 1451. CrossRef
Liver‑targeted delivery of liposome‑encapsulated curcumol using galactosylated‑stearate
Wen‑Jie Li, You‑Wen Lian, Quan‑Sheng Guan, Ning Li, Wen‑Jun Liang, Wen‑Xin Liu, Yong‑Bin Huang, Yi Cheng, Hui Luo
Experimental and Therapeutic Medicine.2018;[Epub] CrossRef
Can metronomic chemotherapy be an alternative to sorafenib in advanced hepatocellular carcinoma?
Do Young Kim
Clinical and Molecular Hepatology.2017; 23(2): 123. CrossRef

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Case Report

Liver fibrosis, cirrhosis, and portal hypertension

Recurrent acute portal vein thrombosis in liver cirrhosis treated by rivaroxaban: Hyeyoung Yang, Seo Ree Kim, Myeong Jun Song; Clin Mol Hepatol 2016;22(4):499-502.
Published online November 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0016

Abstract
PDF

Cirrhosis can occur with the development of portal vein thrombosis (PVT). PVT may aggravate portal hypertension, and it can lead to hepatic decompensation. The international guideline recommends for anticoagulation treatment to be maintained for at least 3 months in all patients with acute PVT. Low-molecular-weight-heparin and changing to warfarin is the usual anticoagulation treatment. However, warfarin therapy is problematic due to a narrow therapeutic window and the requirement for frequent dose adjustment, which has prompted the development of novel oral anticoagulants for overcoming these problems. We report a 63-year-old female who experienced complete resolution of recurrent acute PVT in liver cirrhosis after treatment with rivaroxaban.

Citations

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Original Articles

Viral hepatitis

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection: Hee Chul Nam, Hae Lim Lee, Hyun Yang, Myeong Jun Song; Clin Mol Hepatol 2016;22(2):259-266.
Published online June 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0020

Abstract
PDF

Background/Aims
The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice.
Methods
Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR₁₂) and safety.
Results
This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR₁₂ was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients.
Conclusions
In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

Citations

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Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea
Jung Hyun Kwon, Sun Hong Yoo, Soon Woo Nam, Hee Yeon Kim, Chang Wook Kim, Chan Ran You, Sang Wook Choi, Se Hyun Cho, Joon‐Yeol Han, Do Seon Song, U Im Chang, Jin Mo Yang, Sung Won Lee, Hae Lim Lee, Nam Ik Han, Seok‐Hwan Kim, Myeong Jun Song, Pil Soo Sung,
Journal of Medical Virology.2019; 91(6): 1104. CrossRef
Real‐life effectiveness and safety of the daclatasvir/asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: An emphasis on the pretreatment NS5A resistance‐associated substitution test
Eun Sun Jang, Kyung‐Ah Kim, Young Seok Kim, In Hee Kim, Byung Seok Lee, Youn Jae Lee, Woo Jin Chung, Sook‐Hyang Jeong
Journal of Medical Virology.2019; 91(12): 2158. CrossRef
An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection
Youn Jae Lee, Jeong Heo, Do Young Kim, Woo Jin Chung, Won Young Tak, Yoon Jun Kim, Seung Woon Paik, Eungeol Sim, Susila Kulasingam, Rohit Talwani, Barbara Haber, Peggy Hwang
Clinical and Molecular Hepatology.2019; 25(4): 400. CrossRef
Early development of de novo hepatocellular carcinoma after direct‐acting agent therapy: Comparison with pegylated interferon‐based therapy in chronic hepatitis C patients
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Isabella Esposito, Sebastián Marciano, Julieta Trinks
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Efficacy and safety of daclatasvir plus asunaprevir for Korean patients with HCV genotype Ib infection: a retrospective multi-institutional study
Byeong Wook Cho, Seok Bae Kim, Il Han Song, Sae Hwan Lee, Hong Soo Kim, Tae Hee Lee, Young Woo Kang, Seok Hyun Kim, Byung Seok Lee, Hee Bok Chae
Clinical and Molecular Hepatology.2017; 23(1): 51. CrossRef
Daclatasvir-based Treatment Regimens for Hepatitis C Virus Infection: A Systematic Review and Meta-Analysis
Seyed Moayed Alavian, Mohammad Saeid Rezaee-Zavareh
Hepatitis Monthly.2016;[Epub] CrossRef

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Steatotic liver disease

Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease: Young Seok Kim, Eun Sun Jung, Wonhee Hur, Si Hyun Bae, Jong Young Choi, Myeong Jun Song, Chang Wook Kim, Se Hyun Jo, Chang Don Lee, Young Sok Lee, Sang Wook Choi, Jin Mo Yang, Jeong Won Jang, Sang Gyune Kim, Seung Won Jung, Hee Kyung Kim, Hee Bok Chae, Seung Kew Yoon; Clin Mol Hepatol 2013;19(2):120-130.
Published online June 27, 2013; DOI: https://doi.org/10.3350/cmh.2013.19.2.120

Abstract
PDF

Background/Aims

The aims of this study were (1) to identify the useful clinical parameters of noninvasive approach for distinguishing nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD), and (2) to determine whether the levels of the identified parameters are correlated with the severity of liver injury in patients with NASH.

Methods

One hundred and eight consecutive patients with biopsy-proven NAFLD (age, 39.8±13.5 years, mean±SD; males, 67.6%) were prospectively enrolled from 10 participating centers across Korea.

Results

According to the original criteria for NAFLD subtypes, 67 patients (62.0%) had NASH (defined as steatosis with hepatocellular ballooning and/or Mallory-Denk bodies or fibrosis ≥2). Among those with NAFLD subtype 3 or 4, none had an NAFLD histologic activity score (NAS) below 3 points, 40.3% had a score of 3 or 4 points, and 59.7% had a score >4 points. Fragmented cytokeratin-18 (CK-18) levels were positively correlated with NAS (r=0.401), as well as NAS components such as lobular inflammation (r=0.387) and ballooning (r=0.231). Fragmented CK-18 was also correlated with aspartate aminotransferase (r=0.609), alanine aminotransferase (r=0.588), serum ferritin (r=0.432), and the fibrosis stage (r=0.314). A fragmented CK-18 cutoff level of 235.5 U/L yielded sensitivity, specificity, and positive and negative predictive values of 69.0%, 64.9%, 75.5% (95% CI 62.4-85.1), and 57.1% (95% CI 42.2-70.9), respectively, for the diagnosis of NASH.

Conclusions

Serum fragmented CK-18 levels can be used to distinguish between NASH and NAFL. Further evaluation is required to determine whether the combined measurement of serum CK-18 and ferritin levels improves the diagnostic performance of this distinction.

Citations

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Differences in the patterns and outcomes of enhanced viral replication between hepatitis C virus and hepatitis B virus in patients with hepatocellular carcinoma during transarterial chemolipiodolization: Pil Soo Sung, Si Hyun Bae, Jeong Won Jang, Do Seon Song, Hee Yeon Kim, Sun Hong Yoo, Chung-Hwa Park, Jung Hyun Kwon, Myeong Jun Song, Chan Ran You, Jong Young Choi, Seung Kew Yoon; Korean J Hepatol 2011;17(4):299-306.
Published online December 26, 2011; DOI: https://doi.org/10.3350/kjhep.2011.17.4.299

Abstract
PDF

Background/Aims

Enhanced replication of hepatitis C virus (HCV) is well described in the setting of moderate to severe immunosuppression. The aims of this retrospective study were to determine the incidence of enhanced HCV replication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemolipiodolization (TACL) and to identify the factors associated with enhanced replication of HCV. The clinical pattern of enhanced HCV replication was compared with hepatitis B virus (HBV) reactivation during TACL.

Methods

This study enrolled 49 anti-HCV-seropositive patients who were diagnosed with HCC between January 2005 and December 2010 and who underwent TACL using epirubicin and/or cisplatin with consecutive HCV RNA copies checked. For comparison, 46 hepatitis B surface antigen¹-positive patients with HCC who were treated with TACL were also enrolled. The frequency, associated factors, and clinical outcomes of enhanced HCV replication were analyzed and compared with those of HBV reactivation during TACL.

Results

Enhanced replication of HCV occurred in 13 (26.5%) of the 49 anti-HCV-seropositive patients during TACL. Of these 13 patients, 4 developed hepatitis, but none of the subjects developed decompensation due to the hepatitis. No significant clinical factors for enhanced HCV replication during TACL were found. Compared with HBV reactivation, the frequency of hepatitis attributed to enhanced HCV replication was significantly lower than that for HBV reactivation (8.2% vs. 23.9%, P=0.036).

Conclusions

TACL can enhance HCV replication; however, the likelihood of hepatitis and decompensation stemming from enhanced HCV replication was lower than that for HBV reactivation in patients undergoing TACL.

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