Clinical and Molecular Hepatology

"Metabolic syndrome"

Reply to Correspondence

Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”: Shang-Chin Huang, Jia-Horng Kao; Clin Mol Hepatol 2026;32(1):e117-e118.
Published online May 13, 2025; DOI: https://doi.org/10.3350/cmh.2025.0500

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Correspondence

Correspondence to editorial 1 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”: Rui Huang, Mindie H. Nguyen; Clin Mol Hepatol 2026;32(1):e83-e84.
Published online May 8, 2025; DOI: https://doi.org/10.3350/cmh.2025.0479

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Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”
Shang-Chin Huang, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(1): e117. CrossRef

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Editorials

Type 2 diabetes as a key metabolic risk factor for adverse outcomes in nucleos(t)ide analogue-treated chronic hepatitis B: Editorial on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”: Heejoon Jang, Won Kim; Clin Mol Hepatol 2026;32(1):426-428.
Published online April 28, 2025; DOI: https://doi.org/10.3350/cmh.2025.0430

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Correspondence to editorial 2 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”
Rui Huang, Mindie H. Nguyen
Clinical and Molecular Hepatology.2026; 32(1): e85. CrossRef

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Metabolic health in antiviral era of chronic hepatitis B: Editorial on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”: Shang-Chin Huang, Jia-Horng Kao; Clin Mol Hepatol 2026;32(1):423-425.
Published online April 11, 2025; DOI: https://doi.org/10.3350/cmh.2025.0369

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Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”
Shang-Chin Huang, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(1): e117. CrossRef

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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

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Original Article

Steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments: Carlos Jose Pirola, Maria Silvina Landa, Mariano Schuman, Silvia Inés García, Adrian Salatino, Silvia Sookoian; Clin Mol Hepatol 2025;31(1):179-195.
Published online October 11, 2024; DOI: https://doi.org/10.3350/cmh.2024.0359

Background/Aims
Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis.
Methods
Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis.
Results
There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA p-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts.
Conclusions
This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.

Citations

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Sex and gender differences in metabolic dysfunction-associated liver disease
Rishitha Penmetsa, Sasha Kapil, Lisa B. VanWagner
Indian Journal of Gastroenterology.2025;[Epub] CrossRef
Animal models of lean metabolic dysfunction-associated steatotic liver disease (MASLD): bridging pathogenesis and novel drug discovery
Stavros P. Papadakos, Chara Georgiadou, Eva Kassi, Rallia-Iliana Velliou, Antonios Chatzigeorgiou
Expert Opinion on Drug Discovery.2025; 20(12): 1683. CrossRef

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Review

Steatotic liver disease

Epidemiology of metabolic dysfunction-associated steatotic liver disease: Zobair M. Younossi, Markos Kalligeros, Linda Henry; Clin Mol Hepatol 2025;31(Suppl):S32-S50.
Published online August 19, 2024; DOI: https://doi.org/10.3350/cmh.2024.0431

Abstract
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As the rates of obesity and type 2 diabetes (T2D) continue to increase globally, so does the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD). Currently, 38% of all adults and 7–14% of children and adolescents have MASLD. By 2040, the MASLD prevalence rate for adults is projected to increase to more than 55%. Although MASLD does not always develop into progressive liver disease, it has become the top indication for liver transplant in the United States for women and those with hepatocellular carcinoma (HCC). Nonetheless, the most common cause of mortality among patients with MASLD remains cardiovascular disease. In addition to liver outcomes (cirrhosis and HCC), MASLD is associated with an increased risk of developing de novo T2D, chronic kidney disease, sarcopenia, and extrahepatic cancers. Furthermore, MASLD is associated with decreased health-related quality of life, decreased work productivity, fatigue, increased healthcare resource utilization, and a substantial economic burden. Similar to other metabolic diseases, lifestyle interventions such as a heathy diet and increased physical activity remain the cornerstone of managing these patients. Although several obesity and T2D drugs are available to treat co-morbid disease, resmetirom is the only MASH-targeted medication for patients with stage 2–3 fibrosis that has approved by the Food and Drug Administration for use in the United States. This review discusses MASLD epidemiology and its related risk factors and outcomes and demonstrates that without further global initiatives, MASLD incidence could continue to increase.

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Dominika Lorek, Krzysztof Łupina, Wiktoria Bisaga, Dominik Malicki, Weronika Stępień, Laura Kumor, Jakub Janczura
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Journal of Clinical Personalized Medicine.2025; 04(02): 826. CrossRef
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Yi-Tong Li, Wei-Qing Shao, Zhen-Mei Chen, Jing Lin, Jin-Hong Chen
Clinical and Molecular Hepatology.2025; 31(2): e189. CrossRef
Prevalence of steatotic liver disease and associated fibrosis in the general population: An epidemiological survey: Letter to the editor on “Epidemiology of metabolic dysfunction-associated steatotic liver disease”
Lin Guan, Xinhe Zhang, Shanghao Liu, Xiaolong Qi, Yiling Li
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Frontiers in Nutrition.2025;[Epub] CrossRef
The Unequal Burden of Metabolic Dysfunction‐Associated Steatotic Liver Disease in 204 Countries and Territories From 1990 to 2021
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Liver International.2025;[Epub] CrossRef
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Journal of Magnetic Resonance Imaging.2025; 62(3): 800. CrossRef
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Clinical Nutrition.2025; 49: 52. CrossRef
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International Journal of Molecular Sciences.2025; 26(9): 4077. CrossRef
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Current Opinion in Clinical Nutrition & Metabolic Care.2025; 28(4): 307. CrossRef
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Food and Agricultural Immunology.2025;[Epub] CrossRef
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Frontiers in Nutrition.2025;[Epub] CrossRef
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Journal of Advanced Research.2025;[Epub] CrossRef
Association of gut microbiota dietary index with metabolic dysfunction-associated steatotic liver disease: the mediating roles of inflammation and body mass index
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Frontiers in Nutrition.2025;[Epub] CrossRef
Association of sarcopenia and physical activity on the severity of metabolic dysfunction-associated steatotic liver disease among United States adults: NHANES 2017 - 2018
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Frontiers in Aging.2025;[Epub] CrossRef
Low carbohydrate and low-calorie diets reduce liver fat and lower brain glutamate and myo-inositol levels in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Andreana P. Haley, Jack Knight-Scott, Marie Caillaud, Isabelle Gallagher, Jessica Park, Yanrong Li, Tianyu Wang, Hirofumi Tanaka, Jeffrey D. Browning
Metabolic Brain Disease.2025;[Epub] CrossRef
FGF21 reverses MASH through coordinated actions on the CNS and liver
Jesse P. Rose, Donald A. Morgan, Andrew I. Sullivan, Xiaorong Fu, Melissa Inigo-Vollmer, Shawn C. Burgess, David K. Meyerholz, Kamal Rahmouni, Matthew J. Potthoff
Cell Metabolism.2025; 37(7): 1515. CrossRef
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Vera Ciornolutchii, Abdulrahman Ismaiel, Jennifer Bogdan, Stefan‐Lucian Popa, Teodora Surdea‐Blaga, Dan L. Dumitrascu
European Journal of Clinical Investigation.2025;[Epub] CrossRef
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Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef
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Immunology.2025; 176(2): 145. CrossRef
Chronic Inflammation and Immune Dysregulation in Metabolic-Dysfunction-Associated Steatotic Liver Disease Progression: From Steatosis to Hepatocellular Carcinoma
Young-Min Jee, Jeong-Yoon Lee, Tom Ryu
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Pruritus and Fatigue in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Study of Turkish Patients From the Global NASH/MASH Registry
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Clinical and Translational Gastroenterology.2025; 16(6): e00844. CrossRef
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Bhavik Bansal, Fannie Lajeunesse-Trempe, Neil Keshvani, Carl J. Lavie, Ambarish Pandey
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Current Hepatology Reports.2025;[Epub] CrossRef
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Yong He, Yingfen Chen, Shengying Qian, Schalk van Der Merwe, Debanjan Dhar, David A. Brenner, Frank Tacke
Cellular & Molecular Immunology.2025; 22(10): 1159. CrossRef
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Frontiers in Nutrition.2025;[Epub] CrossRef
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Linda W. Moore, Elizabeth W. Brombosz, R. Mark Ghobrial
Journal of Hepatology.2025; 83(3): 625. CrossRef
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Yolande Chalmers
EMJ Hepatology.2025; : 66. CrossRef
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Current Obesity Reports.2025;[Epub] CrossRef
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Nutrients.2025; 17(13): 2189. CrossRef
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Journal of Endocrinological Investigation.2025; 48(11): 2599. CrossRef
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Diabetes, Metabolic Syndrome and Obesity.2025; Volume 18: 2019. CrossRef
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Nutrients.2025; 17(13): 2211. CrossRef
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International Journal of Molecular Sciences.2025; 26(13): 6148. CrossRef
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BMC Gastroenterology.2025;[Epub] CrossRef
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World Journal of Gastroenterology.2025;[Epub] CrossRef
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Expert Review of Gastroenterology & Hepatology.2025; : 1. CrossRef
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Gut.2025; 74(10): 1741. CrossRef
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Metabolism and Target Organ Damage.2025;[Epub] CrossRef
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World Journal of Hepatology.2025;[Epub] CrossRef
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Diabetes & Metabolism.2025; 51(6): 101698. CrossRef
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International Journal of Molecular Sciences.2025; 26(17): 8426. CrossRef
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Food Science & Nutrition.2025;[Epub] CrossRef
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Biomedicines.2025; 13(9): 2162. CrossRef
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Zhuolin Song, Volodymyr P Tryndyak, Rose A Willett, Igor P Pogribny, Ivan Rusyn, Fred A Wright
Toxicological Sciences.2025; 208(1): 155. CrossRef
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Clinical and Experimental Gastroenterology.2025; Volume 18: 191. CrossRef
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International Journal of Molecular Sciences.2025; 26(19): 9286. CrossRef
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Pharmacia.2025; 72: 1. CrossRef
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Shizhang Wei, Yuan Dong, Yanping Wang, Guohui Li, Yanling Zhao, Ruimao Zheng
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Juanita Pérez-Escobar, Aline Huerta-Álvarez, Graciela Elia Castro-Narro, María Isabel Astudillo-Delgado, Paulina Carpinteyro-Espin
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International Journal of Molecular Sciences.2025; 26(19): 9594. CrossRef
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Letter to the Editor

Steatotic liver disease

Equivalent prevalence and progression of chronic kidney disease in non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease: Hiroyuki Suzuki, Tsubasa Tsutsumi, Machiko Kawaguchi, Keisuke Amano, Takumi Kawaguchi; Clin Mol Hepatol 2024;30(4):962-964.
Published online May 20, 2024; DOI: https://doi.org/10.3350/cmh.2024.0264

Citations

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Original Article

Steatotic liver disease

Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: A systematic review and meta-analysis: Harry Crane, Guy D. Eslick, Cameron Gofton, Anjiya Shaikh, George Cholankeril, Mark Cheah, Jian-Hong Zhong, Gianluca Svegliati-Baroni, Alessandro Vitale, Beom Kyung Kim, Sang Hoon Ahn, Mi Na Kim, Simone I Strasser, Jacob George; Clin Mol Hepatol 2024;30(3):436-448.
Published online April 16, 2024; DOI: https://doi.org/10.3350/cmh.2024.0109

Background/Aims
The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows
objective
diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD).
Methods
This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC.
Results
22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC.
Conclusions
MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.

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Letter to the Editor

Steatotic liver disease

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; Clin Mol Hepatol 2024;30(2):263-265.
Published online January 18, 2024; DOI: https://doi.org/10.3350/cmh.2023.0557

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Correspondence

Steatotic liver disease

Correspondence on Letter regarding “Waiting for the changes after the adoption of steatotic liver disease”: Eileen L. Yoon, Dae Won Jun; Clin Mol Hepatol 2024;30(1):126-128.
Published online November 28, 2023; DOI: https://doi.org/10.3350/cmh.2023.0500

7,124 View
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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

Abstract
PDF

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.

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Editorial

Steatotic liver disease

Changing the nomenclature from nonalcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease is more than a change in terminology: Eileen Laurel Yoon, Dae Won Jun; Clin Mol Hepatol 2023;29(2):371-373.
Published online March 14, 2023; DOI: https://doi.org/10.3350/cmh.2023.0086

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Reviews

Chronic hepatitis B with concurrent metabolic dysfunction-associated fatty liver disease: Challenges and perspectives: Shang-Chin Huang, Chun-Jen Liu; Clin Mol Hepatol 2023;29(2):320-331.
Published online February 1, 2023; DOI: https://doi.org/10.3350/cmh.2022.0422

Abstract
PDF

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has increased among the general population and chronic hepatitis B (CHB) patients worldwide. Although fatty liver disease is a well-known risk factor for adverse liver outcomes like cirrhosis and hepatocellular carcinoma, its interactions with the hepatitis B virus (HBV) and clinical impacts seem complex. The presence of hepatic steatosis may suppress HBV viral activity, potentially leading to attenuated liver injury. In contrast, the associated co-morbidities like diabetes mellitus or obesity may increase the risk of developing adverse liver outcomes. These findings implicate that components of MAFLD may have diverse effects on the clinical manifestations of CHB. To this end, a clinical strategy is proposed for managing patients with concurrent CHB and MAFLD. This review article discusses the updated evidence regarding disease prevalence, interactions between steatosis and HBV, clinical impacts, and management strategies, aiming at optimizing holistic health care in the CHB population.

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Steatotic liver disease

Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management: Sara Battistella, Francesca D’Arcangelo, Marco Grasso, Alberto Zanetto, Martina Gambato, Giacomo Germani, Marco Senzolo, Francesco Paolo Russo, Patrizia Burra; Clin Mol Hepatol 2023;29(Suppl):S286-S301.
Published online December 28, 2022; DOI: https://doi.org/10.3350/cmh.2022.0392

Abstract
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Non-alcoholic fatty liver disease (NAFLD) is currently the fastest growing indication to liver transplantation (LT) in Western Countries, both for end stage liver disease and hepatocellular carcinoma. NAFLD/non-alcoholic steatohepatitis (NASH) is often expression of a systemic metabolic syndrome; therefore, NAFLD/NASH patients require a multidisciplinary approach for a proper pre-surgical evaluation, which is important to achieve a post-transplant outcome comparable to that of other indications to LT. NAFLD/NASH patients are also at higher risk of post-transplant cardiovascular events, diabetes, dyslipidemia, obesity, renal impairment and recurrent NASH. Lifestyle modifications, included diet and physical activity, are key to improve survival and quality of life after transplantation. A tailored immunosuppressive regimen may be proposed in selected patients. Development of new drugs for the treatment of recurrent NASH is awaited.

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Original Article

Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach: Michael H. Le, Yee Hui Yeo, Biyao Zou, Scott Barnet, Linda Henry, Ramsey Cheung, Mindie H. Nguyen; Clin Mol Hepatol 2022;28(4):841-850.
Published online September 19, 2022; DOI: https://doi.org/10.3350/cmh.2022.0239

Background/Aims
Due to increases in obesity and type 2 diabetes, the prevalence of nonalcoholic fatty liver disease (NAFLD) has also been increasing. Current forecast models may not include non-obese NAFLD. Here, we used the Bayesian approach to forecast the prevalence of NAFLD through the year 2040.
Methods
Prevalence data from 245 articles involving 2,699,627 persons were used with a hierarchical Bayesian approach to forecast the prevalence of NAFLD through 2040. Subgroup analyses were performed for age, gender, presence of metabolic syndrome, region, and smoking status. Sensitivity analysis was conducted for clinical setting and study quality.
Results
The forecasted 2040 prevalence was 55.7%, a three-fold increase since 1990 and a 43.2% increase from the 2020 prevalence of 38.9%. The estimated average yearly increase since 2020 was 2.16%. For those aged <50 years and ≥50 years, the 2040 prevalence were not significantly different (56.7% vs. 61.5%, P=0.52). There was a significant difference in 2040 prevalence by sex (males: 60% vs. 50%) but the trend was steeper for females (annual percentage change: 2.5% vs. 1.5%, P=0.025). There was no difference in trends overtime by region (P=0.48). The increase rate was significantly higher in those without metabolic syndrome (3.8% vs. 0.84%, P=0.003) and smokers (1.4% vs. 1.1%, P=0.011). There was no difference by clinical/community setting (P=0.491) or study quality (P=0.85).
Conclusion
By 2040, over half the adult population is forecasted to have NAFLD. The largest increases are expected to occur in women, smokers, and those without metabolic syndrome. Intensified efforts are needed to raise awareness of NAFLD and to determine long-term solutions addressing the driving factors of the disease.

Citations

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Editorials

Screening and prediction of nonalcoholic fatty liver disease using a peripheral insulin resistance index: Potential benefits and limitations: Soon Sun Kim, Jae Youn Cheong; Clin Mol Hepatol 2022;28(4):802-805.
Published online September 14, 2022; DOI: https://doi.org/10.3350/cmh.2022.0249

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Original Article

Steatotic liver disease

Prevalence trends of non-alcoholic fatty liver disease among young men in Korea: A Korean military population-based cross-sectional study: Jaejun Lee, Taeyun Kim, Hyun Yang, Si Hyun Bae; Clin Mol Hepatol 2022;28(2):196-206.
Published online January 13, 2022; DOI: https://doi.org/10.3350/cmh.2021.0371

Abstract
PDF

Background/Aims
Non-alcoholic fatty liver disease (NAFLD) has become a major concern in Korea since its emergence as a dominant cause of chronic liver disease. However, no study has explored its prevalence in adults under 30 years of age. Therefore, we performed a cross-sectional study to investigate the prevalence of NAFLD in Korean men in their early 20s.
Methods
We collected data of 596,359 Korean soldiers who participated in a health examination between January 2015 and July 2021. A total of 571,872 individuals were analyzed after excluding those with missing data and hepatitis B antigen positivity. Hepatic steatosis was determined using the hepatic steatosis index (HSI). Participants with HSI >36 were considered to have NAFLD.
Results
All participants were men, and the mean age was 20.9±1.3 years. Of the 571,872 participants screened, 77,020 (13.47%) were classified as having NAFLD. The prevalence of NAFLD consistently increased from 2015 to 2021 (10.66% vs. 16.44%, P<0.001). Increases from 2015 to 2021 were also noted in the prevalence of hypercholesterolemia, hyperglycemia, and hypertension (P<0.001 for all). The mean body mass index also increased from 23.3±3.0 kg/m² to 23.9±3.1 kg/m² between 2015 and 2021 (P<0.001).
Conclusions
The prevalence of NAFLD and of other metabolic dysfunctions in Korean men in their early 20s increased from 2015 to 2021.

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Review

Steatotic liver disease

From nonalcoholic fatty liver disease to metabolic-associated fatty liver disease: Big wave or ripple?: Seong Hee Kang, Yuri Cho, Soung Won Jeong, Seung Up Kim, Jin-Woo Lee, On behalf of Korean NAFLD Study Group; Clin Mol Hepatol 2021;27(2):257-269.
Published online March 22, 2021; DOI: https://doi.org/10.3350/cmh.2021.0067

Abstract
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There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.

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Original Article

Artificial intelligence, epidemiology, methodology, or others

Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome: Han Ah Lee, Jihwan Lim, Hyung Joon Joo, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Do-Sun Lim, Kwan Soo Byun, Yeon Seok Seo; Clin Mol Hepatol 2021;27(3):463-473.
Published online February 15, 2021; DOI: https://doi.org/10.3350/cmh.2020.0351

Background/Aims
Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome.
Methods
Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline.
Results
A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P<0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P<0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level <4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P<0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P<0.05).
Conclusions
Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.

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Editorial

Steatotic liver disease

Probiotics for treatment of nonalcoholic fatty liver disease: It is worth a try: Tian-Yi Ren, Xiao-Yan Li, Jian-Gao Fan; Clin Mol Hepatol 2021;27(1):83-86.
Published online December 3, 2020; DOI: https://doi.org/10.3350/cmh.2020.0298

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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

Abstract
PDF

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 Articles

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

Abstract
PDF

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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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

Abstract
PDF

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.

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Noha El-Zeiny, Rasha Hanafi, Heba Handoussa
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Vitamin E and Non-alcoholic Fatty Liver Disease: Investigating the Evidence Through a Systematic Review
Mahlet Abera, Suchith B Suresh, Aparna Malireddi, Sruthi Boddeti, Khutaija Noor, Mehwish Ansar, Iana Malasevskaia
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Editorial

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 Articles

Association of serum alanine aminotransferase and γ-glutamyltransferase levels within the reference range with metabolic syndrome and nonalcoholic fatty liver disease: Hyo Jeong Oh, Tae Hyeon Kim, Young Woo Sohn, Yong Sung Kim, Yong Reol Oh, Eun Young Cho, So Yeon Shim, Sae Ron Shin, A Lum Han, Seok Jin Yoon, Haak Cheoul Kim; Korean J Hepatol 2011;17(1):27-36.
Published online March 21, 2011; DOI: https://doi.org/10.3350/kjhep.2011.17.1.27

Abstract
PDF

Background/Aims

Nonalcoholic fatty liver disease (NAFLD) has recently been found to be a novel component of metabolic syndrome (MS), which is one of the leading causes of chronic liver disease. The serum alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) levels are suggested to affect liver fat accumulation and insulin resistance. We assessed the associations of serum ALT and GGT concentrations within the reference ranges with MS and NAFLD.

Methods

In total, 1,069 subjects enrolled at the health promotion center of Wonkwang University Hospital were divided into 4 groups according to serum ALT and GGT concentrations levels within the reference ranges. We performed biochemical tests, including liver function tests and lipid profiles, and diagnosed fatty liver by ultrasonography. Associations of ALT and GGT concentrationgrading within the reference range with fatty liver and/or MS were investigated.

Results

The presence of MS, its components, and the number of metabolic abnormalities [except for high-density lipoprotein-cholesterol (HDL-C) and fasting blood glucose] increased with the ALT level, while the presence of MS, its components, and the number of metabolic abnormalities (except for HDL-C) increased with the GGT level. The odds ratios for fatty liver and MS increased with the ALT level (P<0.001 and P=0.049, respectively) and the GGT level (P=0.044 and P=0.039, respectively).

Conclusions

Serum ALT and GGT concentrations within the reference ranges correlated with the incidence of NAFLD and MS in a dose-dependent manner. There associations need to be confirmed in large, prospective studies.

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Nonalcoholic fatty Liver disease as a risk factor of cardiovascular disease; Relation of non-alcoholic fatty Liver disease to carotid atherosclerosis: Su-Yeon Choi, M.D., Donghee Kim, M.D., Jin Hwa Kang, M.D.1, Min Jung Park, M.D., Young Sun Kim, M.D., Seon Hee Lim, M.D., Chung Hyeon Kim, M.D., Hyo-Suk Lee, M.D.2; Korean J Hepatol 2008;14(1):77-88.
Published online March 20, 2008; DOI: https://doi.org/10.3350/kjhep.2008.14.1.77

Abstract
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Background/Aims
Non-alcoholic fatty liver disease (NAFLD) is closely associated with abdominal obesity, dyslipidemia, hypertension, and Type 2 diabetes, which are all features of the metabolic syndrome. The aim of the present study was to elucidate whether NAFLD is associated with carotid atherosclerosis. Methods: The study population comprised 659 subjects without hepatitis B and C infections and who did not consume alcohol. Fatty infiltrations of liver were detected by abdominal ultrasonography, and intima-media thickness (IMT) and plaque prevalence were estimated by carotid ultrasonography. Results: The mean values of systolic and diastolic pressures, body mass index (BMI), aspartate aminotransferase, alanine aminotransferase, gamma- glutamyl transpeptidase, uric acid, total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, fasting glucose, fasting insulin, homeostasis model of assessment (HOMA) index, hemoglobin A1c, and plasminogen activator inhibitor-1 differed significantly between patients with NAFLD (n=314) and normal controls (n=345). The carotid IMT was 0.817±0.212 (mean±SD) mm in patients with NAFLD and 0.757±0.198 mm in normal controls (p<0.001). The prevalence of carotid plaques was higher in patients with NAFLD (26.4%) than in normal controls (15.9%) (p<0.001). This association persisted significantly after adjusting for age, sex, BMI, HOMA index and individual factors of metabolic syndrome by multiple logistic regression analysis. Conclusions: Patients with NAFLD are at a high risk of carotid atherosclerosis regardless of metabolic syndrome and classical cardiovascular risk factors. Therefore, the detection of NAFLD should alert to the existence of an increased cardiovascular risk. Moreover, NAFLD might be an independent risk factor for cardiovascular disease. (Korean J Hepatol 2008;14:77-88)

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Editorial

Nonalcoholic fatty Liver disease as a risk factor of cardiovascular disease: Moon Young Kim , Soon Koo Baik; Korean J Hepatol 2008;14(1):1-3.
Published online March 20, 2008; DOI: https://doi.org/10.3350/kjhep.2008.14.1.1

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Original Article

The Prevalence of Metabolic Syndrome in Patients with Nonalcoholic Fatty Liver Disease: Ki Won Moon, M.D., Joung Muk Leem, M.D., Sang Seok Bae, M.D., Ki Man Lee, M.D., Seok Hyung Kim, M.D.*, Hee Bok Chae, M.D., Seon Mee Park, M.D. and Sei Jin Youn, M.D.; Korean J Hepatol 2004;10(3):197-206.

Abstract
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Background/Aims
Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, obesity, and insulin resistance, which are the main features of metabolic syndrome. First, we examined the prevalence of metabolic syndrome among patients with NAFLD . We then compared the prevalence of metabolic syndrome in simple steatosis with that in nonalcoholic steatohepatitis (NASH). Finally, we sought to identify clinical factors associated with the stage of liver fibrosis. Methods: From November 2002 to March 2004, we enrolled consecutive 25 patients with NAFLD from patients visiting outpatient clinic. The 17 controls were healthy persons w ho visited our health promotion center. We compared the clinical and biochemical data of the NAFLD group with those of the control group. Using histologic findings, we divided NAFLD into simple steatosis and NASH. We then compared the clinical and biochemical data of the simple steatosis group with those of the NASH group. Results: Fourteen patients (14/25, 56%) had metabolic syndrome in the NAFLD group. There was no difference in the prevalence of metabolic syndrome between the simple steatosis (5/10, 50%) and the NASH group (9/15, 60%). We found significant differences in cardiovascular risk factors between the two groups, but homeostasis model assessment insulin resistance w as the only significantly different factor between the simple steatosis group and the NASH group. In addition, no difference in histological features was found between NASH with metabolic syndrome and without metabolic syndrome. Conclusions: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. We could not find any cardiovascular risk factors that could predict a severe fibrosis. (Korean J Hepatol 2004;10:197-206)

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Liver Pathology

Nonalcoholic Steatohepatitis: So-Young Jin; Korean J Hepatol 2006;12(3):455-459.

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