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"Obesity"

Review Article

Engineered nutrient-stimulated hormonal multi-agonist for precision targeting of obesity and metabolic disorders
Yun Kyung Cho, Chang Hee Jung
Received July 7, 2025  Accepted November 24, 2025  Published online November 26, 2025  
DOI: https://doi.org/10.3350/cmh.2025.0744    [Accepted]
Obesity and its related metabolic comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease, are increasingly recognized as heterogeneous and multisystemic disorders. Despite the significant benefits in glycemic control and weight loss exhibited by GLP-1 receptor agonists (GLP-1RAs), their limitations have initiated the development of engineered multi-agonist therapies targeting additional nutrient-stimulated hormonal (NUSH) pathways. Dual and triple peptide-based co-agonists combining glucagon-like peptide-1 (GLP-1) with glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, or peptide YY have demonstrated superior metabolic efficacy in preclinical and clinical studies. Tirzepatide (GLP-1/GIP dual agonist), CagriSema (GLP-1/amylin dual agonist), and retatrutide (GLP-1/GIP/glucagon triple agonist) have achieved unprecedented levels of weight loss and glycemic improvement, with certain agents also demonstrating hepatic, cardiovascular, and inflammatory benefits. Non-peptidyl oral GLP-1RAs, such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence. Multi-agonist incretin-based therapies represent a paradigm shift in the management of obesity and metabolic diseases. These agents offer broad clinical utility beyond glucose lowering by mimicking the pleiotropic hormonal responses observed after bariatric surgery. These therapies are poised to emerge as key components of precision metabolic medicine. This review article explores the mechanistic basis, pharmacological characteristics, and clinical data supporting the use of engineered NUSH-based peptide therapies for obesity and its related metabolic disorders, with particular emphasis on recent progress in the development and clinical application of dual and triple agonists.
  • 1,151 View
  • 77 Download

Original Article

Bacteroides eggerthii ameliorates metabolic dysfunction-associated steatotic liver disease through host–microbe signaling and highlights 2-hydroxyisocaproate as a potential effector
Jiyi Choi, Moon Gyeong Yoon, Se Ha Jang, Geum Ok Baek, Hyun Sun Jung, Na-Rae Lee, Choong Hwan Lee, Ji Eun Han, Jae Youn Cheong, Jung Woo Eun, Soon Sun Kim
Clin Mol Hepatol 2026;32(1):239-257.
Published online October 27, 2025
DOI: https://doi.org/10.3350/cmh.2025.0475
Background/Aims
Gut microbiome plays a pivotal role in metabolic dysfunction-associated steatotic liver disease (MASLD) pathogenesis, yet, associated functional mechanisms and host responses of specific microbial species remain insufficiently characterized. This study investigated the Bacteroides eggerthii therapeutic effects on MASLD by integrating multi-omics analysis and experimental validation in a Western diet (WD)-induced mouse model.
Methods
Candidate strains were identified using 16S rRNA gene sequencing of fecal samples from individuals with and without MASLD or obesity. B. eggerthii, a species significantly depleted in both groups, was selected for functional evaluation. Male C57BL/6J mice were fed a WD or WD supplemented with B. eggerthii (WD+B) for 12 weeks. Liver histology, serum biochemistry, fecal microbiome and metabolome profiling, and hepatic and intestinal transcriptomic analyses were performed. Anti-steatotic effects of B. eggerthii–derived metabolites were validated in vitro.
Results
Bacteroides eggerthii supplementation significantly improved liver weight, inflammation, fibrosis, and steatosis in WD+B group compared to WD alone. PICRUSt-based LEfSe analysis revealed choloylglycine hydrolase activity enrichment in gut microbiota, and strain-specific qPCR confirmed colonization in mouse colon. Integrated transcriptomic analyses revealed lipid and bile acid signaling pathway restoration, including CD36, FXR, and FGF15. Untargeted metabolomics identified elevated 2-hydroxyisocaproic acid (HICA) as a strain-derived metabolite in feces and B. eggerthii culture supernatants. In vitro, HICA significantly reduced lipid accumulation in free fatty acid-induced steatosis models.
Conclusions
Bacteroides eggerthii ameliorates MASLD via gut-liver axis modulation, including bile acid metabolism and hepatic lipid signaling. These underscore its therapeutic potential and highlight HICA as a novel microbiome-derived metabolite with anti-steatotic activity.
  • 1,952 View
  • 351 Download

Reply to Correspondence

Steatotic liver disease

Reply to correspondence on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”
Jing Zeng, Jian-Gao Fan
Clin Mol Hepatol 2025;31(2):e218-e220.
Published online February 3, 2025
DOI: https://doi.org/10.3350/cmh.2025.0070
  • 5,454 View
  • 32 Download

Letter to the Editor

What is new in the 2024 Chinese guidelines for fatty liver disease?
Rui-Xu Yang, Vincent Wai-Sun Wong, Jian-Gao Fan
Clin Mol Hepatol 2025;31(3):e239-e246.
Published online January 21, 2025
DOI: https://doi.org/10.3350/cmh.2024.1165
  • 9,454 View
  • 93 Download

Editorial

Steatotic liver disease

Revealing the importance of a multidisciplinary approach to reducing the global burden of SLD through the COVID-19 pandemic: Editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023”
Jeayeon Park, Su Jong Yu
Clin Mol Hepatol 2025;31(2):625-627.
Published online January 16, 2025
DOI: https://doi.org/10.3350/cmh.2025.0019

Citations

Citations to this article as recorded by  Crossref logo
  • The burden of steatotic liver disease before and during the COVID-19 pandemic: Correspondence to editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023”
    Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed
    Clinical and Molecular Hepatology.2025; 31(2): e183.     CrossRef
  • Reply to correspondence on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017-2023”
    Jeayeon Park, Su Jong Yu
    Clinical and Molecular Hepatology.2025; 31(2): e221.     CrossRef
  • 5,932 View
  • 25 Download
  • 2 Web of Science
  • Crossref

Correspondence

Steatotic liver disease

Correspondence to letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”
Yuri Cho, Dae Won Jun
Clin Mol Hepatol 2025;31(1):e103-e104.
Published online September 24, 2024
DOI: https://doi.org/10.3350/cmh.2024.0818
  • 4,125 View
  • 45 Download

Letter to the Editor

Steatotic liver disease

Letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”
Xiao-Song Li, Xi-Ping Shen, Hang Li
Clin Mol Hepatol 2025;31(1):e15-e16.
Published online September 12, 2024
DOI: https://doi.org/10.3350/cmh.2024.0784

Citations

Citations to this article as recorded by  Crossref logo
  • Correspondence to letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”
    Yuri Cho, Dae Won Jun
    Clinical and Molecular Hepatology.2025; 31(1): e103.     CrossRef
  • 5,026 View
  • 50 Download
  • 1 Web of Science
  • Crossref

Original Article

Steatotic liver disease

Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis
Juchul Hwang, Hyeyoung Hwang, Hyunjae Shin, Bo Hyun Kim, Seong Hee Kang, Jeong-Ju Yoo, Mi Young Choi, Dong eun Lee, Dae Won Jun, Yuri Cho
Clin Mol Hepatol 2024;30(3):561-576.
Published online June 3, 2024
DOI: https://doi.org/10.3350/cmh.2023.0384
Background/Aims
Bariatric intervention has been reported to be an effective way to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in obese individuals. The current systemic review aimed to assess the changes in MRI-determined hepatic proton density fat fraction (MRI-PDFF) and nonalcoholic fatty liver disease activity score (NAS) after bariatric surgery or intragastric balloon/gastric banding in MASLD patients with obesity.
Methods
We searched various databases including PubMed, OVID Medline, EMBASE, and Cochrane Library. Primary outcomes were the changes in intrahepatic fat on MRI-PDFF and histologic features of metabolic dysfunction-associated steatohepatitis (MASH).
Results
Thirty studies with a total of 3,134 patients were selected for meta-analysis. Bariatric intervention significantly reduced BMI (ratio of means, 0.79) and showed 72% reduction of intrahepatic fat on MRI-PDFF at 6 months after bariatric intervention (ratio of means, 0.28). Eight studies revealed that NAS was reduced by 60% at 3–6 months compared to baseline, 40% at 12–24 months, and 50% at 36–60 months. Nineteen studies revealed that the proportion of patients with steatosis decreased by 44% at 3–6 months, 37% at 12–24 months, and 29% at 36–60 months; lobular inflammation by 36% at 12–24 months and 51% at 36–60 months; ballooning degeneration by 38% at 12–24 months; significant fibrosis (≥F2) by 18% at 12–24 months and by 17% at 36–60 months after intervention.
Conclusions
Bariatric intervention significantly improved MRI-PDFF and histologic features of MASH in patients with obesity. Bariatric intervention might be the effective alternative treatment option for patients with MASLD who do not respond to lifestyle modification or medical treatment.

Citations

Citations to this article as recorded by  Crossref logo
  • Serial changes in metabolic dysfunction-associated steatotic liver disease after sleeve gastrectomy and their associations with abdominal adiposity: a prospective cohort study
    Chung-Yi Yang, Jian-Han Chen, Chung-Yen Chen, Cheng-Yi Kao, Shiu-Feng Huang, Wen-Yu Chang, Hung-Pin Tu, Jee-Fu Huang, Ming-Lung Yu, Chi-Ming Tai
    Surgery for Obesity and Related Diseases.2025; 21(5): 537.     CrossRef
  • Bariatric nutrition and evaluation of the metabolic surgical patient: Update to the 2022 Obesity Medicine Association (OMA) bariatric surgery, gastrointestinal hormones, and the microbiome clinical practice statement (CPS)
    Sue Benson-Davies, Kirsten Frederiksen, Rutuja Patel
    Obesity Pillars.2025; 13: 100154.     CrossRef
  • Letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”
    Xiao-Song Li, Xi-Ping Shen, Hang Li
    Clinical and Molecular Hepatology.2025; 31(1): e15.     CrossRef
  • Correspondence to letter to the editor on “Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis”
    Yuri Cho, Dae Won Jun
    Clinical and Molecular Hepatology.2025; 31(1): e103.     CrossRef
  • Glucagon like peptide-1 receptor agonists as a promising therapeutic option of metabolic dysfunction associated steatotic liver disease and obesity: hitting two targets with one shot
    Eda Kaya, Wing-Kin Syn, Paul Manka
    Current Opinion in Gastroenterology.2025; 41(3): 104.     CrossRef
  • Perioperative Screening for Metabolic Dysfunction Associated Steatotic Liver Disease in People Undergoing Bariatric Surgery: A Pilot Study
    David M. Williams, Thinzar Min, Andrew Beamish, Jeffrey W. Stephens
    Obesity Surgery.2025; 35(5): 1963.     CrossRef
  • Impact of Severity of Metabolism-Related Fatty Liver Disease Based on Pathologic Grading on Outcomes after Sleeve Gastrectomy
    云飞 曲
    Journal of Clinical Personalized Medicine.2025; 04(02): 826.     CrossRef
  • Cambios biométricos y metabólicos a un año de seguimiento en pacientes con obesidad e hígado graso sometidos a gastroplastia endoscópica en manga-EndoSleeve (método Apollo)
    Diego Schwarzstein, Lissette Batista, Patricia Gonçalves, Luis Yip, Leoniana Bustillos, Mar Bacardit, Josep Merlo
    Revista de la Sociedad Española de Cirugía de Obesidad y Metabólica y de la Sociedad Española para el Estudio de la Obesidad.2025;[Epub]     CrossRef
  • Therapeutic strategies targeting SREBP transcription factors: an update to 2024
    Yongdan Wang, Haitao Xiao, Lina Lai, Zuguo Zheng
    Acta Materia Medica.2025;[Epub]     CrossRef
  • Liver and obesity: a narrative review
    Amedeo Lonardo, Ralf Weiskirchen
    Exploration of Medicine.2025;[Epub]     CrossRef
  • Incretins and MASLD: at the Crossroads of Endocrine and Hepatic Disorders
    Marwin A. Farrugia, Enzo Pini, Albert Tran, Nicolas Chevalier, Rodolphe Anty, Philippe Gual
    Current Obesity Reports.2025;[Epub]     CrossRef
  • Comparative effectiveness of tirzepatide versus bariatric metabolic surgery in adults with metabolic-associated steatotic liver disease and obesity: a multi-institutional propensity score-matched study
    Jheng-Yan Wu, Yu-Min Lin, Wan-Hsuan Hsu, Ting-Hui Liu, Ya-Wen Tsai, Po-Yu Huang, Min-Hsiang Chuang, Tsung Yu, Chih-Cheng Lai
    Hepatology International.2025; 19(5): 1087.     CrossRef
  • Exploring the role of xanthine oxidase and aldehyde oxidase in metabolic dysfunction-associated steatotic liver disease (MASLD)
    Neha Gupta, Kavita Singh
    Journal of Molecular Histology.2025;[Epub]     CrossRef
  • Diabetes mellitus as a multisystem disease: understanding subtypes, complications, and the link with steatotic liver diseases in humans
    Anna Giannakogeorgou, Michael Roden, Kalliopi Pafili
    Hormones.2025;[Epub]     CrossRef
  • Duodenal mucosal ablation: An emerging therapeutic concept for metabolic dysfunction-associated fatty liver disease
    Cornelius J Fernandez, Sweekruti Jena, Vijaya Lakshmi, Joseph M Pappachan
    World Journal of Gastroenterology.2025;[Epub]     CrossRef
  • Multiparametric MRI Evaluation of Liver Fat and Iron after Glucagon-like Peptide-1 Receptor and Glucagon Receptor Dual-Agonist Treatment in a High-Fat Diet–induced Mouse Model
    Huimin Xia, Yuqin Min, Yuhua Wang, Siyu Gao, Hailing Wang, Fuhua Yan, Ruixin Liu, Jiqiu Wang, Xuejiang Gu, Tingting Bo
    Radiology.2025;[Epub]     CrossRef
  • Cirrhotic Cardiomyopathy: Bridging Hepatic and Cardiac Pathophysiology in the Modern Era
    Dragoș Lupu, Camelia Cornelia Scârneciu, Diana Țînț, Cristina Tudoran
    Journal of Clinical Medicine.2025; 14(17): 5993.     CrossRef
  • ISImatsuda as a potential predictor of metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus
    Jing Liu, Yueqiu Wang, Xinghang Zhou, Zaixin Wen, Yu Chen, Yiqiong Sun, Shuaiying Su, Weiwei Lin, Ruiting Shen, Xiaoyu Sun, Hongru Li, Xia Yu, Mingchen Zhang
    Frontiers in Medicine.2025;[Epub]     CrossRef
  • Connecting the Dots: Hepatic Steatosis as a Central Player in the Choreography of the Liver-Cardiovascular-Kidney-Metabolic Syndrome
    Richard H. Goodheart, Oyekoya T. Ayonrinde
    Heart, Lung and Circulation.2025; 34(10): 1050.     CrossRef
  • Prospective evaluation of a structured group education programme for patients with metabolic dysfunction-associated steatotic liver disease (MASLD)
    Thomas Crame, Rachel Howarth, Elizabeth Johnstone, Hollie Smith, Stuart McPherson, Kate Hallsworth
    Frontline Gastroenterology.2025; : flgastro-2025-103280.     CrossRef
  • Endoscopic Bariatric Therapies for Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanistic Insights and Metabolic Implications
    Wissam Ghusn, Mira Sridharan, Rachel Fromer, Muhammet Ozdemir, Madeleine G. Haff, Eric J. Vargas
    Biomedicines.2025; 13(10): 2437.     CrossRef
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    Herbert Tilg, Salvatore Petta, Norbert Stefan, Giovanni Targher
    JAMA.2025;[Epub]     CrossRef
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    Hao CHEN, Yang ZHOU, Haiping HAO, Jing XIONG
    Chinese Journal of Natural Medicines.2024; 22(8): 724.     CrossRef
  • Weight Loss After Sleeve Gastrectomy According to Metabolic Dysfunction-Associated Steatotic Liver Disease Stage in Patients with Obesity: A Liver Biopsy-Based Prospective Study
    José Ignacio Martínez-Montoro, Isabel Arranz-Salas, Carolina Gutiérrez-Repiso, Ana Sánchez-García, Luis Ocaña-Wilhelmi, José M. Pinazo-Bandera, Diego Fernández-García, Araceli Muñoz-Garach, Dieter Morales-García, Miren García-Cortés, Eduardo García-Fuente
    Nutrients.2024; 16(22): 3857.     CrossRef
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  • 205 Download
  • 21 Web of Science
  • Crossref

Editorial

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
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    Basile Njei, Prince Ameyaw, Yazan Al-Ajlouni, Lea-Pearl Njei, Sarpong Boateng
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    S. V. Turkina, I. A. Tyshchenko, M. N. Titarenko
    Experimental and Clinical Gastroenterology.2024; (10): 36.     CrossRef
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  • Crossref

Original Article

Steatotic liver disease

Association of Visceral Fat Obesity, Sarcopenia, and Myosteatosis with Non-Alcoholic Fatty Liver Disease without Obesity
Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe
Clin Mol Hepatol 2023;29(4):987-1001.
Published online July 5, 2023
DOI: https://doi.org/10.3350/cmh.2023.0035
Background/Aims
To investigate whether non-alcoholic fatty liver disease (NAFLD) in individuals without generalized obesity is associated with visceral fat obesity (VFO), sarcopenia, and/or myosteatosis.
Methods
This cross-sectional analysis included 14,400 individuals (7,470 men) who underwent abdominal computed tomography scans during routine health examinations. The total abdominal muscle area (TAMA) and skeletal muscle area (SMA) at the 3rd lumbar vertebral level were measured. The SMA was divided into the normal attenuation muscle area (NAMA) and low attenuation muscle area, and the NAMA/TAMA index was calculated. VFO was defined by visceral to subcutaneous fat ratio, sarcopenia by body mass index-adjusted SMA, and myosteatosis by the NAMA/TAMA index. NAFLD was diagnosed with ultrasonography.
Results
Of the 14,400 individuals, 4,748 (33.0%) had NAFLD, and the prevalence of NAFLD among non-obese individuals was 21.4%. In regression analysis, both sarcopenia (men: odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67, P<0.001; women: OR=1.59, 95% CI 1.40–1.90, P<0.001) and myosteatosis (men: OR=1.24, 95% CI 1.02–1.50, P=0,028; women: OR=1.23, 95% CI 1.04–1.46, P=0.017) were significantly associated with non-obese NAFLD after considering for VFO and other various risk factors, whereas VFO (men: OR=3.97, 95% CI 3.43–4.59 [adjusted for sarcopenia], OR 3.98, 95% CI 3.44–4.60 [adjusted for myosteatosis]; women: OR=5.42, 95% CI 4.53–6.42 [adjusted for sarcopenia], OR=5.33, 95% CI 4.51–6.31 [adjusted for myosteatosis]; all P<0.001) was strongly associated with non-obese NAFLD after adjustment with various known risk factors.
Conclusions
In addition to VFO, sarcopenia and/or myosteatosis were significantly associated with non-obese NAFLD.

Citations

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  • The Relationship Between Remnant Cholesterol and Visceral Adipose Tissue: A National Cross-Sectional Study
    Zhaoxiang Wang, Shao Zhong, Menghuan Wu, Xuejing Shao, Tian Gu, Mengjiao Xu, Qichao Yang
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    Ryohei Tanigawa, Atsushi Nakajima, Yuichiro Eguchi, Hirokazu Takahashi, Rohit Loomba, Hideki Suganami, Masaya Tanahashi, Hidenori Arai
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    Byungyoon Yun, Juyeon Oh, Heejoo Park, Jian Lee, Beom Kyung Kim, Jin‐Ha Yoon
    Liver International.2025;[Epub]     CrossRef
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    Vasily Isakov
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  • Role of estimated glucose disposal rate in predicting myosteatosis: Insights from abdominal CT analysis
    Myung Jin Kim, Yun Kyung Cho, Eun Hee Kim, Min Jung Lee, Woo Je Lee, Hong-Kyu Kim, Chang Hee Jung
    Nutrition, Metabolism and Cardiovascular Diseases.2025; 35(12): 104225.     CrossRef
  • Non-alcoholic fatty liver disease, metabolic dysfunction and sarcopenia
    G.V. Shavkuta, V.A. Gavrilyukov, V.N. Kovalenko, A.S. Zubkova, Z.M. Nalgieva
    Terapevt (General Physician).2025; (6): 60.     CrossRef
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    Liver International.2025;[Epub]     CrossRef
  • Influence of Matcha and Tea Catechins on the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)—A Review of Patient Trials and Animal Studies
    Danuta I. Kosik-Bogacka, Katarzyna Piotrowska
    Nutrients.2025; 17(15): 2532.     CrossRef
  • Associations of child-to-adult body size change with risk of hypertension and metabolic dysfunction-associated steatotic liver disease: a population-based cohort study of 226,420 individuals
    Fengyuan Tang, Wenqianzi Yang, Weijia Wu, Shengxuan Jin, Xuemei Zhen, Hengjin Dong
    BMC Public Health.2025;[Epub]     CrossRef
  • The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio is associated with early onset type 2 diabetes with NAFLD: a cross-sectional study in China
    Nini Wu, Yingqun Ni, Rilong Huang, Junhua Wang, Meimei Li, Haiying Hu, Yuanyuan Zhang, Juyi Li, Jinjun Zhang
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Editorials

Steatotic liver disease

Implications of comorbidities in nonalcoholic fatty liver disease
Sherlot Juan Song, Vincent Wai-Sun Wong
Clin Mol Hepatol 2023;29(2):384-389.
Published online March 14, 2023
DOI: https://doi.org/10.3350/cmh.2023.0066

Citations

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  • Meta‐analysis: Efficacy and safety of fibroblast growth factor 21 analogues for the treatment of non‐alcoholic steatohepatitis and non‐alcoholic steatohepatitis‐related fibrosis
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  • Bariatric intervention improves metabolic dysfunction-associated steatohepatitis in patients with obesity: A systematic review and meta-analysis
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    Clinical and Molecular Hepatology.2024; 30(3): 561.     CrossRef
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Steatotic liver disease

Non-obese or lean nonalcoholic fatty liver disease matters, but is it preventable or inevitable in light of its risk factors?
Heejoon Jang, Won Kim
Clin Mol Hepatol 2023;29(2):381-383.
Published online March 9, 2023
DOI: https://doi.org/10.3350/cmh.2023.0088

Citations

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  • Genetic and Metabolic Characteristics of Lean Nonalcoholic Fatty Liver Disease in a Korean Health Examinee Cohort
    Huiyul Park, Eileen L. Yoon, Goh Eun Chung, Eun Kyung Choe, Jung Ho Bae, Seung Ho Choi, Mimi Kim, Woochang Hwang, Hye-Lin Kim, Sun Young Yang, Dae Won Jun
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    Ioanna Aggeletopoulou, Maria Kalafateli, Efthymios P. Tsounis, Christos Triantos
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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

Citations

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  • Cross-ancestry discovery of genetic risk variants for lean metabolic dysfunction-associated steatotic liver disease
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    Eugene Han, Yong-ho Lee
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Reviews

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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Impact of diabetes, obesity, and dyslipidemia on the risk of hepatocellular carcinoma in patients with chronic liver diseases
Hwang Sik Shin, Baek Gyu Jun, Sang-Wook Yi
Clin Mol Hepatol 2022;28(4):773-789.
Published online August 8, 2022
DOI: https://doi.org/10.3350/cmh.2021.0383
Despite the increasing prevalence of metabolic disorders, the potential effects of metabolic factors on hepatocellular carcinoma (HCC) development in individuals with chronic liver diseases (CLDs) are not well understood. For a metabolic factor to be identified as a risk factor for HCC in patients with CLDs, such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, there should be a strong synergistic interaction between the carcinogenic mechanisms of the metabolic factor and the CLD itself. This review aims to comprehensively summarize the published data on the relationship between metabolic factors such as diabetes mellitus (DM), obesity, and blood lipids and the risk of HCC in patients with CLDs. DM consistently increases the risk of HCC in patients with CLD. When associated with DM, the risk of HCC seems to be highest in HCV and non-alcoholic fatty liver disease (NAFLD), followed by alcoholic liver disease (ALD) and HBV. Obesity may increase the risk of HCC. Among CLDs, the evidence is relatively consistent and clear for ALD, while clear evidence is limited in other CLDs including HBV, HCV, and NAFLD. Total cholesterol, potentially low-density lipoprotein cholesterol and triglyceride, seems to have strong inverse associations with HCC in individuals with CLDs. Despite evidence from observational studies, statins had no effect in preventing HCC in randomized controlled trials. Whether statins have a preventive effect against HCC is unclear. A better understanding and management of metabolic factors may be beneficial to reduce the risk of HCC in patients with CLDs.

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Original Article

Steatotic liver disease

Systematic review with meta-analysis: Non-alcoholic fatty liver disease and the association with pregnancy outcomes
Hydar El Jamaly, Guy D Eslick, Martin Weltman
Clin Mol Hepatol 2022;28(1):52-66.
Published online September 17, 2021
DOI: https://doi.org/10.3350/cmh.2021.0205
Background/Aims
Maternal and fetal outcomes in pregnant patients with Non-alcoholic fatty liver disease (NAFLD) have been largely unexplored. To determine the level of evidence associated with maternal and fetal outcomes in pregnant women with NAFLD.
Methods
We conducted a comprehensive literature search. The studies included pregnant patients with a previous, current or subsequent diagnosis of NAFLD. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI).
Results
Twenty-two studies, with 13,641 female NAFLD patients were reviewed. The results highlight that NAFLD patients had a statistically significant increased likelihood of baseline diabetes mellitus (OR, 6.00; 95% CI, 2.21–16.31; P<0.001; n=7), baseline Hypertension (OR, 3.75; 95% CI, 2.13–6.59; P<0.001; n=4), gestational hypertension (OR, 1.83; 95% CI, 1.03–3.26; P=0.041; n=2), and pre-eclampsia (OR, 2.43; 95% CI, 1.46–4.04; P=0.001; n=3). The odds for a past and current history of gestational diabetes mellitus were OR, 3.78; 95% CI, 2.21–6.44; P<0.001; n=5 and OR, 3.23; 95% CI, 1.97– 5.31; P<0.001; n=6, respectively. As for fetal outcomes, pregnant NAFLD patients were significantly more likely to have a premature birth (OR, 2.02; 95% CI, 1.44–2.85; P<0.001; n=4), large for gestational age birth (OR, 2.01; 95% CI, 1.72–2.37; P<0.001; n=2) or a history of prior miscarriage or abortion (OR, 1.15; 95% CI, 1.02–1.30; P=0.02; n=2). Egger’s regression revealed no evidence of publication bias (P>0.05).
Conclusions
This meta-analysis provides pooled evidence that NAFLD is associated with a substantial increase in maternal diabetic and hypertensive complications and multiple adverse fetal outcomes. This data is important for clinicians managing these patients before, during and after pregnancy.

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Editorial

Hepatic neoplasm

Metabolic disease as a risk of hepatocellular carcinoma
Naoshi Nishida
Clin Mol Hepatol 2021;27(1):87-90.
Published online December 3, 2020
DOI: https://doi.org/10.3350/cmh.2020.0302

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Original Article

Hepatic neoplasm

Obesity and the risk of primary liver cancer: A systematic review and meta-analysis
Won Sohn, Hyun Woong Lee, Sangheun Lee, Jin Hong Lim, Min Woo Lee, Chan Hyuk Park, Seung Kew Yoon
Clin Mol Hepatol 2021;27(1):157-174.
Published online November 26, 2020
DOI: https://doi.org/10.3350/cmh.2020.0176
Background/Aims
In this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer.
Methods
This study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords “obesity,” “overweight,” “body mass index (BMI),” “body weight,” “liver,” “cancer,” “hepatocellular carcinoma,” “liver cancer,” “risk,” and “mortality.” Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included.
Results
A total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancerrelated mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50–1.90, I2=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02–1.81), 1.77 (95% CI, 1.56–2.01), and 3.08 (95% CI, 1.21–7.86) for BMI >25 kg/m2, >30 kg/m2, and >35 kg/m2, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14–2.27, I2=80%).
Conclusions
High BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.

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Letter to the Editor

Steatotic liver disease

Lean non-alcoholic fatty liver disease: Is there a place for novel antidiabetics in the therapeutic management of this underappreciated “enemy”?
Dimitrios Patoulias, Michael Doumas
Clin Mol Hepatol 2020;26(4):582-583.
Published online September 25, 2020
DOI: https://doi.org/10.3350/cmh.2020.0264

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Original Article

Hepatic neoplasm

Sensitivity of ultrasound in detecting hepatocellular carcinoma in obese patients compared to explant pathology as the gold standard
Jamak Modaresi Esfeh, Kaveh Hajifathalian, Kianoush Ansari-Gilani
Clin Mol Hepatol 2020;26(1):54-59.
Published online November 15, 2019
DOI: https://doi.org/10.3350/cmh.2019.0039
Background/Aims
The American Association for the Study of Liver Diseases recommends ultrasound (US) screening for hepatocellular carcinoma (HCC) among cirrhotic patients, regardless of body mass index (BMI), every 6 months. We examined US sensitivity for diagnosis of HCC in obese patients.
Methods
Liver transplant patients data with HCC in explant was used (January 2012-December 2017). All patients underwent liver US within 3 months of diagnosis of HCC. Number/size of HCC lesions were extracted from radiologic and pathologic reports. Obesity was defined as BMI ≥30 kg/m2.
Results
One hundred sixteen patients were included. 80% were male, with mean BMI of 31 kg/m2. The most common underlying liver disease was hepatitis C virus (62%). At the time of diagnosis, median number of HCC lesions was 2 (interquartile range [IQR], 1–3), and median size of the largest lesion was 2.5 cm (IQR, 1.75–3.9). Overall sensitivity of US study for detection of HCC was 33% (95% confidence interval [CI], 29–48%). Sensitivity was 77% (95% CI, 62–93%) in patients with BMI<30 and 21% (95% CI, 11–30%) in patients with BMI≥30 (P<0.001). Size of the largest HCC lesion (P=0.290) and number of lesions (P=0.505) were not different between groups. Computed tomography (CT) scan detected HCC in 98% of the obese patients with negative US.
Conclusions
Sensitivity of US for detection of HCC is significantly lower among obese patients compared to overweight and normal weight patients. These patients may benefit from alternating between US and a different imaging modality.

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Review

Steatotic liver disease

Application of transient elastography in nonalcoholic fatty liver disease
Xinrong Zhang, Grace Lai-Hung Wong, Vincent Wai-Sun Wong
Clin Mol Hepatol 2020;26(2):128-141.
Published online November 8, 2019
DOI: https://doi.org/10.3350/cmh.2019.0001n
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Although it has become one of the leading causes of cirrhosis and hepatocellular carcinoma in the Western world, the proportion of NAFLD patients developing these complications is rather small. Therefore, current guidelines recommend noninvasive tests for the initial assessment of NAFLD. Among the available non-invasive tests, transient elastography by FibroScan® (Echosens, Paris, France) is commonly used by hepatologists in Europe and Asia, and the machine has been introduced to the United States in 2013 with rapid adoption. Transient elastography measures liver stiffness and the controlled attenuation parameter simultaneously and can serve as a one-stop examination for both liver steatosis and fibrosis. Liver stiffness measurement also correlates with clinical outcomes and can be used to select patients for varices screening. Although obesity is a common reason for measurement failures, the development of the XL probe allows successful measurements in the majority of obese patients. This article reviews the performance and limitations of transient elastography in NAFLD and highlights its clinical applications. We also discuss the reliability criteria for transient elastography examination and factors associated with false-positive liver stiffness measurements.

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Original Article

Nutritional and Metabolic liver disease

Protein and vitamin B6 intake are associated with liver steatosis assessed by transient elastography, especially in obese individuals
Yvelise Ferro, Ilaria Carè, Elisa Mazza, Francesco Provenzano, Carmela Colica, Carlo Torti, Stefano Romeo, Arturo Pujia, Tiziana Montalcini
Clin Mol Hepatol 2017;23(3):249-259.
Published online July 28, 2017
DOI: https://doi.org/10.3350/cmh.2017.0019
Background/Aims
Although the detrimental effects of several dietary components on the promotion of nonalcoholic fatty liver disease are well known, no studies have assessed the role of dietary vitamin B6. Moreover, studies on the associations between dietary components or body composition indices and liver steatosis assessed by transient elastography are rare. Our aim was to identify the nutritional factors and anthropometric parameters associated with liver steatosis.
Methods
In this cross-sectional study, we enrolled 168 individuals (35% obese) who underwent a liver steatosis assessment by Controlled Attenuation Parameter measurement and nutritional assessment.
Results
Tertiles of vitamin B6 intake were positively associated with hepatic steatosis (B=1.89, P=0.026, confidence interval [CI] 0.03-0.80) as well as with triglycerides, glucose, alanine aminotransferase (ALT), and body mass index . In obese individuals, after multivariable analysis, the Controlled Attenuation Parameter score was still associated with triglycerides, ALT, and total protein intake (B=0.56, P=0.01, CI 0.10-1.02). Participants in tertile I (low intake) had a lower Controlled Attenuation Parameter than those in tertile III (P=0.01).
Conclusions
We found a positive association between hepatic steatosis or Controlled Attenuation Parameter score and vitamin B6/total protein intake, probably related to the high intake of meat. Vitamin B6 might have a pathogenic role related to the increase of hepatic steatosis.

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Editorial

Hepatic neoplasm

Does obesity increase the risk of hepatocellular carcinoma in chronic hepatitis B patients?
Byoung Kuk Jang
Clin Mol Hepatol 2016;22(3):336-338.
Published online September 25, 2016
DOI: https://doi.org/10.3350/cmh.2016.0104

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Original Articles

Hepatic neoplasm

Obesity and hepatocellular carcinoma in patients receiving entecavir for chronic hepatitis B
Jaemin Lee, Sun Hong Yoo, Won Sohn, Hyung Woo Kim, Yong Sun Choi, Jung Ho Won, Jin Young Heo, Sang Jong Park, Young Min Park
Clin Mol Hepatol 2016;22(3):339-349.
Published online September 25, 2016
DOI: https://doi.org/10.3350/cmh.2016.0021
Background/Aims
This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment.
Methods
This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis).
Results
The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm2 (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m2 (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm2 (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602).
Conclusions
HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.

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Viral hepatitis

Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in treatment-naïve patients with chronic hepatitis B infection
Won Gil Chung, Hong Joo Kim, Young Gil Choe, Hyo Sun Seok, Chang Wook Chon, Yong Kyun Cho, Byung Ik Kim, Young Yool Koh
Korean J Hepatol 2012;18(2):195-202.
Published online June 26, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.2.195
Background/Aims

The aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV) therapy in chronic hepatitis B (CHB) patients.

Methods

The medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI) values and Alcohol Use Disorders Identification Test (AUDIT) scores were obtained at 6 months after the initiation of ETV (0.5 mg daily) treatment.

Results

A BMI of 25 kg/m2 or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3%) were obese and 17 (19.3%) were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT) normalization, and hepatitis B virus (HBV)-DNA negativity (<300 copies/mL) at 3, 6, and 12 months of treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not differ significantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was significantly lower among hazardous alcohol users (91.5% vs. 70.6%; P=0.033).

Conclusions

Obesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was significantly lower among the hazardous alcohol users.

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  • Metabolic syndrome delays HBeAg seroclearance in Chinese patients with hepatitis B
    J. C. Hsiang, G. L.‐H. Wong, H. L.‐Y. Chan, A. W.‐H. Chan, A. M.‐L. Chim, V. W.‐S. Wong
    Alimentary Pharmacology & Therapeutics.2014; 40(6): 716.     CrossRef
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Clinical Characteristics of Factory Workers with Asymptomatic Liver Function Test Abnormalities found on Serial Health Examination
Kang Mo Kim, M.D., Yoon Jun Kim, M.D., Kwang Hyuck Lee, M.D. and Domyung Paek, M.D., M.Sc., S.D.1
Korean J Hepatol 2005;11(2):144-156.
Background/Aims
The liver function tests (LFTs), such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γ-GT), have been widely used as screening tests but their low positive predictive value can cause many false positive results. To evaluate the clinical usefulness of these tests, we analyzed the serial LFT results for factory workers, and we compared the risk factors for the groups that were divided according to the serial LFT results. Methods: From June 2001 to October 2001, 1223 consecutive healthy workers in a single factory were enrolled in our study; a questionnaire, LFT and liver ultrasonography were done for all the subjects. The previous LFT results were collected from the Annual health examination survey. According to the abnormalities on the serial LFT, the participants were classified into three groups (abnormal-in-both, alternating or, normal-in-both) and the risk factors were compared among these groups using multiple logistic regression analysis. Results: The prevalence of LFT abnormality on a single test was 16.8%, but on the serial LFT, only 5% of the study participants showed consistent abnormality. The risk factors for the abnormal-in-both group, compared with the alternating group, were liver ultrasonography abnormality such as a fatty liver (odds ratio, 2.2; P=0.026) and a heavy alcohol intake (more than 210 g/week) (odds ratio, 7.2; P=0.064). HBsAg was not a significant risk factor for any of the three groups. Conclusions: In factory workers having serial LFT abnormalities, alcoholic liver disease could be the principal cause of abnormal LFT. Even if the HBsAg were positive in patients with abnormal LFT, there is the possibility of another causes for LFT abnormalities such as alcoholic liver disease and non-alcoholic steatosis or steatohepatitis. (Korean J Hepatol 2005;11:144-156)
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CMH : Clinical and Molecular Hepatology
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