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"Nonalcoholic fatty liver disease"

Special Issue

Steatotic liver disease

KASL clinical practice guidelines for the management of metabolic dysfunction-associated steatotic liver disease 2025
Won Sohn, Young-Sun Lee, Soon Sun Kim, Jung Hee Kim, Young-Joo Jin, Gi-Ae Kim, Pil Soo Sung, Jeong-Ju Yoo, Young Chang, Eun Joo Lee, Hye Won Lee, Miyoung Choi, Su Jong Yu, Young Kul Jung, Byoung Kuk Jang, on behalf of The Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2025;31(Suppl):S1-S31.
Published online February 19, 2025
DOI: https://doi.org/10.3350/cmh.2025.0045

Citations

Citations to this article as recorded by  Crossref logo
  • Differential Infiltration of T-Cell Populations in Tumor and Liver Tissues Predicts Recurrence-Free Survival in Surgically Resected Hepatocellular Carcinoma
    Eun Ji Jang, Ho Joong Choi, Young Kyoung You, Deok Hwa Seo, Mi Hyun Kwon, Keungmo Yang, Jaejun Lee, Jeong Won Jang, Seung Kew Yoon, Ji Won Han, Pil Soo Sung
    Cancers.2025; 17(9): 1548.     CrossRef
  • Metabolic Dysfunction-Associated Steatotic Liver Disease, Recent Revision of Terminology and Its Implications
    Hyo Young Lee, Eileen L. Yoon
    The Korean Journal of Gastroenterology.2025; 85(2): 126.     CrossRef
  • Advances in identifying risk factors of metabolic dysfunction-associated alcohol-related liver disease
    Rui-Qi Ye, Yi-Fan Chen, Chang Ma, Xi Cheng, Wei Guo, Sha Li
    Biomedicine & Pharmacotherapy.2025; 188: 118191.     CrossRef
  • A Case Report of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) with Improved Cardiometabolic Risk Factors Following Treatment with Saenggangunbi-tang
    Eun Kyung Lee, Min Jeong Park, Youngchul Kim, Jang-Hoon Lee
    The Journal of Internal Korean Medicine.2025; 46(2): 303.     CrossRef
  • Food Nutrients and Bioactive Compounds for Managing Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comprehensive Review
    Erdenetsogt Dungubat, Kohei Fujikura, Masahiko Kuroda, Toshio Fukusato, Yoshihisa Takahashi
    Nutrients.2025; 17(13): 2211.     CrossRef
  • Associations between steatotic liver disease subtypes and incident atrial fibrillation in young adults: a nationwide cohort study
    Jeayeon Park, Goh Eun Chung, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Eun Ju Cho
    Cardiovascular Diabetology.2025;[Epub]     CrossRef
  • Second-line antidiabetic drugs: friend or foe of the liver
    Jiwon Yang, Gunho Kim, Ju Hyun Shim, Jihyun An
    Journal of Liver Cancer.2025; 25(2): 187.     CrossRef
  • Extrahepatic manifestation of metabolic dysfunction-associated steatotic liver disease
    Anoushka Shenoy, Aijaz Ahmed, Donghee Kim
    Metabolism and Target Organ Damage.2025;[Epub]     CrossRef
  • 2025 Clinical Practice Guidelines for Diabetes: Management of Metabolic Dysfunction-Associated Steatotic Liver Disease
    Jaehyun Bae
    The Journal of Korean Diabetes.2025; 26(3): 172.     CrossRef
  • Paired snRNA-seq and scRNA-seq analysis of MASLD patients to identify early-stage markers for disease progression
    Suebin Park, Su-Hyeon Lee, Se-eun Han, Beom Kyung Kim, Byungjin Hwang
    Hepatology Communications.2025;[Epub]     CrossRef
  • Sex Hormones and Metabolic Dysfunction-Associated Steatotic Liver Disease
    Ralf Weiskirchen, Amedeo Lonardo
    International Journal of Molecular Sciences.2025; 26(19): 9594.     CrossRef
  • Discovery of ultrasound-derived fat fraction as a non-invasive tool for MASLD diagnosis
    Huiru Jin, Mengfan Jiao, Chengxiao Yu, Tingting Ren, Qingling Chen, Zixing Dai, Erfu Xie, Longfeng Jiang, Yuwen Li
    European Journal of Medical Research.2025;[Epub]     CrossRef
  • Risk of Esophageal and Gastric Cancer by Histologic Subtype in Steatotic Liver Disease: A UK Biobank Study
    Donghoon Kang, Ji Won Han, Kenneth R. Muir, Artitaya Lophatananon, Jongin Lee
    Cancers.2025; 17(21): 3416.     CrossRef
  • 9,015 View
  • 275 Download
  • 10 Web of Science
  • Crossref

Letter to the Editor

  • 6,877 View
  • 53 Download

Correspondences

Steatotic liver disease

Citations

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  • Reply to correspondence on “Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: a network meta-analysis”
    Tian-Yi Ren, Mohammed Eslam, Jian-Gao Fan
    Clinical and Molecular Hepatology.2024; 30(4): 1039.     CrossRef
  • 4,347 View
  • 50 Download
  • Crossref

Review

Steatotic liver disease

Role of noninvasive tests in the prognostication of metabolic dysfunction-associated steatotic liver disease
Yue Wang, Sherlot Juan Song, Yichong Jiang, Jimmy Che-To Lai, Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2025;31(Suppl):S51-S75.
Published online June 27, 2024
DOI: https://doi.org/10.3350/cmh.2024.0246
In managing metabolic dysfunction-associated steatotic liver disease, which affects over 30% of the general population, effective noninvasive biomarkers for assessing disease severity, monitoring disease progression, predicting the development of liver-related complications, and assessing treatment response are crucial. The advantage of simple fibrosis scores lies in their widespread accessibility through routinely performed blood tests and extensive validation in different clinical settings. They have shown reasonable accuracy in diagnosing advanced fibrosis and good performance in excluding the majority of patients with a low risk of liver-related complications. Among patients with elevated serum fibrosis scores, a more specific fibrosis and imaging biomarker has proved useful to accurately identify patients at risk of liver-related complications. Among specific fibrosis blood biomarkers, enhanced liver fibrosis is the most widely utilized and has been approved in the United States as a prognostic biomarker. For imaging biomarkers, the availability of vibration-controlled transient elastography has been largely improved over the past years, enabling the use of liver stiffness measurement (LSM) for accurate assessment of significant and advanced fibrosis, and cirrhosis. Combining LSM with other routinely available blood tests enhances the ability to diagnose at-risk metabolic dysfunction-associated steatohepatitis and predict liver-related complications, some reaching an accuracy comparable to that of liver biopsy. Magnetic resonance imaging-based modalities provide the most accurate quantification of liver fibrosis, though the current utilization is limited to research settings. Expanding their future use in clinical practice depends on factors such as cost and facility availability.

Citations

Citations to this article as recorded by  Crossref logo
  • Fe-Mn-IGF-AMD nanoparticles in accurate detection and treatment of liver cirrhosis via regulating relaxation coefficients and attenuating hepatocyte senescence
    Baihe Wang, Tingting Ji, Zihao Zhang, Yuyao Duan, Zhiqun Xing, Jiazhi Duan, Songbo Zhao, Yang Jia, Qian Wang
    Colloids and Surfaces B: Biointerfaces.2026; 257: 115182.     CrossRef
  • Prediction of major liver-related events in the population using prognostic models
    Fredrik Åberg, Ville Männistö
    Gastroenterology Report.2025;[Epub]     CrossRef
  • Clinical and Economic Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Spanish Mediterranean Region: A Population-Based Study
    Javier Díaz Carnicero, Inma Saurí-Ferrer, Josep Redon, Jorge Navarro, Gonzalo Fernández, Carlos Hurtado, Karine Ferreira, Carolina Alvarez-Ortega, Antón Gómez, Carlos J. Martos-Rodríguez, David Martí-Aguado, Desamparados Escudero, Marta Cedenilla
    Journal of Clinical Medicine.2025; 14(7): 2441.     CrossRef
  • Non-invasive risk-based surveillance of hepatocellular carcinoma in patients with metabolic dysfunction-associated steatotic liver disease
    Jimmy Che-To Lai, Boyu Yang, Hye Won Lee, Huapeng Lin, Emmanuel A Tsochatzis, Salvatore Petta, Elisabetta Bugianesi, Masato Yoneda, Ming-Hua Zheng, Hannes Hagström, Jerome Boursier, Jose Luis Calleja, George Boon-Bee Goh, Wah-Kheong Chan, Rocìo Gallego-Du
    Gut.2025; 74(12): 2050.     CrossRef
  • Effect of Antidiabetic Drug Classes on the Risk of Liver-Related Events in Individuals With T2D and MASLD
    Yu Shi, Seung Up Kim, Terry Cheuk-Fung Yip, Emmanuel Tsochatzis, Salvatore Petta, Atsushi Nakajima, Hannes Hagström, Elisabetta Bugianesi, Wah-Kheong Chan, Jérôme Boursier, Boon-Bee George Goh, Arun J. Sanyal, Manuel Romero-Gomez, José Luis Calleja, Victo
    Clinical Gastroenterology and Hepatology.2025;[Epub]     CrossRef
  • Risk stratification by noninvasive tests in patients with metabolic dysfunction-associated steatotic liver disease
    Hye Won Lee, Jae Seung Lee, Mi Na Kim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Seung Up Kim
    Clinical and Molecular Hepatology.2025; 31(3): 1018.     CrossRef
  • Non-invasive tests of fibrosis in the management of MASLD: revolutionising diagnosis, progression and regression monitoring
    Gong Feng, Vincent Wai-Sun Wong, Giovanni Targher, Christopher D Byrne, Ming-Hua Zheng
    Gut.2025; 74(10): 1741.     CrossRef
  • Relative change rate of liver stiffness measurements predicts the risk of liver decompensation in compensated advanced chronic liver disease
    Yanqiu Li, Zihang Qiao, Jinze Li, Bingbing Zhu, Yu Lu, Ying Feng, Xianbo Wang
    Clinical and Experimental Medicine.2025;[Epub]     CrossRef
  • Correspondence to letter to the editor on “Risk Stratification of Metabolic Dysfunction-Associated Steatotic Liver Disease: The KASL Pathway
    Hye Won Lee, Seung Up Kim
    Clinical and Molecular Hepatology.2025;[Epub]     CrossRef
  • Endohepatology in the Management of Liver Diseases
    Thomas J. Wang, Ajaypal Singh
    Seminars in Liver Disease.2025;[Epub]     CrossRef
  • Letter to the Editor: Are we overestimating LSM-based HCC risk in MASLD? Addressing immortal time bias
    Heechul Nam, Sung Won Lee
    Hepatology.2025;[Epub]     CrossRef
  • Liver stiffness measurement-based risk score for predicting liver decompensation risk: a single-center retrospective Chinese study
    Yanqiu Li, Zihang Qiao, Jinze Li, Yongqi Li, Ying Feng, Xianbo Wang
    Clinical and Experimental Medicine.2025;[Epub]     CrossRef
  • Liver Transplantation in the Era of Metabolic Dysfunction–Associated Fatty Liver Disease: Challenges, Ethical Dilemmas, and Future Directions
    Said A. Al-Busafi, Mohammed Eslam
    Transplantology.2025; 6(4): 35.     CrossRef
  • Preface
    Seung Up Kim
    Clinical and Molecular Hepatology.2024; 30(Suppl): S3.     CrossRef
  • 11,218 View
  • 290 Download
  • 11 Web of Science
  • Crossref

Special Review

Steatotic liver disease

Waiting for the changes after the adoption of steatotic liver disease
Eileen L. Yoon, Dae Won Jun
Clin Mol Hepatol 2023;29(4):844-850.
Published online September 6, 2023
DOI: https://doi.org/10.3350/cmh.2023.0291
Steatotic liver disease was suggested as an overarching term encompassing various etiologies of hepatic steatosis. Experts from multinational liver societies went through the Delphi process, including four rounds of surveys, and consented to adopt a new nomenclature and definition instead of the conventional nonalcoholic fatty liver disease (NAFLD). This was to improve the understanding of the patients and primary care physicians, with an explanation of the pathophysiology in the name of the disease. Also, it could minimize the stigmatization of patients by using the histological neutral term “steatosis” instead of “fatty”. Herein, we will discuss the changes and continuity between the two nomenclatures, metabolic dysfunction-associated steatotic liver disease (MASLD) and NAFLD, as well as the challenges to MASLD which need to be addressed in future.

Citations

Citations to this article as recorded by  Crossref logo
  • Reply to: “Is liver fibrosis more advanced in MetALD than in MASLD?”
    Joo Hyun Oh, Dae Won Jun
    Journal of Hepatology.2025; 82(1): e58.     CrossRef
  • Statin use and liver-related prognosis among patients with MASLD
    Byungyoon Yun, Heejoo Park, Jian Lee, Beom Kyung Kim, Jin-Ha Yoon
    JHEP Reports.2025; 7(4): 101313.     CrossRef
  • Performance of Noninvasive Indices for Discrimination of Metabolic Dysfunction-Associated Steatotic Liver Disease in Young Adults
    Jaejun Lee, Chang In Han, Dong Yeup Lee, Pil Soo Sung, Si Hyun Bae, Hyun Yang
    Gut and Liver.2025; 19(1): 116.     CrossRef
  • Optimal BMI cutoff for lean MASLD/MetALD and adverse hepatic outcomes in East-Asian populations
    Byungyoon Yun, Juyeon Oh, Heejoo Park, Beom Kyung Kim, Jin-Ha Yoon
    European Journal of Internal Medicine.2025; 133: 141.     CrossRef
  • Cigarette Smoke Contributes to the Progression of MASLD: From the Molecular Mechanisms to Therapy
    Jiatong Xu, Yifan Li, Zixuan Feng, Hongping Chen
    Cells.2025; 14(3): 221.     CrossRef
  • Psychosocial risks in metabolic dysfunction-associated steatotic liver disease
    Hanne Åström, Christine Takami Lageborn, Hannes Hagström
    Expert Review of Gastroenterology & Hepatology.2025; 19(3): 273.     CrossRef
  • Is type 2 diabetes a link between lung function and metabolic dysfunction–associated steatotic liver disease? Insights from population studies and Mendelian randomization
    Runmin Cao, Yurun Zhang, Ling Cao, Honghe Jiang
    European Journal of Gastroenterology & Hepatology.2025; 37(5): 652.     CrossRef
  • A novel 11β-HSD1 inhibitor ameliorates liver fibrosis by inhibiting the notch signaling pathway and increasing NK cell population
    Ji Eun Kim, Yun Kim, Jiwon Bae, Eileen Laurel Yoon, Hyun Sung Kim, Sung Ryol Lee, Tae Hyun Yoon, Dae Won Jun
    Archives of Pharmacal Research.2025; 48(2): 166.     CrossRef
  • Molecular Clustering of Metabolic Dysfunction-Associated Steatotic Liver Disease Based on Transcriptome Analysis
    Gina Ryu, Eileen Laurel Yoon, Wankyu Kim, Dae Won Jun
    Diagnostics.2025; 15(3): 342.     CrossRef
  • Dietary Patterns Rich in Soybean Products, Vegetables, Fish, Fruits, and Miso Soup Were Inversely Associated with Fatty Liver Index: The Nagahama Study
    Yoko UEBA, Kaori IKEDA, Yasuharu TABARA, Takeo NAKAYAMA, Daisuke TANAKA, Yoshimitsu TAKAHASHI, Shinji KOSUGI, Kazuya SETOH, Takahisa KAWAGUCHI, Fumihiko MATSUDA, Nobuya INAGAKI
    Journal of Nutritional Science and Vitaminology.2025; 71(1): 25.     CrossRef
  • Identification of Novel Therapeutic Targets for MAFLD Based on Bioinformatics Analysis Combined with Mendelian Randomization
    Jialin Ren, Min Wu
    International Journal of Molecular Sciences.2025; 26(7): 3166.     CrossRef
  • Comparative Hepatic Outcomes of SGLT2i or DPP4i Compared to GLP‐1RA in CHB and T2DM Patients
    Byungyoon Yun, Juyeon Oh, Heejoo Park, Jian Lee, Beom Kyung Kim, Jin‐Ha Yoon
    Liver International.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
  • Navigating the Paradox of IL‐22: Friend or Foe in Hepatic Health?
    Jianqi Qin, Weixiong Zhu, Wence Zhou
    Journal of Gastroenterology and Hepatology.2025; 40(6): 1393.     CrossRef
  • Association between dietary amino acid intake and the risk of metabolic dysfunction-associated steatotic liver disease
    Ruoqi Zhou, Xinrong Zhang, Xinxin Liu, Rui Huang, Yuwei Wang, Dajing Xia, Xue Li, Yihua Wu, Yu Shi
    Journal of Advanced Research.2025;[Epub]     CrossRef
  • Metabolic Dysfunction-Associated Steatotic Liver Disease, Recent Revision of Terminology and Its Implications
    Hyo Young Lee, Eileen L. Yoon
    The Korean Journal of Gastroenterology.2025; 85(2): 126.     CrossRef
  • Young Adults With Metabolic Dysfunction–Associated Steatotic Liver Disease Have an Increased Risk of Early-Onset Cancer: A Nationwide Cohort Study Differentiating the Risk of 23 Site-Specific Cancers
    Joon Ho Moon, Seogsong Jeong, Heejoon Jang, Dong Hyeon Lee, Sae Kyung Joo, Bo Kyung Koo, Qiang Xia, Meng Sha, Yoosoo Chang, Won Kim
    Clinical Gastroenterology and Hepatology.2025; 23(13): 2540.     CrossRef
  • The Role of Global Physical Capacity Score in Key Parameters of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
    Nicola Verrelli, Caterina Bonfiglio, Isabella Franco, Claudia Beatrice Bagnato, Dolores Stabile, Endrit Shahini, Antonella Bianco
    Journal of Clinical Medicine.2025; 14(11): 3821.     CrossRef
  • Cost-effectiveness analysis of MASLD screening using FIB-4 based two-step algorithm in the medical check-up
    Mimi Kim, Huiyul Park, Eileen L. Yoon, Ramsey Cheung, Donghee Kim, Hye-Lin Kim, Dae Won Jun
    Scientific Reports.2025;[Epub]     CrossRef
  • Gut-Liver Axis: The Role of Intestinal Microbiota and Their Metabolites in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease
    Chao Cui, Shuai Gao, Jingfei Shi, Kai Wang
    Gut and Liver.2025; 19(4): 479.     CrossRef
  • Comparison of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter-2 Inhibitors in Diabetic Patients with Steatotic Liver Disease
    Yunmi Ko, Moon Haeng Hur, Youngsu Park, Jeayeon Park, Hyunjae Shin, Yun Bin Lee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
    Gut and Liver.2025; 19(5): 758.     CrossRef
  • Misclassification of Alcohol Use Disorder in MASLD and MetALD: Prevalence, Clinical Characteristics, and Outcomes
    Jun-Hyuk Lee, Sung-Ho Ahn, Jimin Park, So Young Jeon, Eileen L. Yoon, Hye Sun Lee, Dae Won Jun
    Gut and Liver.2025; 19(5): 735.     CrossRef
  • Paired snRNA-seq and scRNA-seq analysis of MASLD patients to identify early-stage markers for disease progression
    Suebin Park, Su-Hyeon Lee, Se-eun Han, Beom Kyung Kim, Byungjin Hwang
    Hepatology Communications.2025;[Epub]     CrossRef
  • Changing from NAFLD to MASLD: Similar prognosis of unresectable extrahepatic gastrointestinal cancer under chemotherapy between NAFLD and MASLD
    Hiroyuki Suzuki, Toshimitsu Tanaka, Shotaro Yamaguchi, Keisuke Miwa, Takumi Kawaguchi
    Journal of Hepatology.2024; 80(4): e150.     CrossRef
  • Three-Step Algorithm for Screening High-Risk Group of Metabolic Dysfunction-Associated Steatotic Liver Disease in General Population
    Joo Hyun Oh, Dae Won Jun
    Gut and Liver.2024; 18(2): 197.     CrossRef
  • Changing from NAFLD to MASLD: Similar prognosis of patients with HCC under atezolizumab/bevacizumab treatment between NAFLD and MASLD
    Hiroyuki Suzuki, Shigeo Shimose, Hideki Iwamoto, Takashi Niizeki, Takumi Kawaguchi
    Clinical and Molecular Hepatology.2024; 30(2): 263.     CrossRef
  • Clinical impact of five cardiometabolic risk factors in metabolic dysfunction-associated steatotic liver disease (MASLD): Insights into regional and ethnic differences
    Joo Hyun Oh, Dae Won Jun
    Clinical and Molecular Hepatology.2024; 30(2): 168.     CrossRef
  • Similar respiratory function including chronic obstructive pulmonary disease between non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease
    Tsubasa Tsutsumi, Dan Nakano, Machiko Kawaguchi, Hirokazu Takahashi, Takumi Kawaguchi
    Clinical and Molecular Hepatology.2024; 30(2): 266.     CrossRef
  • Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study
    Michihiro Iwaki, Hideki Fujii, Hideki Hayashi, Hidenori Toyoda, Satoshi Oeda, Hideyuki Hyogo, Miwa Kawanaka, Asahiro Morishita, Kensuke Munekage, Kazuhito Kawata, Tsubasa Tsutsumi, Koji Sawada, Tatsuji Maeshiro, Hiroshi Tobita, Yuichi Yoshida, Masafumi Na
    Clinical and Molecular Hepatology.2024; 30(2): 225.     CrossRef
  • Changes in the terminology and diagnostic criteria of non-alcoholic fatty liver disease: Implications and opportunities
    Muhammed Mubarak
    World Journal of Gastrointestinal Pathophysiology.2024;[Epub]     CrossRef
  • Diagnostic performances of Fibrosis‐4 index and nonalcoholic fatty liver disease fibrosis score in metabolic dysfunction‐associated steatotic liver disease in Asian primary care clinics
    Huiyul Park, Mimi Kim, Hye‐Lin Kim, Seon Cho, Eileen L. Yoon, Dae Won Jun
    Hepatology Research.2024; 54(11): 1027.     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease: Evolution of the final terminology
    Piero Portincasa, Gyorgy Baffy
    European Journal of Internal Medicine.2024; 124: 35.     CrossRef
  • Revisiting the steatosis‐associated fibrosis estimator score in young Asian subjects with steatotic liver disease and consideration for population variability
    Jiwon Yang, Won‐Mook Choi, Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Young‐Suk Lim, Han Chu Lee, Jonggi Choi
    Journal of Gastroenterology and Hepatology.2024; 39(10): 2112.     CrossRef
  • Barriers to care linkage and educational impact on unnecessary MASLD referrals
    Jun-Hyuk Lee, Eileen Laurel Yoon, Ju Hyun Oh, Kyunam Kim, Sang Bong Ahn, Dae Won Jun
    Frontiers in Medicine.2024;[Epub]     CrossRef
  • A New Korean Nomenclature for Steatotic Liver Disease

    The Korean Journal of Gastroenterology.2024; 84(1): 1.     CrossRef
  • A New Korean Nomenclature for Steatotic Liver Disease

    The Korean Journal of Medicine.2024; 99(4): 189.     CrossRef
  • Metabolic Dysfunction-Associated Steatotic Liver Disease Is Associated with Increased Risk of Kidney Cancer: A Nationwide Study
    Juyeon Oh, Beom Kyung Kim, Jin-Ha Yoon, Hyung Ho Lee, Heejoo Park, Jian Lee, Youngsun Park, Byungyoon Yun, Jinsoo Chung
    Cancers.2024; 16(18): 3161.     CrossRef
  • A New Korean Nomenclature for Steatotic Liver Disease

    Gut and Liver.2024; 18(5): 924.     CrossRef
  • A new Korean nomenclature for steatotic liver disease

    Clinical and Molecular Hepatology.2024; 30(Suppl): S214.     CrossRef
  • Combi-Elastography versus Transient Elastography for Assessing the Histological Severity of Metabolic Dysfunction-Associated Steatotic Liver Disease
    Yun Kyu Lee, Dong Hyeon Lee, Sae Kyung Joo, Heejoon Jang, Young Ho So, Siwon Jang, Dong Ho Lee, Jeong Hwan Park, Mee Soo Chang, Won Kim
    Gut and Liver.2024; 18(6): 1048.     CrossRef
  • Establishment and characterization of mouse metabolic dysfunction-associated steatohepatitis-related hepatocellular carcinoma organoids
    Sumin Kim, Nahyun Jeong, Jeayeon Park, Hyojin Noh, Ja Oh Lee, Su Jong Yu, Ja-Lok Ku
    Scientific Reports.2024;[Epub]     CrossRef
  • Metabolic Dysfunction-associated Steatotic Liver Disease–related Hepatocellular Carcinoma: Current Research Insights
    Ho Soo Chun, Minjong Lee, Tae Hun Kim
    Journal of Digestive Cancer Research.2024; 12(3): 184.     CrossRef
  • From metabolic dysfunction-associated fatty liver disease to metabolic dysfunction-associated steatotic liver disease: Controversy and consensus
    Li Chen
    World Journal of Hepatology.2023; 15(12): 1253.     CrossRef
  • Letter regarding “Waiting for the changes after the adoption of steatotic liver disease”
    Kuo Chao Yew, Sunny H. Wong, Vincent Wai-Sun Wong, Hazel H. Oon
    Clinical and Molecular Hepatology.2023; 30(1): 118.     CrossRef
  • Correspondence on Letter regarding “Waiting for the changes after the adoption of steatotic liver disease”
    Eileen L. Yoon, Dae Won Jun
    Clinical and Molecular Hepatology.2023; 30(1): 126.     CrossRef
  • Changing from NAFLD to MASLD: Similar cumulative incidence of reflux esophagitis between NAFLD and MASLD
    Shuhei Fukunaga, Michita Mukasa, Dan Nakano, Tsubasa Tsutsumi, Takumi Kawaguchi
    Clinical and Molecular Hepatology.2023; 30(1): 121.     CrossRef
  • 7,705 View
  • 188 Download
  • 42 Web of Science
  • Crossref

Editorials

Steatotic liver disease

Lean or Non-obese Nonalcoholic Fatty Liver Disease Patients: Are They Really Lean?
Eugene Han, Yong-ho Lee
Clin Mol Hepatol 2023;29(4):980-983.
Published online August 16, 2023
DOI: https://doi.org/10.3350/cmh.2023.0250

Citations

Citations to this article as recorded by  Crossref logo
  • Frequency and risk factors of metabolic associated fatty liver disease among medical students in Egypt
    Mohamed M. Elhoseeny, Fatma Rageh, Samar M. Rezk, Amira A. A. Othman
    Scientific Reports.2025;[Epub]     CrossRef
  • Exploring Fibrosis Pathophysiology in Lean and Obese Metabolic-Associated Fatty Liver Disease: An In-Depth Comparison
    Milena Vesković, Milka Pejović, Nikola Šutulović, Dragan Hrnčić, Aleksandra Rašić-Marković, Olivera Stanojlović, Dušan Mladenović
    International Journal of Molecular Sciences.2024; 25(13): 7405.     CrossRef
  • The unfolded features on the synchronized fashion of gut microbiota and Drynaria rhizome against obesity via integrated pharmacology
    Ki-Kwang Oh, Sang-Jun Yoon, Seol Hee Song, Jeong Ha Park, Jeong Su Kim, Min Ju Kim, Dong Joon Kim, Ki-Tae Suk
    Food Chemistry.2024; 460: 140616.     CrossRef
  • Diagnosis and Management of Lean Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review
    Basile Njei, Prince Ameyaw, Yazan Al-Ajlouni, Lea-Pearl Njei, Sarpong Boateng
    Cureus.2024;[Epub]     CrossRef
  • Non-alcoholic fatty liver disease in people with normal body weight
    S. V. Turkina, I. A. Tyshchenko, M. N. Titarenko
    Experimental and Clinical Gastroenterology.2024; (10): 36.     CrossRef
  • 6,745 View
  • 124 Download
  • 3 Web of Science
  • Crossref

Steatotic liver disease

The effect of moderate alcohol consumption on nonalcoholic fatty liver disease
Ji-Won Park, Ki Tae Suk
Clin Mol Hepatol 2023;29(2):408-410.
Published online March 16, 2023
DOI: https://doi.org/10.3350/cmh.2023.0085

Citations

Citations to this article as recorded by  Crossref logo
  • Hidden Burden of Alcohol Use Disorder in MASLD and MetALD: Clinical and Nomenclatural Implications
    Yuri Cho
    Gut and Liver.2025; 19(5): 637.     CrossRef
  • Probiotic-Derived Strain-Specific Metabolites Ameliorate Metabolic Dysfunction–Associated Steatotic Liver Disease through Modulation of the Gut-Liver Axis
    Sang Jun Yoon, Jieun Choi, Sung-Min Won, Jeong Seok Yu, Hee Young Kim, Hyun Chae Joung, In Gyu Park, Jung A Eom, Sang Hak Han, Do Yup Lee, Ki Tae Suk
    Probiotics and Antimicrobial Proteins.2025;[Epub]     CrossRef
  • Alcohol Drinking Impacts on Adiposity and Steatotic Liver Disease: Concurrent Effects on Metabolic Pathways and Cardiovascular Risks
    Diego Martínez-Urbistondo, Nuria Perez-Diaz-del-Campo, Manuel F. Landecho, J. Alfredo Martínez
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  • Akkermansia muciniphila improve cognitive dysfunction by regulating BDNF and serotonin pathway in gut-liver-brain axis
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Hepatic neoplasm

Hepatocellular carcinoma surveillance in non-alcoholic fatty liver disease – who and how?
Margaret LP Teng, Darren Jun Hao Tan, Cheng Han Ng, Daniel Q. Huang
Clin Mol Hepatol 2023;29(2):404-407.
Published online March 14, 2023
DOI: https://doi.org/10.3350/cmh.2023.0069

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Steatotic liver disease

Lean vs. obese phenotypes of nonalcoholic fatty liver disease: similar or different?
Ho Soo Chun, Minjong Lee
Clin Mol Hepatol 2023;29(2):377-380.
Published online March 9, 2023
DOI: https://doi.org/10.3350/cmh.2023.0061

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Original Article

Steatotic liver disease

Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: A network meta-analysis
Min Jeong Park, Hayeon Kim, Myeong Gyu Kim, Kyungim Kim
Clin Mol Hepatol 2023;29(3):693-704.
Published online March 9, 2023
DOI: https://doi.org/10.3350/cmh.2022.0330
Background/Aims
Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP-1RA) and thiazolidinedione (TZD) can improve nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). However, comprehensive research comparing the effects of GLP-1RA and TZD is limited. Thus, this study aimed to compare the effects of GLP-1RA and TZD on NAFLD or NASH through a network meta-analysis.
Methods
The PubMed, Embase, Web of Science, and Scopus databases were searched for randomized controlled trials (RCTs) that explored the efficacy of GLP-1RAs or TZDs in adult patients with NAFLD or NASH. The outcomes were liver biopsy-based (NAFLD activity score [NAS], fibrosis stage, and NASH resolution), noninvasive technique-based (liver fat content on proton magnetic resonance spectroscopy [1H-MRS] and controlled attenuation parameter [CAP]), biological, and anthropometric indicators. A random effects model was used to calculate the mean difference (MD) and relative risk with 95% confidence interval (CI).
Results
Twenty-five RCTs with 2,237 overweight or obese patients were included. GLP-1RA was significantly superior in reducing liver fat content evaluated using 1H-MRS (MD –2.42, 95% CI –3.84 to –1.00), body mass index (MD –1.60, 95% CI –2.41 to –0.80), and waist circumference (MD –4.89, 95% CI –8.17 to –1.61) than TZD. In liver biopsy-based evaluation and liver fat content assessment using CAP, GLP-1RA tended to surpass TZD, albeit not significantly. Sensitivity analysis showed consistent results with the main results.
Conclusions
Compared with TZD, GLP-1RA had better effects on liver fat content, body mass index, and waist circumference in overweight or obese patients with NAFLD or NASH.

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Editorial

Steatotic liver disease

The growing burden of non-alcoholic fatty liver disease on mortality
Ju-Yeon Cho, Won Sohn
Clin Mol Hepatol 2023;29(2):374-376.
Published online March 6, 2023
DOI: https://doi.org/10.3350/cmh.2023.0084

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Reviews

Steatotic liver disease

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of the population worldwide and includes nonalcoholic fatty liver, nonalcoholic steatohepatitis (NASH), and cirrhosis. Since NAFLD-associated diseases begin with steatosis, the early diagnosis of steatosis helps to prevent the progression of NASH and fibrosis. In addition, more convenient and easily diagnosable serum biomarkers are becoming crucial in disease diagnosis. In this report, we summarize the known serum biomarkers for liver steatosis and provide guidance for their application in clinical practice.

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    Jaejun Lee, Chang In Han, Dong Yeup Lee, Pil Soo Sung, Si Hyun Bae, Hyun Yang
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Steatotic liver disease

Nonalcoholic fatty liver disease and non-liver comorbidities
Richie Manikat, Mindie H. Nguyen
Clin Mol Hepatol 2023;29(Suppl):s86-s102.
Published online January 5, 2023
DOI: https://doi.org/10.3350/cmh.2022.0442
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.

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Steatotic liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease globally, and its prevalence is rapidly increasing. Nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD, is characterized by hepatocellular injury, inflammation, and fibrosis. Patients with NASH or severe fibrosis should be treated according to international NAFLD guidelines. Currently, regulatory agencies have not approved any pharmaceutical treatment for NAFLD. Vitamin E and pioglitazone are efficacious for NASH resolution; however, their benefits must be weighed against the reported risks. In a phase 2 trial, a glucagon-like peptide-1 agonist commonly used for diabetes and obesity was found to improve liver histology in patients with NASH. Furthermore, therapeutic agents targeting NASH pathogenesis, including bile acid signaling, insulin resistance, and lipid metabolism, are in various phases of clinical development. In this article, we review the benefits and drawbacks of current pharmacotherapy and the efficacy of upcoming treatments for NASH.

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Steatotic liver disease

Risk factors in nonalcoholic fatty liver disease
Eunji Ko, Eileen L. Yoon, Dae Won Jun
Clin Mol Hepatol 2023;29(Suppl):S79-S85.
Published online December 14, 2022
DOI: https://doi.org/10.3350/cmh.2022.0398
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, with a global prevalence estimated at approximately 25%. NAFLD is also the leading cause of liver cirrhosis, hepatocellular carcinoma, and death. Additionally, the risk of cardiovascular disease increases with greater NAFLD severity. The liver- and cardiovascular disease-related mortality incident rate ratios among the NAFLD population were 0.77 and 4.79 per 1,000 person-years, respectively. We intend to discuss the risk factors associated with NAFLD in terms of development and progression. Obesity or higher body mass index is closely associated with NAFLD in a dose-dependent manner, but growing evidence suggests that central obesity plays a more important role in the development of NAFLD. Saturated fat and fructose have been reported to be closely related to NAFLD. Fructose intake promotes lipogenesis and impairs mitochondria fat oxidation. The presence of type 2 diabetes is the most powerful predictive risk factor for hepatic fibrosis in patients with NAFLD. Single nucleotide polymorphism is not only associated with the prevalence of NAFLD but also associated with increased liver disease mortality. Obstructive sleep apnea, intestinal dysbiosis, and sarcopenia are associated with the development of NAFLD

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Steatotic liver disease

Global incidence and prevalence of nonalcoholic fatty liver disease
Margaret LP Teng, Cheng Han Ng, Daniel Q. Huang, Kai En Chan, Darren JH Tan, Wen Hui Lim, Ju Dong Yang, Eunice Tan, Mark D. Muthiah
Clin Mol Hepatol 2023;29(Suppl):S32-S42.
Published online December 14, 2022
DOI: https://doi.org/10.3350/cmh.2022.0365
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.

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Steatotic liver disease

Noninvasive imaging biomarkers for liver fibrosis in nonalcoholic fatty liver disease: current and future
Jung Hwan Yu, Han Ah Lee, Seung Up Kim
Clin Mol Hepatol 2023;29(Suppl):S136-S149.
Published online December 12, 2022
DOI: https://doi.org/10.3350/cmh.2022.0436
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide and becoming a major cause of liver disease-related morbidity and mortality. The presence of liver fibrosis in patients with NAFLD is closely related to prognosis, including the development of hepatocellular carcinoma and other complications of cirrhosis. Therefore, assessment of the presence of significant or advanced liver fibrosis is crucial. Although liver biopsy has been considered the “gold standard” method for evaluating the degree of liver fibrosis, it is not suitable for extensive use in all patients with NAFLD owing to its invasiveness and high cost. Therefore, noninvasive biochemical and imaging biomarkers have been developed to overcome the limitations of liver biopsy. Imaging biomarkers for the stratification of liver fibrosis have been evaluated in patients with NAFLD using different imaging techniques, such as transient elastography, shear wave elastography, and magnetic resonance elastography. Furthermore, artificial intelligence and deep learning methods are increasingly being applied to improve the diagnostic accuracy of imaging techniques and overcome the pitfalls of existing imaging biomarkers. In this review, we describe the usefulness and future prospects of noninvasive imaging biomarkers that have been studied and used to evaluate the degree of liver fibrosis in patients with NAFLD.

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Steatotic liver disease

Comparison between obese and non-obese nonalcoholic fatty liver disease
Wah-Kheong Chan
Clin Mol Hepatol 2023;29(Suppl):S58-S67.
Published online December 5, 2022
DOI: https://doi.org/10.3350/cmh.2022.0350
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver conditions that are characterized by excess accumulation of fat in the liver, and is diagnosed after exclusion of significant alcohol intake and other causes of chronic liver disease. In the majority of cases, NAFLD is associated with overnutrition and obesity, although it may be also found in lean or non-obese individuals. It has been estimated that 19.2% of NAFLD patients are lean and 40.8% are non-obese. The proportion of patients with more severe liver disease and the incidence of all-cause mortality, liver-related mortality, and cardiovascular mortality among non-obese and obese NAFLD patients varies across studies and may be confounded by selection bias, underestimation of alcohol intake, and unaccounted weight changes over time. Genetic factors may have a greater effect towards the development of NAFLD in lean or non-obese individuals, but the effect may be less pronounced in the presence of strong environmental factors, such as poor dietary choices and a sedentary lifestyle, as body mass index increases in the obese state. Overall, non-invasive tests, such as the Fibrosis-4 index, NAFLD fibrosis score, and liver stiffness measurement, perform better in lean or non-obese patients compared to obese patients. Lifestyle intervention works in non-obese patients, and less amount of weight loss may be required to achieve similar results compared to obese patients. Pharmacological therapy in non-obese NAFLD patients may require special consideration and a different approach compared to obese patients.

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Hepatic neoplasm

Preventive strategy for nonalcoholic fatty liver disease-related hepatocellular carcinoma
Yuri Cho, Bo Hyun Kim, Joong-Won Park
Clin Mol Hepatol 2023;29(Suppl):S220-S227.
Published online November 10, 2022
DOI: https://doi.org/10.3350/cmh.2022.0360
The incidence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, including Asia. Most patients with NAFLD-related HCC are at a much-advanced stage and older age at the time of diagnosis than those with virus-related HCC because they have not undergone HCC surveillance. This review provides an overview of the mechanism of hepatocarcinogenesis in NAFLD, preventive strategies for NAFLDrelated HCC, and strategies for the surveillance of patients with NAFLD.

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Editorials

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Review

Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases
Han Ah Lee, Young Chang, Pil Soo Sung, Eileen L. Yoon, Hye Won Lee, Jeong-Ju Yoo, Young-Sun Lee, Jihyun An, Do Seon Song, Young Youn Cho, Seung Up Kim, Yoon Jun Kim
Clin Mol Hepatol 2022;28(3):425-472.
Published online July 1, 2022
DOI: https://doi.org/10.3350/cmh.2022.0186
The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.

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Snapshot

Personalized medicine in nonalcoholic fatty liver disease
Carlos J. Pirola, Silvia Sookoian
Clin Mol Hepatol 2022;28(4):935-938.
Published online June 24, 2022
DOI: https://doi.org/10.3350/cmh.2022.0175

Citations

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  • Hidden in the Fat: Unpacking the Metabolic Tango Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Syndrome
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Editorial

Does nonalcoholic fatty liver disease predispose patients to carotid arteriosclerosis and ischemic stroke?
Qian Jin, Rui-Xu Yang, Jian-Gao Fan
Clin Mol Hepatol 2022;28(3):473-477.
Published online June 22, 2022
DOI: https://doi.org/10.3350/cmh.2022.0155

Citations

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  • Correspondence on Editorial regarding “Screening and prediction of nonalcoholic fatty liver disease using a peripheral insulin resistance index: Potential benefits and limitations”
    Jun-Hyuk Lee, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn
    Clinical and Molecular Hepatology.2023; 29(1): 185.     CrossRef
  • Impact of metabolic risk factors on hepatic and cardiac outcomes in patients with alcohol- and non-alcohol-related fatty liver disease
    Jihye Lim, Hyunji Sang, Ha Il Kim
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Original Article

Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF- κB signaling pathways
Seung Min Lee, Dong Hee Koh, Dae Won Jun, Yoon Jin Roh, Hyeon Tae Kang, Ju Hee Oh, Hyun Sung Kim
Clin Mol Hepatol 2022;28(4):827-840.
Published online June 22, 2022
DOI: https://doi.org/10.3350/cmh.2022.0068
Background/Aims
We aim to evaluate the effects of auranofin, a known antioxidant, on hepatic steatosis, inflammation, and fibrosis, contributing to non-alcoholic steatohepatitis (NASH) development in vivo and in vitro.
Methods
Transcriptome analysis of LX-2 cells was that expression patterns of genes changed by auranofin, and their related pathways were estimated. We used the gene set enrichment analysis (GSEA) program to determine the pathway involved in overall genetic change. In vitro, LX-2 and HepG2 cells were treated with transforming growth factor (TGF)-β1 and palmitic acid (PA), respectively, and the antifibrotic and antiadipogenic effect function of auranofin was evaluated.
Results
Transcriptome analysis revealed that auranofin decreased the expression of 15 genes, including thrombospondin 1, endothelin 1 (ET-1), fibronectin 1, and LOX. The molecular functions of these genes are involved in collagen binding. GSEA of the overall gene expression pattern revealed that many genes increased in the reactive oxygen species pathway and decreased in the inflammatory response. Auranofin decreased nuclear factor kappa B (NF-κB) and IκBα in TGF-β1-induced LX-2 cells, thereby reducing ET-1 and fibrosis. Furthermore, increased pNRF2 in PA-induced HepG2 cells led to increased antioxidant marker expression and decreased lipid accumulation. In the bile duct ligation model mice, auranofin reduced the fibrosis area and increased the survival rate. Auranofin reduced liver fibrosis and lipid accumulation in NASH model mice fed on a Western diet.
Conclusions
Auranofin inhibits lipogenesis and fibrosis formation and is a proposed candidate for NASH treatment.

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Editorial

A crystal ball to forecast treatment responsiveness in nonalcoholic fatty liver disease
Seonghwan Hwang, Won Kim
Clin Mol Hepatol 2022;28(3):478-480.
Published online June 16, 2022
DOI: https://doi.org/10.3350/cmh.2022.0143
  • 5,852 View
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Review

Nonalcoholic fatty liver disease versus metabolic-associated fatty liver disease: Prevalence, outcomes and implications of a change in name
Cheng Han Ng, Daniel Q. Huang, Mindie H. Nguyen
Clin Mol Hepatol 2022;28(4):790-801.
Published online May 11, 2022
DOI: https://doi.org/10.3350/cmh.2022.0070
Nonalcoholic fatty liver disease (NAFLD) affects about a third of the world’s adult population and is a major public health concern. NAFLD is defined by the presence of hepatic steatosis and the absence of other causes of liver disease. As NAFLD is closely associated with the presence of the metabolic syndrome, several experts have called for a change in nomenclature from NAFLD to metabolic-associated fatty liver disease (MAFLD) to better reflect the underlying pathophysiology of NAFLD as a metabolically driven disease and shift to a “positive” diagnostic criteria rather than one of exclusion. Recent studies have suggested that the global prevalence of MAFLD is higher than that of NAFLD, and patients with MAFLD have more metabolic comorbidities compared to those with NAFLD. Emerging data also suggest that all-cause and cardiovascular mortality may be higher in MAFLD compared with NAFLD. In this synopsis, we discuss differences in clinical features, prevalence and clinical outcomes between NAFLD and MAFLD. In addition, we highlight the advantages and disadvantages of a name change from NAFLD to MAFLD from the perspective of the scientific community, care providers and patients.

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Original Articles

Discovery of dipeptidyl peptidase-4 inhibitor specific biomarker in non-alcoholic fatty liver disease mouse models using modified basket trial
Ju Hee Oh, Dae Won Jun, Hye Young Kim, Seung Min Lee, Eileen L. Yoon, Jungwook Hwang, Jung Hwan Park, Hanbi Lee, Wankyu Kim, Hyunsung Kim
Clin Mol Hepatol 2022;28(3):497-509.
Published online April 28, 2022
DOI: https://doi.org/10.3350/cmh.2022.0019
Background/Aims
We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD).
Methods
An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy.
Results
DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels.
Conclusions
The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.

Citations

Citations to this article as recorded by  Crossref logo
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Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals
Ansel Shao Pin Tang, Kai En Chan, Jingxuan Quek, Jieling Xiao, Phoebe Tay, Margaret Teng, Keng Siang Lee, Snow Yunni Lin, May Zin Myint, Benjamin Tan, Vijay K Sharma, Darren Jun Hao Tan, Wen Hui Lim, Apichat Kaewdech, Daniel Huang, Nicholas WS Chew, Mohammad Shadab Siddiqui, Arun J Sanyal, Mark Muthiah, Cheng Han Ng
Clin Mol Hepatol 2022;28(3):483-496.
Published online March 2, 2022
DOI: https://doi.org/10.3350/cmh.2021.0406
Background/Aims
Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD.
Methods
Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD.
Results
From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P<0.0001). Pooled analysis of 25,839 patients with NAFLD found the prevalence of stroke to be 5.04% (95% CI, 2.74–9.09%) with an odds ratio of 1.88 (95% CI, 1.23–2.88; P=0.02) compared to non-NAFLD. The degree of steatosis assessed by ultrasonography in NAFLD was closely associated with risk of carotid atherosclerosis and stroke. Older age significantly increased the risk of developing carotid atherosclerosis, but not stroke in NAFLD.
Conclusions
This meta-analysis shows that a stepwise increment of steatosis of NAFLD can significantly increase the risk of carotid atherosclerosis and stroke development in NAFLD. Patients more than a third sufferred from carotid atherosclerosis and routine assessment of carotid atherosclerosis is quintessential in NAFLD.

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    飏 屈
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    Lidia Canillas, Agnes Soriano-Varela, Ana Rodríguez-Campello, Eva Giralt-Steinhauer, Elisa Cuadrado-Godia, Teresa Broquetas
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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  • 70 Web of Science
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Editorial

Steatotic liver disease

Nonalcoholic fatty liver disease-based risk prediction of adverse pregnancy outcomes: Ready for prime time?
Seung Mi Lee, Won Kim
Clin Mol Hepatol 2022;28(1):47-49.
Published online November 30, 2021
DOI: https://doi.org/10.3350/cmh.2021.0338

Citations

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  • Risk factor analysis and predictive model construction of lean MAFLD: a cross-sectional study of a health check-up population in China
    Ruya Zhu, Caicai Xu, Suwen Jiang, Jianping Xia, Boming Wu, Sijia Zhang, Jing Zhou, Hongliang Liu, Hongshan Li, Jianjun Lou
    European Journal of Medical Research.2025;[Epub]     CrossRef
  • GDM-BC: Non-invasive body composition dataset for intelligent prediction of Gestational Diabetes Mellitus
    Chen Zheng, Tong Qing, Mao Li, Shujuan Liao, Biru Luo, Chenwei Tang, Jiancheng Lv
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  • Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: A nationwide study
    Young Mi Jung, Seung Mi Lee, Wonyoung Wi, Min-Jeong Oh, Joong Shin Park, Geum Joon Cho, Won Kim
    JHEP Reports.2024; 6(4): 101033.     CrossRef
  • Metabolic dysfunction-associated fatty liver disease as a risk factor for adverse outcomes in subsequent pregnancy: a nationwide cohort study
    Seung Mi Lee, Geum Joon Cho, Won Young Wi, Errol R. Norwitz, Bo Kyung Koo, Jeesun Lee, Young Mi Jung, Soo Heon Kwak, Chan-Wook Park, Jong Kwan Jun, Sae Kyung Joo, Min-Jeong Oh, Won Kim, Joong Shin Park
    Hepatology International.2023; 17(2): 367.     CrossRef
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    George Agyapong, Farzaneh Dashti, Bubu A. Banini
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    Luca Marozio, Francesca Dassie, Gianluca Bertschy, Emilie M. Canuto, Gabriella Milan, Stefano Cosma, Pietro Maffei, Chiara Benedetto
    Frontiers in Genetics.2022;[Epub]     CrossRef
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  • 5 Web of Science
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Original Articles

Steatotic liver disease

Nonalcoholic fatty liver disease and early prediction of gestational diabetes mellitus using machine learning methods
Seung Mi Lee, Suhyun Hwangbo, Errol R. Norwitz, Ja Nam Koo, Ig Hwan Oh, Eun Saem Choi, Young Mi Jung, Sun Min Kim, Byoung Jae Kim, Sang Youn Kim, Gyoung Min Kim, Won Kim, Sae Kyung Joo, Sue Shin, Chan-Wook Park, Taesung Park, Joong Shin Park
Clin Mol Hepatol 2022;28(1):105-116.
Published online October 15, 2021
DOI: https://doi.org/10.3350/cmh.2021.0174
Background/Aims
To develop an early prediction model for gestational diabetes mellitus (GDM) using machine learning and to evaluate whether the inclusion of nonalcoholic fatty liver disease (NAFLD)-associated variables increases the performance of model.
Methods
This prospective cohort study evaluated pregnant women for NAFLD using ultrasound at 10–14 weeks and screened them for GDM at 24–28 weeks of gestation. The clinical variables before 14 weeks were used to develop prediction models for GDM (setting 1, conventional risk factors; setting 2, addition of new risk factors in recent guidelines; setting 3, addition of routine clinical variables; setting 4, addition of NALFD-associated variables, including the presence of NAFLD and laboratory results; and setting 5, top 11 variables identified from a stepwise variable selection method). The predictive models were constructed using machine learning methods, including logistic regression, random forest, support vector machine, and deep neural networks.
Results
Among 1,443 women, 86 (6.0%) were diagnosed with GDM. The highest performing prediction model among settings 1–4 was setting 4, which included both clinical and NAFLD-associated variables (area under the receiver operating characteristic curve [AUC] 0.563–0.697 in settings 1–3 vs. 0.740–0.781 in setting 4). Setting 5, with top 11 variables (which included NAFLD and hepatic steatosis index), showed similar predictive power to setting 4 (AUC 0.719–0.819 in setting 5, P=not significant between settings 4 and 5).
Conclusions
We developed an early prediction model for GDM using machine learning. The inclusion of NAFLDassociated variables significantly improved the performance of GDM prediction. (ClinicalTrials.gov Identifier: NCT02276144)

Citations

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  • Artificial intelligence methods in gestational diabetes mellitus prediction: A systematic literature review
    Valentina Ivanovic, Md Abu Jafar Sujan, Ole Jakob Mengshoel, Trine Moholdt
    International Journal of Medical Informatics.2026; 206: 106158.     CrossRef
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    Ting Sun, Yangyang Zhang, Chunzhi Xie, Anyi Teng, Shi Lin, Hui Zhang, Yan Li
    Frontiers in Global Women's Health.2025;[Epub]     CrossRef
  • Machine learning based model for the early detection of Gestational Diabetes Mellitus
    Hesham Zaky, Eleni Fthenou, Luma Srour, Thomas Farrell, Mohammed Bashir, Nady El Hajj, Tanvir Alam
    BMC Medical Informatics and Decision Making.2025;[Epub]     CrossRef
  • Metabolomic profiling reveals early biomarkers of gestational diabetes mellitus and associated hepatic steatosis
    Youngae Jung, Seung Mi Lee, Jinhaeng Lee, Yeonjin Kim, Woojoo Lee, Ja Nam Koo, Ig Hwan Oh, Kue Hyun Kang, Byoung Jae Kim, Sun Min Kim, Jeesun Lee, Ji Hoi Kim, Yejin Bae, Sang Youn Kim, Gyoung Min Kim, Sae Kyung Joo, Dong Hyeon Lee, Joon Ho Moon, Bo Kyung
    Cardiovascular Diabetology.2025;[Epub]     CrossRef
  • GDM-BC: Non-invasive body composition dataset for intelligent prediction of Gestational Diabetes Mellitus
    Chen Zheng, Tong Qing, Mao Li, Shujuan Liao, Biru Luo, Chenwei Tang, Jiancheng Lv
    Computers in Biology and Medicine.2025; 192: 110176.     CrossRef
  • Metabolic dysfunction–associated steatotic liver disease and pregnancy
    Monika Sarkar, Tatyana Kushner
    Journal of Clinical Investigation.2025;[Epub]     CrossRef
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    Murad Gezer, Ümit Taşdemir, Ömer Gökhan Eyisoy, Sevdenur Yiğit, Mucize Eriç Özdemir, Oya Demirci
    Acta Diabetologica.2025;[Epub]     CrossRef
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    Shaofei Su, Enjie Zhang, Shen Gao, Yue Zhang, Jianhui Liu, Shuanghua Xie, Jinghan Yu, Qiutong Zhao, Wentao Yue, Ruixia Liu, Chenghong Yin
    Clinical Medicine.2025; 25(4): 100343.     CrossRef
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    Rawan AlSaad, Ali Elhenidy, Aliya Tabassum, Nour Odeh, Eman AboArqoub, Aya Odeh, Maya AlTamimi, Alaa Abd-alrazaq, Rajat Thomas, Mohammed Bashir, Javaid Sheikh
    Journal of Diabetes Science and Technology.2025;[Epub]     CrossRef
  • What role does metabolic disfunction-associated fatty liver disease play in the metabolic landscape of pregnancy?
    Annunziata Lapolla, Maria Grazia Dalfrà
    Expert Review of Endocrinology & Metabolism.2025; : 1.     CrossRef
  • Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: A nationwide study
    Young Mi Jung, Seung Mi Lee, Wonyoung Wi, Min-Jeong Oh, Joong Shin Park, Geum Joon Cho, Won Kim
    JHEP Reports.2024; 6(4): 101033.     CrossRef
  • The early prediction of gestational diabetes mellitus by machine learning models
    Yeliz Kaya, Zafer Bütün, Özer Çelik, Ece Akça Salik, Tuğba Tahta, Arzu Altun Yavuz
    BMC Pregnancy and Childbirth.2024;[Epub]     CrossRef
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    Jong Yun Hwang
    Journal of Korean Maternal and Child Health.2024; 28(4): 153.     CrossRef
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    Brittany L. Moyce Gruber, Vernon W. Dolinsky
    Life.2023; 13(2): 301.     CrossRef
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    Ping Wu, Yi Wang, Yi Ye, Xue Yang, Yichao Huang, Yixiang Ye, Yuwei Lai, Jing Ouyang, Linjing Wu, Jianguo Xu, Jiaying Yuan, Yayi Hu, Yi-Xin Wang, Gang Liu, Da Chen, An Pan, Xiong-Fei Pan
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  • Performance Analysis and Assessment of Type 2 Diabetes Screening Scores in Patients with Non-Alcoholic Fatty Liver Disease
    Norma Latif Fitriyani, Muhammad Syafrudin, Siti Maghfirotul Ulyah, Ganjar Alfian, Syifa Latif Qolbiyani, Chuan-Kai Yang, Jongtae Rhee, Muhammad Anshari
    Mathematics.2023; 11(10): 2266.     CrossRef
  • Synergistic effect of non-alcoholic fatty liver disease and history of gestational diabetes to increase risk of type 2 diabetes
    Yoosun Cho, Yoosoo Chang, Seungho Ryu, Sarah H. Wild, Christopher D. Byrne
    European Journal of Epidemiology.2023; 38(8): 901.     CrossRef
  • Identification of influence factors in overweight population through an interpretable risk model based on machine learning: a large retrospective cohort
    Wei Lin, Songchang Shi, Huiyu Lan, Nengying Wang, Huibin Huang, Junping Wen, Gang Chen
    Endocrine.2023; 83(3): 604.     CrossRef
  • Nonalcoholic fatty liver disease-based risk prediction of adverse pregnancy outcomes: Ready for prime time?
    Seung Mi Lee, Won Kim
    Clinical and Molecular Hepatology.2022; 28(1): 47.     CrossRef
  • 11,261 View
  • 259 Download
  • 19 Web of Science
  • Crossref

Steatotic liver disease

Serum lipocalin-2 is a potential biomarker for the clinical diagnosis of nonalcoholic steatohepatitis
Gang Xu, Yu-Min Wang, Miao-Miao Ying, Sui-Dan Chen, Zong-Rui Li, Hong-Lei Ma, Ming-Hua Zheng, Jian Wu, Chunming Ding
Clin Mol Hepatol 2021;27(2):329-345.
Published online January 20, 2021
DOI: https://doi.org/10.3350/cmh.2020.0261
Background/Aims
Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis. We aimed to investigate the usefulness of a key biomarker, lipocalin-2 (LCN2), for the detection of NASH progression.
Methods
A mouse NASH model was established using a high-fat diet and a high-sugar drinking water. Gene expression profile of the NASH model was analyzed using RNA sequencing. Moreover, 360 NAFLD patients (steatosis, 83; NASH, 277), 40 healthy individuals, and 87 patients with alcoholic fatty liver disease were recruited.
Results
Inflammatory infiltration, focal necrosis in the leaflets, steatosis, and fibrosis were documented in the mouse liver. In total, 504 genes were differentially expressed in the livers of NASH mice, and showed significant functional enrichment in the inflammation-related category. Upregulated liver LCN2 was found to be significantly interactive with various interleukins and toll-like receptors. Serum LCN2 levels were significantly increased in NAFLD patients. Serum LCN2 levels were correlated with steatosis, intralobular inflammation, semiquantitative fibrosis score, and nonalcoholic fatty liver disease activity score. The area under the curve of serum LCN2 was 0.987 with a specificity of 100% and a sensitivity of 93.5% for NASH diagnosis, and 0.977 with almost the same specificity and sensitivity for steatosis.
Conclusions
LCN2 might be involved in the transition from NAFL to NASH by mediating inflammation. Serum LCN2 levels might be a novel biomarker for the diagnosis of NASH.

Citations

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  • A diet-driven metabolic dysfunction-associated steatohepatitis (MASH) mouse model resembles the corresponding human disease
    Guilherme Ribeiro Romualdo, Letícia C. Valente, Gabriel P. Bacil, Luana Riechelmann-Casarin, Antônio R. B. da Fonseca, Miguel W. Fornes, Luís F. Barbisan
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    Maiko Nagaoka, Katsuya Nagaoka, Naoto Kajitani, Kazuhiro Yoshiura, Yoko Yoshimaru, Takehisa Watanabe, Hiroko Setoyama, Noboru Fujise, Minoru Takebayashi, Yasuhito Tanaka
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    Feng Chen, Shan-Shan Wu, Chao Chen, Cheng Zhou
    World Journal of Hepatology.2024; 16(2): 177.     CrossRef
  • Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2
    Eun-Ho Lee, Jae-Ho Lee, Do-Young Kim, Young-Seung Lee, Yunju Jo, Tam Dao, Kyung Eun Kim, Dae-Kyu Song, Ji Hae Seo, Young-Kyo Seo, Je Kyung Seong, Changjong Moon, Eugene Han, Mi Kyung Kim, Seungwan Ryu, Minsang Shin, Gu Seob Roh, Hye Ra Jung, Timothy F. Os
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    Ina Bergheim, José María Moreno‐Navarrete
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  • Diagnostic and prognostic value of plasma lipocalin-2 levels in patients with metabolic dysfunction–associated steatotic liver disease
    Ahmed Mohamed ElGhandour, Nahla Mohamed Teama, Marwa Abdullah Kamal, Ehab Hassan Nashaat, Amani Mohamed Abdel Ghani, Ahmad Abbas Abdo
    Egyptian Liver Journal.2024;[Epub]     CrossRef
  • Lipocalin-2 levels increase in plasma of non-alcoholic fatty liver disease patients with metabolic syndrome
    Hirdesh Chawla, Vivek Bhosale, Ravi Misra, Satyendra Kumar Sonkar, Neera Kohli, Naseem Jamal, Shobhit Raj Vimal, Banwari Dangi, Kavita Durgapal, Shail Singh, Mahendra Pal Singh Negi, Ashim Ghatak
    International Journal of Diabetes in Developing Countries.2023; 43(1): 105.     CrossRef
  • Immune cells and their derived microRNA-enriched extracellular vesicles in nonalcoholic fatty liver diseases: Novel therapeutic targets
    Liu Yang, Yawen Hao, Joost Boeckmans, Robim M. Rodrigues, Yong He
    Pharmacology & Therapeutics.2023; 243: 108353.     CrossRef
  • Screening strategy for non-alcoholic fatty liver disease
    Saisai Zhang, Lung-Yi Mak, Man-Fung Yuen, Wai-Kay Seto
    Clinical and Molecular Hepatology.2023; 29(Suppl): S103.     CrossRef
  • Noninvasive serum biomarkers for liver fibrosis in NAFLD: current and future
    Tina Reinson, Ryan M. Buchanan, Christopher D. Byrne
    Clinical and Molecular Hepatology.2023; 29(Suppl): S157.     CrossRef
  • LCN2 contributes to the improvement of nonalcoholic steatohepatitis by 8-Cetylberberine
    Huan He, Xue Chai, Juan Li, Changsheng Li, Xinran Wu, Xiaoli Ye, Hang Ma, Xuegang Li
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    Danbi Jo, Yoon Seok Jung, Juhyun Song
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    Jiaqi Chen, Shihui Lei, Yueye Huang, Xiaojuan Zha, Lei Gu, Donglei Zhou, Jun Li, Feng Liu, Nannan Li, Lei Du, Xiu Huang, Ziwei Lin, Le Bu, Shen Qu
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    Ki Wung Chung, Ye Eun Cho, Seung-Jin Kim, Seonghwan Hwang
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    Cheng Wang, Lin Cheng, Ying Zhang, Xiaozhuo Zhao, Huijun Zhang, Yuming Shen
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  • A multi-omic landscape of steatosis-to-NASH progression
    Liping Xiang, Xiaoyan Li, Yunchen Luo, Bing Zhou, Yuejun Liu, Yao Li, Duojiao Wu, Lijing Jia, Pei-Wu Zhu, Ming-Hua Zheng, Hua Wang, Yan Lu
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  • A Scoping Review on Lipocalin-2 and Its Role in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma
    Marinela Krizanac, Paola Berenice Mass Sanchez, Ralf Weiskirchen, Anastasia Asimakopoulos
    International Journal of Molecular Sciences.2021; 22(6): 2865.     CrossRef
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    Seonghwan Hwang, Hwayoung Yun, Sungwon Moon, Ye Eun Cho, Bin Gao
    Frontiers in Endocrinology.2021;[Epub]     CrossRef
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Steatotic liver disease

Lactobacillus attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis
Na Young Lee, Min Jea Shin, Gi Soo Youn, Sang Jun Yoon, Ye Rin Choi, Hyeong Seop Kim, Haripriya Gupta, Sang Hak Han, Byoung Kook Kim, Do Yup Lee, Tae Sik Park, Hotaik Sung, Byung Yong Kim, Ki Tae Suk
Clin Mol Hepatol 2021;27(1):110-124.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0125
Background/Aims
Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice.
Methods
The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined.
Results
Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05).
Conclusions
Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.

Citations

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Reviews

Steatotic liver disease

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a major cause of liver fibrosis and cirrhosis. Accurate assessment of liver fibrosis is important for predicting disease outcomes and assessing therapeutic response in clinical practice and clinical trials. Although noninvasive tests such as transient elastography and magnetic resonance elastography are preferred where possible, histological assessment of liver fibrosis via semiquantitative scoring systems remains the current gold standard. Collagen proportionate area provides more granularity by measuring the percentage of fibrosis on a continuous scale, but is limited by the absence of architectural input. Although not yet used in routine clinical practice, advances in second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy imaging show great promise in characterising architectural features of fibrosis at the individual collagen fiber level. Quantification and calculation of different detailed variables of collagen fibers can be used to establish algorithm-based quantitative fibrosis scores (e.g., qFibrosis, q-FPs), which have been validated against fibrosis stage in NAFLD. Artificial intelligence is being explored to further refine and develop quantitative fibrosis scoring methods. SHG-microscopy shows promise as the new gold standard for the quantitative measurement of liver fibrosis. This has reaffirmed the pivotal role of the liver biopsy in fibrosis assessment in NAFLD, at least for the near-future. The ability of SHG-derived algorithms to intuitively detect subtle nuances in liver fibrosis changes over a continuous scale should be employed to redress the efficacy endpoint for fibrosis in NASH clinical trials; this approach may improve the outcomes of the trials evaluating therapeutic response to antifibrotic drugs.

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Steatotic liver disease

Precision medicine in nonalcoholic fatty liver disease: New therapeutic insights from genetics and systems biology
Silvia Sookoian, Carlos J. Pirola
Clin Mol Hepatol 2020;26(4):461-475.
Published online September 10, 2020
DOI: https://doi.org/10.3350/cmh.2020.0136
Despite more than two decades of extensive research focusing on nonalcoholic fatty liver disease (NAFLD), no approved therapy for steatohepatitis—the severe histological form of the disease—presently exists. More importantly, new drugs and small molecules with diverse molecular targets on the pathways of hepatocyte injury, inflammation, and fibrosis cannot achieve the primary efficacy endpoints. Precision medicine can potentially overcome this issue, as it is founded on extensive knowledge of the druggable genome/proteome. Hence, this review summarizes significant trends and developments in precision medicine with a particular focus on new potential therapeutic discoveries modeled via systems biology approaches. In addition, we computed and simulated the potential utility of the NAFLD polygenic risk score, which could be conceptually very advantageous not only for early disease detection but also for implementing actionable measures. Incomplete knowledge of the druggable NAFLD genome severely impedes the drug discovery process and limits the likelihood of identifying robust and safe drug candidates. Thus, we close this article with some insights into emerging disciplines, such as chemical genetics, that may accelerate accurate identification of the druggable NAFLD genome/proteome.

Citations

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Steatotic liver disease

Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH
Theresa J. Hydes, Sujan Ravi, Rohit Loomba, Meagan E. Gray
Clin Mol Hepatol 2020;26(4):383-400.
Published online July 17, 2020
DOI: https://doi.org/10.3350/cmh.2020.0067
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and affects approximately one third of adults in the United States. The disease is becoming a global epidemic as a result of the rising rates of obesity and metabolic disease. Emerging data suggest weight loss of ≥10% overall body weight is beneficial in resolving steatosis and reversing fibrosis. Prospective trials comparing various diets are limited by lack of sufficient power as well as pre- and post-treatment histopathology, and therefore no specific diet is recommended at this time. In this narrative review we examine the pathophysiology behind specific macronutrient components that can either promote or reverse NAFLD to help inform more specific dietary recommendations. Overall, the data supports reducing saturated fat, refined carbohydrates, and red and processed meats in the diet, and increasing the consumption of plant-based foods. Diets that incorporate these recommendations include plant-based diets such as the Dietary Approaches to Stop Hypertension, Mediterranean, vegetarian, and vegan diets.

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Original Article

Viral hepatitis

Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B
Yun Bin Lee, Yeonjung Ha, Young Eun Chon, Mi Na Kim, Joo Ho Lee, Hana Park, Kwang-il Kim, Soo-Hwan Kim, Kyu Sung Rim, Seong Gyu Hwang
Clin Mol Hepatol 2019;25(1):52-64.
Published online October 23, 2018
DOI: https://doi.org/10.3350/cmh.2018.0040
Background/Aims
Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake.
Methods
Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors.
Results
Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9–8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122–8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404–7.228; P=0.47).
Conclusions
Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

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Review

Steatotic liver disease

Recent research trends and updates on nonalcoholic fatty liver disease
Jeong-Ju Yoo, Won Kim, Moon Young Kim, Dae Won Jun, Sang Gyune Kim, Jong-Eun Yeon, Jin Woo Lee, Yong Kyun Cho, Sang Hoon Park, Joo Hyun Sohn, On behalf of the Korean Association for the Study of the Liver (KASL)-Korea Nonalcoholic fatty liver Study Group (KNSG)
Clin Mol Hepatol 2019;25(1):1-11.
Published online August 8, 2018
DOI: https://doi.org/10.3350/cmh.2018.0037
Nonalcoholic fatty liver disease (NAFLD), together with metabolic syndrome and obesity, has shown a rapid increase in prevalence worldwide and is emerging as a major cause of chronic liver disease and liver transplantation. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to development of end-stage liver disease and cardiometabolic disease, resulting in liver-related and non-liver–related mortality. Nonetheless, there is no standardized pharmacotherapy against NASH and many drugs are under development in ongoing clinical trials. To develop a successful anti-NASH drug, it is necessary to select an appropriate target population and treatment outcomes depending on whether the mode of action is anti-metabolic, anti-inflammatory or anti-fibrotic. Recently, innovative surrogate markers have been investigated to replace hard outcomes such as liver histology and mortality and reduce the clinical trial duration. Currently, several drugs with fast track designation are being tested in phase III clinical trials, and many other drugs have moved into phase II clinical trials. Both lean NAFLD and typical obese NAFLD have been extensively studied and genetic variants such as PNPLA3 and TM6SF2 have been identified as significant risk factors for lean NAFLD. In the near future, noninvasive biomarkers and effective targeted therapies for NASH and associated fibrosis are required to develop precision medicine and tailored therapy according to various phenotypes of NAFLD.

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Original Articles

Steatotic liver disease

Picroside II attenuates fatty acid accumulation in HepG2 cells via modulation of fatty acid uptake and synthesis
Hiteshi Dhami-Shah, Rama Vaidya, Shobha Udipi, Srividhya Raghavan, Shiny Abhijit, Viswanathan Mohan, Muthuswamy Balasubramanyam, Ashok Vaidya
Clin Mol Hepatol 2018;24(1):77-87.
Published online December 19, 2017
DOI: https://doi.org/10.3350/cmh.2017.0039
Background/Aims
Hepatic steatosis is caused by an imbalance between free fatty acids (FFAs) uptake, utilization, storage, and disposal. Understanding the molecular mechanisms involved in FFAs accumulation and its modulation could drive the development of potential therapies for Nonalcoholic fatty liver disease. The aim of the current study was to explore the effects of picroside II, a phytoactive found in Picrorhiza kurroa, on fatty acid accumulation vis-à-vis silibinin, a known hepatoprotective phytoactive from Silybum marianum.
Methods
HepG2 cells were loaded with FFAs (oleic acid:palmitic acid/2:1) for 20 hours to mimic hepatic steatosis. The FFAs concentration achieving maximum fat accumulation and minimal cytotoxicity (500 μM) was standardized. HepG2 cells were exposed to the standardized FFAs concentration with and without picroside II pretreatment.
Results
Picroside II pretreatment inhibited FFAs-induced lipid accumulation by attenuating the expression of fatty acid transport protein 5, sterol regulatory element binding protein 1 and stearoyl CoA desaturase. Preatreatment with picroside II was also found to decrease the expression of forkhead box protein O1 and phosphoenolpyruvate carboxykinase.
Conclusions
These findings suggest that picroside II effectively attenuated fatty acid accumulation by decreasing FFAs uptake and lipogenesis. Picroside II also decreased the expression of gluconeogenic genes.

Citations

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  • Elicitors Mediated Enhancement of Picrosides and Their Pathway Precursors in Dedifferentiated Cell Suspension Culture of Picrorhiza kurroa Royle ex Benth
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  • Computational dissection through network pharmacology and structure-based analysis unravels mechanistic actions of bioactive compounds in a hepatoprotective herb, Picrorhiza kurroa for the treatment of NAFLD and NASH
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  • Picrorhiza kurroa, Royle ex Benth:Traditional uses, phytopharmacology, and translational potential in therapy of fatty liver disease
    Ashwinikumar Raut, Hiteshi Dhami-Shah, Aashish Phadke, Anand Shindikar, Shobha Udipi, Jayashree Joshi, Rama Vaidya, Ashok D.B. Vaidya
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Steatotic liver disease

Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study
Gi Hyun Kim, Jung Wha Chung, Jong Ho Lee, Kyeong Sam Ok, Eun Sun Jang, Jaihwan Kim, Cheol Min Shin, Young Soo Park, Jin-Hyeok Hwang, Sook-Hyang Jeong, Nayoung Kim, Dong Ho Lee, Jin-Wook Kim
Clin Mol Hepatol 2015;21(4):379-386.
Published online December 24, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.4.379
Background/Aims

Vitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome.

Methods

A retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85).

Results

The PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P<0.01). The changes in metabolic profiles (body weight, lipid and glucose levels) did not differ between control and vitamin E groups during the study period.

Conclusions

Short-term vitamin E treatment significantly reduces ALT levels in NAFLD patients with metabolic syndrome, but metabolic profiles are not affected by vitamin E.

Citations

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    Kiwako Miyamoto, Sonoko Kondo, Takeo Kondo, Ryou Ishikawa, Ryosuke Tani, Tomoko Inoue, Keiji Matsunaga, Tetsuo Minamino, Takashi Kusaka
    World Journal of Hepatology.2025;[Epub]     CrossRef
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    Noha El-Zeiny, Rasha Hanafi, Heba Handoussa
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    Mahlet Abera, Suchith B Suresh, Aparna Malireddi, Sruthi Boddeti, Khutaija Noor, Mehwish Ansar, Iana Malasevskaia
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Steatotic liver disease

Impact of hypothyroidism on the development of non-alcoholic fatty liver disease: A 4-year retrospective cohort study
Kil Woo Lee, Ki Bae Bang, Eun Jung Rhee, Heon Ju Kwon, Mi Yeon Lee, Yong Kyun Cho
Clin Mol Hepatol 2015;21(4):372-378.
Published online December 24, 2015
DOI: https://doi.org/10.3350/cmh.2015.21.4.372
Background/Aims

Hypothyroidism is reported to contribute to the development of nonalcoholic fatty liver disease (NAFLD). We compared the risk of the development of NAFLD among three groups with different thyroid hormonal statuses (control, subclinical hypothyroidism, and overt hypothyroidism) in a 4-year retrospective cohort of Korean subjects.

Methods

Apparently healthy Korean subjects without NAFLD and aged 20-65 years were recruited (n=18,544) at health checkups performed in 2008. Annual health checkups were applied to the cohort for 4 consecutive years until December 2012. Based on their initial serum-free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels, they were classified into control, subclinical hypothyroidism (TSH >4.2 mIU/L, normal fT4), and overt hypothyroidism (TSH >4.2 mIU/L, fT4 <0.97 ng/dL) groups. NAFLD was diagnosed on the basis of ultrasonography findings.

Results

NAFLD developed in 2,348 of the 18,544 subjects, representing an overall incidence of 12.7%: 12.8%, 11.0%, 12.7% in the control, subclinical hypothyroidism, and overt hypothyroidism groups, respectively. The incidence of NAFLD did not differ significantly with the baseline thyroid hormonal status, even after multivariate adjustment (subclinical hypothyroidism group: hazard ratio [HR]=0.965, 95% confidence interval [CI]=0.814-1.143, P=0.67; overt hypothyroidism group: HR=1.255, 95% CI=0.830-1.899, P=0.28).

Conclusions

Our results suggest that the subclinical and overt types of hypothyroidism are not related to an increased incidence of NAFLD.

Citations

Citations to this article as recorded by  Crossref logo
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    Wei Hao, Lanlan Chen, Ting Li, Guoyue Lv
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    羽 龙
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Steatotic liver disease

Elevated red cell distribution width is associated with advanced fibrosis in NAFLD
Hwa Mok Kim, Bum Soo Kim, Yong Kyun Cho, Byung Ik Kim, Chong Il Sohn, Woo Kyu Jeon, Hong Joo Kim, Dong Il Park, Jung Ho Park, Kwan Joong Joo, Chang Joon Kim, Yong Sung Kim, Woon Je Heo, Won Seok Choi
Clin Mol Hepatol 2013;19(3):258-265.
Published online September 30, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.3.258
Background/Aims

The red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores.

Methods

This study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively.

Results

After adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61±0.41% (mean±SD), 12.70±0.70%, 12.77±0.62%, 12.87±0.82%, and 13.25±0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71±0.72%, 12.79±0.66%, and 13.23±1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and ≥2.67, respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and FIB-4 score of ≥1.3) increased with the RDW [BARD score: 51.1% in quartile 1 (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69 (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score.

Conclusions

Elevated RDW is independently associated with advanced fibrosis in NAFLD.

Citations

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Steatotic liver disease

The influence of waist circumference on insulin resistance and nonalcoholic fatty liver disease in apparently healthy Korean adults
Deok Yun Ju, Young Gil Choe, Yong Kyun Cho, Dong Suk Shin, Su Hyeon Yoo, Seo Hyoung Yim, Ji Yong Lee, Jung Ho Park, Hong Joo Kim, Dong Il Park, Chong Il Sohn, Woo Kyu Jeon, Byung Ik Kim
Clin Mol Hepatol 2013;19(2):140-147.
Published online June 27, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.2.140
Background/Aims

Waist circumference (WC) is a risk factor for metabolic syndrome and is related to insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to determine the association between WC and IR and NAFLD in apparently healthy Korean adults.

Methods

The volunteers included in this cross-sectional study comprised 9,159 adults (5,052 men, 4,107 women) who participated in a comprehensive health checkup program. IR was evaluated by the homeostasis model assessment of IR (HOMA-IR) and was considered to be present when the HOMA-IR score was >2. NAFLD was evaluated by ultrasound examination. Elevated alanine aminotransferase (ALT) was defined as >40 IU/L in men and >35 IU/L in women. Logistic regression was performed to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) for NAFLD, IR, and ALT according to categorized levels of WC.

Results

NAFLD was found in 2,553 (27.9%) of the participants (82.6% men, 17.4% women), while IR and elevated ALT were found in 17.2% (68.1% men, 31.9% women) and 10% (83% men, 17% women), respectively. After adjusting for confounding factors, the prevalence of NAFLD, IR, and elevated ALT was significantly associated with increases in WC quartile: highest quartile for NAFLD in men, OR=15.539, 95% CI=12.687-19.033; highest quartile for NAFLD in women, OR=48.732, 95% CI=23.918-99.288 (P<0.001); and highest quartile for IR in men, OR=17.576, 95% CI=13.283-23.255; highest quartile for IR in women, OR=11.078, 95% CI=7.813-15.708 (P<0.001); highest quartile for elevated ALT in men, OR=7.952, 95% CI=6.046-10.459; and highest quartile for elevated ALT in women, OR=8.487, 95% CI=4.679-15.395 (P<0.001).

Conclusions

WC contributes to IR and NAFLD in apparently healthy Korean adults, and thus may be an important factor in the development of IR and NAFLD.

Citations

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    Abdulrahman Ismaiel, Blal El Hosiny, Mohamed Ismaiel, Daniel-Corneliu Leucuta, Stefan-Lucian Popa, Cristina Sorina Catana, Dan L. Dumitrascu
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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
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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Steatotic liver disease

Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease
Min-Sun Kwak, Donghee Kim, Goh Eun Chung, Seung Joo Kang, Min Jung Park, Yoon Jun Kim, Jung-Hwan Yoon, Hyo-Suk Lee
Korean J Hepatol 2012;18(4):383-390.
Published online December 21, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.4.383
Background/Aims

Serum bilirubin exerts antioxidant and cytoprotective effects. In addition, elevated serum bilirubin levels are associated with a decreased risk of metabolic and cardiovascular diseases. However, few studies have evaluated whether serum bilirubin is associated with non-alcoholic fatty liver disease (NAFLD), which is closely associated with other metabolic diseases. The aim of this study was thus to elucidate the association between serum total bilirubin levels and NAFLD.

Methods

A cross-sectional study of 17,348 subjects undergoing a routine health check-up was conducted. Subjects positive for hepatitis B or hepatitis C virus, or with other hepatitis history were excluded. NAFLD was diagnosed on the basis of typical ultrasonographic findings and an alcohol consumption of less than 20 g/day.

Results

The mean age of the subjects was 49 years and 9,076 (52.3%) were men. The prevalence of NAFLD decreased steadily as the serum bilirubin level increased in both men and women (P<0.001 for both). Multivariate regression analysis adjusted for other metabolic risk factors showed that serum bilirubin level was inversely associated with the prevalence of NAFLD [odds ratio (OR)=0.88, 95% confidence interval (CI)=0.80-0.97]. Furthermore, there was an inverse, dose-dependent association between NAFLD and serum total bilirubin levels (OR=0.83, 95% CI=0.75-0.93 in the third quartile; OR=0.80, 95% CI=0.71-0.90 in the fourth quartile vs. lowest quartile, P for trend <0.001).

Conclusions

Serum bilirubin levels were found to be inversely associated with the prevalence of NAFLD independent of known metabolic risk factors. Serum bilirubin might be a protective marker for NAFLD.

Citations

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Editorials

Steatotic liver disease

Elevated serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease
Byoung Kuk Jang
Korean J Hepatol 2012;18(4):357-359.
Published online December 21, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.4.357

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Liver function tests as indicators of metabolic syndrome
Han Chu Lee
Korean J Hepatol 2011;17(1):9-11.
Published online March 21, 2011
DOI: https://doi.org/10.3350/kjhep.2011.17.1.9

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Original Article

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

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

Methods

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

Results

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

Conclusions

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

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Current status of Liver diseases in Korea: nonalcoholic fatty Liver disease
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