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"Steatosis"

Review

Hepatitis B virus (HBV) remains a major cause of chronic liver diseases, especially in the Asia-Pacific region. In recent decades, coinfection with hepatitis C virus (HCV) and coexistence with metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as significant clinical concerns among HBV-infected patients. Although global HBV vaccination programs and curative therapies for HCV have led to a marked decline in HBV/HCV coinfection, MASLD is rapidly becoming the predominant comorbidity due to the global surge in metabolic risk factors. HBV/HCV coinfection typically results in more severe liver damage, with unique challenges in antiviral treatment and risk of HBV reactivation post-HCV clearance. In contrast, HBV/MASLD overlap demonstrates complex metabolic-viral interactions that may influence viral replication, hepatitis B surface antigen seroclearance, fibrosis progression, and risk of hepatocellular carcinoma. This review critically compares the epidemiology, clinical outcomes, and management strategies of HBV patients with concurrent HCV or MASLD, while addressing current research gaps and proposing directions for future investigations.
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Original Article

Normal-weight metabolic dysfunction-associated steatotic liver disease: reclassification, characteristics, and adverse liver outcomes across diverse populations
Sherlot Juan Song, Eileen Laureal Yoon, Vincent Wai-Sun Wong, Ae Jeong Jo, Grace Lai-Hung Wong, Jimmy Che-To Lai, Dae Won Jun, Terry Cheuk-Fung Yip
Clin Mol Hepatol 2026;32(2):646-660.
Published online December 12, 2025
DOI: https://doi.org/10.3350/cmh.2025.0851
Background/Aims
Previous studies have identified a substantial degree of agreement between the non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) populations, but the same notion may not apply to normal-weight patients with a lower cardiometabolic risk burden. This study aims to investigate the cardiometabolic risk factor (CMRF) distributions between normal-weight and overweight/obese MASLD, the agreement between historical NAFLD and MASLD, and to compare the risk of liver-related events (LREs) and all-cause mortality in normal-weight versus overweight or obese MASLD.
Methods
This study included participants with steatotic liver disease (SLD) from five cohorts in China (Hong Kong), South Korea, and the United States. Participants were recruited from settings including both hospitals and communities. Individuals were classified into normal-weight and overweight/obese groups.
Results
This study included 33,793 participants with SLD from five cohorts, of whom 20,893 and 20,701 patients met the diagnosis of NAFLD and MASLD, respectively. Normal-weight patients with NAFLD demonstrated a lower CMRF distribution compared to those with overweight/obese NAFLD. In the community-based cohorts, the proportions with 0 CMRF ranged from 9.0 to 26.7% among normal-weight NAFLD patients, representing the discrepancy between MASLD and NAFLD definitions. Compared with the overweight/obese MASLD, the normalweight MASLD had increased all-cause mortality (normal-weight vs. overweight/obese, 23.44 and 13.80 per 1,000 person-years; P<0.001) but not LREs (2.81 and 2.59 per 1,000 person-years; P=0.54) in the Hong Kong Clinical Data Analysis and Reporting System cohort.
Conclusions
Normal-weight individuals with NAFLD demonstrated a lower distribution of CMRFs, resulting in the incomplete agreement between historical NAFLD and MASLD.

Citations

Citations to this article as recorded by  Crossref logo
  • Challenges in defining MASLD in lean individuals: the impact of the Fatty Liver Index on phenotypic characterisation
    Sherlot Juan Song, Yiwei Liu, Vincent Wai-Sun Wong, Terry Cheuk-Fung Yip
    Gut.2026; : gutjnl-2026-338216.     CrossRef
  • Beyond BMI: Reassessing the Prevalence of Obesity in Patients With MASLD Under the Lancet Commission Diagnostic Criteria
    Ru‐Tao Lin, Ren‐Qiang Zeng, Xu‐Ting Shen, Qin‐Mei Sun, Xin Xin, Jia‐Mei Chen, Yi‐Yang Hu, Qin Feng
    Diabetes, Obesity and Metabolism.2026;[Epub]     CrossRef
  • Metabolic Dysfunction-Associated Steatotic Liver Disease and Incretin Receptor Agonists: A Metabolic Approach to Halting Liver Disease Progression
    Ludovico Abenavoli, Anna Giulia Loricchio, Ivo Lopez, Domenico Morano, Abdulrahman Ismaiel, Dan Lucian Dumitrascu, Francesco Luzza
    Medicina.2026; 62(5): 986.     CrossRef
  • Estimated Body Fat Percentage and Triglyceride‐Glucose Index for Identifying MASLD in Lean Asian Adults: A Cross‐Sectional Analysis
    Xiang‐Ran Kong, Ya‐Li Chen, Rui Li, Lu‐Xiang Shang, Sha Sha
    The Kaohsiung Journal of Medical Sciences.2026;[Epub]     CrossRef
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  • 4 Web of Science
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Editorial

Citations

Citations to this article as recorded by  Crossref logo
  • 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
  • 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
    Clinical and Molecular Hepatology.2026; 32(1): e83.     CrossRef
  • Steatosis paradox: Unraveling pathways of suppressive effect of hepatic steatosis on hepatitis B virus
    Shang-Chin Huang, Jia-Horng Kao
    Biomedical Journal.2026; 49(3): 100969.     CrossRef
  • The Chronic Hepatitis B and Metabolic Dysfunction-Associated Steatotic Liver Disease Paradox: Friend or Foe?
    Shang-Chin Huang, Tai-Chung Tseng
    Gut and Liver.2026; 20(3): 350.     CrossRef
  • Insulin Resistance and Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients Under Antiviral Therapy
    Dong Hyun Sinn, Kyung-Ah Kim, Jung Il Lee, Geum-Youn Gwak
    Journal of Korean Medical Science.2026;[Epub]     CrossRef
  • 5,138 View
  • 49 Download
  • 2 Web of Science
  • Crossref

Correspondence

Steatotic liver disease

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Original Article

Steatotic liver disease

TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD
Baokai Sun, Xiaoqian Ding, Jie Tan, Jie Zhang, Xueru Chu, Shuimi Zhang, Shousheng Liu, Zhenzhen Zhao, Shiying Xuan, Yongning Xin, Likun Zhuang
Clin Mol Hepatol 2024;30(4):863-882.
Published online July 26, 2024
DOI: https://doi.org/10.3350/cmh.2024.0268
Backgrounds/Aims
Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood.
Methods
The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC).
Results
The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice.
Conclusions
The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Citations

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  • Association of Circadian Rhythms With the Risk of Chronic Liver Disease: Findings From a Large Prospective Study
    Rong Yang, Can Shen, Yu Jia, Yi Yao, Yiheng Zhou, Yu Cheng, Yonglang Cheng, Rui Zeng, Zhi Wan, Qian Zhao, Dongze Li, Xiaoyang Liao
    Clinical and Translational Gastroenterology.2026; 17(1): e00949.     CrossRef
  • High-protein diets and metabolic dysfunction-associated steatotic liver disease: A double-edged sword in liver health
    Hong-Yuan Yin, Qian-Hui You, Wei-Jie Zhang, Guang Ji, Yan-Qi Dang
    World Journal of Gastroenterology.2026;[Epub]     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models
    Jack Leslie, Kishore A. Krishnamurthy, Indresh K. Gopalsamy, Patricia Inacio, Meritxell Huch, Suchira Gallage, Fiona Oakley, Michele Vacca
    Nature Reviews Gastroenterology & Hepatology.2026; 23(4): 286.     CrossRef
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    Tianyang Jin, Yanni Zhao, Tingxin Xu, Yi Fang, Yaqian Cui, Wenqi Liu, Yongqiang Xiong, Jiaxi Ye, Wu Luo, Bo Hong, Guang Liang, Xiang Hu, Lijiang Huang, Yi Wang
    International Immunopharmacology.2026; 174: 116351.     CrossRef
  • Competing Cardiometabolic Pathways of Obesity and Metabolic Dysfunction–Associated Steatotic Liver Disease
    Masashi Hirooka, Teruki Miyake, Ryo Yano, Yoshiko Nakamura, Yuki Okazaki, Toyoki Shimamoto, Atsushi Yukimoto, Yasunori Yamamoto, Takao Watanabe, Osamu Yoshida, Kana Hirooka, Yoshio Tokumoto, Masanori Abe, Takeru Iwata, Yoichi Hiasa
    Gastro Hep Advances.2026; 5(4): 100882.     CrossRef
  • Using an integrative multi-omics and in vitro approach to investigate the role of tris(2-butoxyethyl) phosphate in promoting hepatic steatosis
    Gang Zhou, Xihan Gu, Xinyao Zhou, Shuai Chen, Hanyang Liu, Jing Wang
    BMJ Open Gastroenterology.2026; 13(1): e002123.     CrossRef
  • Lipid metabolism-MAFLD crosstalk: mechanisms and therapy
    Bojia Li, Shengai Piao, Yin Fu, Qiang Fu, Peiyao Qin, Weitai Kong, Yidi Ma, Zhe Zhang, Xue Fang, Xiaoyang Hu
    Frontiers in Endocrinology.2026;[Epub]     CrossRef
  • Current status survey and risk factor analysis of metabolic dysfunction-associated steatotic liver disease among adolescents in Hainan Province
    Shuo Zhou, Daya Zhang, Runyu Chen, Yan-ting Lv, Da Li, Xianfeng Huang, Fengjiao Mao, Shimei Huang, Shiju Chen, Chen Chen, Ying Mo, Yiping Du, Yuliang Huang, Fan Zeng, Qicen Yao, Feihu Bai
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    Zilong Wu, Xinyi Chen, Xiaoying Pan, Kai Luo, Zixiong Zhang, Changyu Zhou, Haibo Wang, Chuying Huang
    Frontiers in Bioscience-Landmark.2026;[Epub]     CrossRef
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    Aleksandra Klisic, Ratko Tomašević, Slavko Djuraskovic, Filiz Mercantepe, Ana Ninic
    Archives of Medical Science.2026;[Epub]     CrossRef
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    Do Han Kim, Donghyun Ko, Aijaz Ahmed, Donghee Kim
    Expert Review of Gastroenterology & Hepatology.2026; : 1.     CrossRef
  • PNPLA3 is one of the bridges between TM6SF2 E167K variant and MASLD: Correspondence to editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
    Baokai Sun, Likun Zhuang
    Clinical and Molecular Hepatology.2025; 31(1): e67.     CrossRef
  • TM6SF2 and PNPLA3: A potential dynamic duo?: Editorial on “TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD”
    Andrea Caddeo, Rosellina M. Mancina
    Clinical and Molecular Hepatology.2025; 31(1): 293.     CrossRef
  • Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study
    Chao Zhang, Tao Yang, Yuan Yu, Qian Jia, Wan-Meng Xiao, Sha Liu, Ze-Hui Yu, Cheng-Li Wen, Yan Wei, Hao Li, Mu-Han Lü
    Hereditas.2025;[Epub]     CrossRef
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    Ying Zhao, Jiali Ren, Weisan Chen, Xinchen Gao, Hongjian Yu, Xiankuan Li, Yanchao Zheng, Jinlong Yang
    Food & Function.2025; 16(8): 2926.     CrossRef
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    Mohammad Shafi Kuchay, Narendra Singh Choudhary, Bruno Ramos-Molina
    American Journal of Physiology-Cell Physiology.2025; 328(5): C1637.     CrossRef
  • Beyond obesity: lean metabolic dysfunction-associated steatohepatitis from unveiling molecular pathogenesis to therapeutic advancement
    Indrajit Bhattacharya, Deep Kumar Maity, Amit Kumar, Sampriti Sarkar, Teeshyo Bhattacharya, Amrita Sahu, Remya Sreedhar, Somasundaram Arumugam
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025; 398(10): 13647.     CrossRef
  • Liver disease trends in the Asia-Pacific region for the next 50 years
    Shuichiro Shiina, Javkhlan Maikhuu, Qing Deng, Terguunbileg Batsaikhan, Lariza Marie Canseco, Maki Tobari, Hitoshi Maruyama, Hiroaki Nagamatsu, Diana Alcantara-Payawal, Rino Gani, Yi-Hsiang Huang, Tawesak Tanwandee, Giovanni Galati, Yoon Jun Kim
    Clinical and Molecular Hepatology.2025; 31(3): 671.     CrossRef
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  • 374 Download
  • 18 Web of Science
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Letter to the Editor

Steatotic liver disease

Changing from NAFLD to MASLD: Similar cumulative incidence of reflux esophagitis between NAFLD and MASLD
Shuhei Fukunaga, Michita Mukasa, Dan Nakano, Tsubasa Tsutsumi, Takumi Kawaguchi
Clin Mol Hepatol 2024;30(1):121-123.
Published online December 4, 2023
DOI: https://doi.org/10.3350/cmh.2023.0437

Citations

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  • The impact of hepatic steatosis on epicardial adipose tissue in obese individuals
    Gül Trabzon, Fatma Öztürk Keleş, Osman Fırat Çalışkan, Şükrü Güngör, Nuriye Yarar, Ufuk Utku Güllü
    Journal of Pediatric Endocrinology and Metabolism.2026; 39(1): 46.     CrossRef
  • Metabolic dysfunction-associated steatotic liver disease and risk of four intrahepatic and extrahepatic diseases
    Yiyuan Xiao, Sihua Xu, Wenyan Hu, Jiapeng Huang, Deke Jiang, Rong Na, Zhaoqing Yin, Jingjing Zhang, Haitao Chen
    Annals of Hepatology.2025; 30(1): 101750.     CrossRef
  • Bioinformatic analysis of molecular expression patterns during the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD)
    Yuanfeng Lan, Ran Song, Duiping Feng, Junqi He
    Scientific Reports.2025;[Epub]     CrossRef
  • Pathogenic Mechanisms of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)-Associated Hepatocellular Carcinoma
    Toru Nakamura, Atsutaka Masuda, Dan Nakano, Keisuke Amano, Tomoya Sano, Masahito Nakano, Takumi Kawaguchi
    Cells.2025; 14(6): 428.     CrossRef
  • C-C motif chemokines ligand 7 contributes to metabolic dysfunction-associated steatotic liver disease by enabling redox-sensitive induction of hypermethylated in cancer 1
    Xinyue Sun, Jinge Wu, Huiqian Lv, Ben Wang, Xuelian Chen, Wenjing Ren, Xiulian Miao, Yan Guo, Xiaocen Kong, Huihui Xu, Zeqing Bao, Yong Xu, Zilong Li
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    Masahiro Sogabe, Toshiya Okahisa, Miwako Kagawa, Motoko Sei, Hiroyuki Ueda, Reiko Yokoyama, Kaizo Kagemoto, Hironori Tanaka, Yoshifumi Kida, Fumika Nakamura, Tetsu Tomonari, Koichi Okamoto, Yutaka Kawano, Hiroshi Miyamoto, Yasushi Sato, Masahiko Nakasono,
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    Tomotaka Mori, Eisuke Ozawa, Ryu Sasaki, Akane Shimakura, Kosuke Takahashi, Yoko Kido, Yasuko Kanda, Satoshi Matsuo, Kazuaki Tajima, Asami Beppu, Yasuhiko Nakao, Masanori Fukushima, Masafumi Haraguchi, Satoshi Miuma, Hisamitsu Miyaaki, Tomohiko Adachi, Su
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    Takahiko Sakaue, Hiroya Terabe, Hidetoshi Takedatsu, Takumi Kawaguchi
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  • Usefulness of health checkup‐based indices in identifying metabolic dysfunction‐associated steatotic liver disease
    Takao Miwa, Satoko Tajirika, Nanako Imamura, Miho Adachi, Ryo Horita, Tatsunori Hanai, Cheng Han Ng, Mohammad Shadab Siddiqui, Taku Fukao, Masahito Shimizu, Mayumi Yamamoto
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  • 16 Web of Science
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Editorial

Steatotic liver disease

Citations

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  • FIB‐4 Serves as a Referral Index for Coronary Artery Calcification in Patients With MASLD
    Ya‐Chin Huang, Chih‐Wen Wang, Jiun‐Chi Huang, Po‐Cheng Liang, Ming‐Lun Yeh, Yi‐Yu Chen, Yi‐Hung Lin, Tyng‐Yuan Jang, Yu‐Ju Wei, Ming‐Yen Hsieh, Chao‐Kuan Huang, Hsu‐Han Chien, Chia‐Jen Wu, Jee‐Fu Huang, Chia‐Yen Dai, Wan‐Long Chuang, Chia‐I Lin, Chung‐Fen
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    Ji Won Han
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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.

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Steatotic liver disease

Non-invasive imaging biomarkers for liver steatosis in non-alcoholic fatty liver disease: present and future
Asako Nogami, Masato Yoneda, Michihiro Iwaki, Takashi Kobayashi, Yasushi Honda, Yuji Ogawa, Kento Imajo, Satoru Saito, Atsushi Nakajima
Clin Mol Hepatol 2023;29(Suppl):S123-S135.
Published online December 12, 2022
DOI: https://doi.org/10.3350/cmh.2022.0357
Non-alcoholic fatty liver disease is currently the most common chronic liver disease, affecting up to 25% of the global population. Simple fatty liver, in which fat is deposited in the liver without fibrosis, has been regarded as a benign disease in the past, but it is now known to be prognostic. In the future, more emphasis should be placed on the quantification of liver fat. Traditionally, fatty liver has been assessed by histological evaluation, which requires an invasive examination; however, technological innovations have made it possible to evaluate fatty liver by non-invasive imaging methods, such as ultrasonography, computed tomography, and magnetic resonance imaging. In addition, quantitative as well as qualitative measurements for the detection of fatty liver have become available. In this review, we summarize the currently used qualitative evaluations of fatty liver and discuss quantitative evaluations that are expected to further develop in the future.

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Original Articles

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4
Yang Liu, Xin Zhang, Shuo Chen, Jiazhong Wang, Shuo Yu, Yiming Li, Meng Xu, Harouna Aboubacar, Junhui Li, Tao Shan, Jixin Wang, Gang Cao
Clin Mol Hepatol 2022;28(3):522-539.
Published online May 4, 2022
DOI: https://doi.org/10.3350/cmh.2022.0039
Background/Aims
Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).
Methods
Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.
Results
A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.
Conclusions
Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.

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Steatotic liver disease

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

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Liver Imaging

Drug induced liver injury

Chemotherapy induced liver abnormalities: an imaging perspective
Ankush Sharma, Roozbeh Houshyar, Priya Bhosale, Joon-Il Choi, Rajesh Gulati, Chandana Lall
Clin Mol Hepatol 2014;20(3):317-326.
Published online September 25, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.3.317

Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.

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Review

Steatotic liver disease

KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease
The Korean Association for the Study of the Liver (KASL)
Clin Mol Hepatol 2013;19(4):325-348.
Published online December 28, 2013
DOI: https://doi.org/10.3350/cmh.2013.19.4.325

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