Topic Editors

Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama 2360004, Japan
Department of Gastroenterology and Hepatology, Yokohama City University Hospital, Yokohama 2360004, Japan

Multiple Organ Cross-Talk and Nutrition Metabolism in the Development and Progression of NAFLD / MAFLD

Abstract submission deadline
closed (10 August 2023)
Manuscript submission deadline
closed (20 October 2023)
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Topic Information

Dear Colleagues,

The predominant discussion surrounding liver diseases has undergone a major transition from viral diseases to nonalcoholic steatohepatitis (NASH) and metabolic abnormalities of liver disease (metabolic-dysfunction-associated steatohepatitis, MAFLD), both of which are caused by lifestyle-related diseases. Therefore, novel nutritional insight into the risk factors, pathogenesis, prevention, and treatment of NAFLD and MAFLD is needed.

The liver forms a network with various organs to maintain homeostasis, including the gut–liver axis, and it has been suggested that the network with other organs may be involved in the development of NAFLD/MAFLD, their progression, and therapeutic effects.

For example, the disruption of multiorgan crosstalk in conditions, such as insulin resistance, obesity (visceral fat, adipocytokines, and lipotoxicity), changes in intestinal microflora, and sarcopenia, has been actively studied regarding its involvement in the onset and progression of NAFLD or MAFLD. The development of novel treatments and prevention strategies for NAFLD/MAFLD using specific drugs taking into account interorgan crosstalk is also expected.

In this Topic, we welcome the submission of a wide range of original papers and review articles related to NAFLD/MAFLD and other organ diseases, from basic to clinical research, especially from a nutritional perspective.

Prof. Dr. Atsushi Nakajima
Dr. Masato Yoneda
Topic Editors

Keywords

  • NAFLD
  • MAFLD
  • crosstalk
  • dysbiosis
  • comorbidity

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Gastroenterology Insights
gastroent
1.5 2.8 2009 38.4 Days CHF 1600
Journal of Clinical Medicine
jcm
3.0 5.7 2012 17.3 Days CHF 2600
Livers
livers
- 2.0 2021 26.8 Days CHF 1000
Nutrients
nutrients
4.8 9.2 2009 17.5 Days CHF 2900
Reports
reports
0.8 - 2018 18.4 Days CHF 1400

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Published Papers (14 papers)

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15 pages, 2704 KiB  
Article
Beneficial Effects of Dietary Flaxseed on Non-Alcoholic Fatty Liver Disease
by Mihir Parikh, Broderick C. Hirst, Kimberley A. O’Hara, Thane G. Maddaford, J. Alejandro Austria, Aleksandra Stamenkovic, Liping Yu, Branislav Kura, Bhavana Garg, Thomas Netticadan, Spencer D. Proctor and Grant N. Pierce
Nutrients 2024, 16(4), 466; https://doi.org/10.3390/nu16040466 - 6 Feb 2024
Cited by 1 | Viewed by 7984
Abstract
Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD. Both obese [...] Read more.
Non-alcoholic fatty liver disease (NAFLD), a significant cause of chronic liver disease, presents a considerable public health concern. Despite this, there is currently no treatment available. This study aimed to investigate dietary flaxseed in the JCR:LA-corpulent rat strain model of NAFLD. Both obese male and female rats were studied along with their lean counterparts after 12 weeks of ingestion of a control diet, or control diet with flaxseed, or high fat, high sucrose (HFHS), or HFHS plus flaxseed. Obese rats showed higher liver weight and increased levels of cholesterol, triglyceride, and saturated fatty acid, which were further elevated in rats on the HFHS diet. The HFHS diet induced a significant two-fold elevation in the plasma levels of both aspartate aminotransferase and alanine aminotransferase in the obese male and female rats. Including flaxseed in the HFHS diet significantly lowered liver weight, depressed the plasma levels of both enzymes in the obese male rats, and reduced hepatic cholesterol and triglyceride content as well as improving the fatty acid profile. In summary, including flaxseed in the diet of male and female obese rats led to an improved lipid composition in the liver and significantly reduced biomarkers of tissue injury despite consuming a HFHS chow. Full article
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3 pages, 183 KiB  
Editorial
Interactions between Multiple Organs and Nutritional Metabolism in the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease
by Masato Yoneda and Atsushi Nakajima
Nutrients 2023, 15(23), 4910; https://doi.org/10.3390/nu15234910 - 24 Nov 2023
Viewed by 952
Abstract
Steatotic liver disease (SLD) is a condition characterized by an accumulation of fat in the liver [...] Full article
18 pages, 2315 KiB  
Systematic Review
Systematic Review and Meta-Analysis: Prevalence of Non-Alcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Inflammatory Bowel Disease
by Pilar Navarro, Lucía Gutiérrez-Ramírez, Antonio Tejera-Muñoz, Ángel Arias and Alfredo J. Lucendo
Nutrients 2023, 15(21), 4507; https://doi.org/10.3390/nu15214507 - 24 Oct 2023
Cited by 3 | Viewed by 2844
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is a common concomitant condition in patients with inflammatory bowel disease (IBD). We aim to assess the magnitude of this association. Methods: We searched MEDLINE, EMBASE and Scopus libraries for the period up to February 2023 to [...] Read more.
Background: Non-alcoholic fatty liver disease (NAFLD) is a common concomitant condition in patients with inflammatory bowel disease (IBD). We aim to assess the magnitude of this association. Methods: We searched MEDLINE, EMBASE and Scopus libraries for the period up to February 2023 to identify studies reporting cohorts of IBD patients in which NALFLD was evaluated. Results: Eighty-nine studies were analyzed. The overall prevalence of NAFLD was 24.4% (95%CI, 19.3–29.8) in IBD, 20.2% (18.3–22.3) in Crohn’s disease and 18.5% (16.4–20.8) for ulcerative colitis. Higher prevalence was found in male compared to female patients, in full papers compared to abstracts, and in cross-sectional studies compared to prospective and retrospective ones. The prevalence of NAFLD in IBD has increased in studies published from 2015 onwards: 23.2% (21.5–24.9) vs. 17.8% (13.2–22.9). Diagnostic methods for NAFLD determined prevalence figures, being highest in patients assessed by controlled attenuation parameter (38.8%; 33.1–44.7) compared to ultrasonography (28.5%; 23.1–34.2) or other methods. The overall prevalence of fibrosis was 16.7% (12.2–21.7) but varied greatly according to the measurement method. Conclusion: One-quarter of patients with IBD might present with NAFLD worldwide. This proportion was higher in recent studies and in those that used current diagnostic methods. Full article
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13 pages, 7733 KiB  
Article
Alanyl-Glutamine Dipeptide Attenuates Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice by Improving Gut Microbiota Dysbiosis
by Yigang Zheng, Hanglu Ying, Jiayi Shi, Long Li and Yufen Zhao
Nutrients 2023, 15(18), 3988; https://doi.org/10.3390/nu15183988 - 14 Sep 2023
Cited by 2 | Viewed by 2293
Abstract
Non-alcoholic fatty liver disease (NAFLD) manifests as a persistent liver ailment marked by the excessive buildup of lipids within the hepatic organ accompanied by inflammatory responses and oxidative stress. Alanyl-glutamine (AG), a dipeptide comprising alanine and glutamine, is commonly employed as a nutritional [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) manifests as a persistent liver ailment marked by the excessive buildup of lipids within the hepatic organ accompanied by inflammatory responses and oxidative stress. Alanyl-glutamine (AG), a dipeptide comprising alanine and glutamine, is commonly employed as a nutritional supplement in clinical settings. This research aims to evaluate the impact of AG on NAFLD triggered by a high-fat diet (HFD), while concurrently delving into the potential mechanisms underlying its effects. The results presented herein demonstrate a notable reduction in the elevated body weight, liver mass, and liver index induced by a HFD upon AG administration. These alterations coincide with the amelioration of liver injury and the attenuation of hepatic histological advancement. Furthermore, AG treatment manifests a discernible diminution in oil-red-O-stained regions and triglyceride (TG) levels within the liver. Noteworthy alterations encompass lowered plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) concentrations, coupled with elevated high-density lipoprotein cholesterol (HDLC) concentrations. The mitigation of hepatic lipid accumulation resultant from AG administration is aligned with the downregulation of ACC1, SCD1, PPAR-γ, and CD36 expression, in conjunction with the upregulation of FXR and SHP expression. Concomitantly, AG administration leads to a reduction in the accumulation of F4/80-positive macrophages within the liver, likely attributable to the downregulated expression of MCP-1. Furthermore, AG treatment yields a decline in hepatic MDA levels and a concurrent increase in the activities of SOD and GPX. A pivotal observation underscores the effect of AG in rectifying the imbalance of gut microbiota in HFD-fed mice. Consequently, this study sheds light on the protective attributes of AG against HFD-induced NAFLD through the modulation of gut microbiota composition. Full article
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20 pages, 1553 KiB  
Review
New Insights into the Pathogenesis of Metabolic-Associated Fatty Liver Disease (MAFLD): Gut–Liver–Heart Crosstalk
by Keungmo Yang and Myeongjun Song
Nutrients 2023, 15(18), 3970; https://doi.org/10.3390/nu15183970 - 14 Sep 2023
Cited by 13 | Viewed by 4101
Abstract
Metabolism-associated fatty liver disease (MAFLD) is a multifaceted disease that involves complex interactions between various organs, including the gut and heart. It is defined by hepatic lipid accumulation and is related to metabolic dysfunction, obesity, and diabetes. Understanding the intricate interplay of the [...] Read more.
Metabolism-associated fatty liver disease (MAFLD) is a multifaceted disease that involves complex interactions between various organs, including the gut and heart. It is defined by hepatic lipid accumulation and is related to metabolic dysfunction, obesity, and diabetes. Understanding the intricate interplay of the gut–liver–heart crosstalk is crucial for unraveling the complexities of MAFLD and developing effective treatment and prevention strategies. The gut–liver crosstalk participates in the regulation of the metabolic and inflammatory processes through host–microbiome interactions. Gut microbiota have been associated with the development and progression of MAFLD, and its dysbiosis contributes to insulin resistance, inflammation, and oxidative stress. Metabolites derived from the gut microbiota enter the systemic circulation and influence both the liver and heart, resulting in the gut–liver–heart axis playing an important role in MAFLD. Furthermore, growing evidence suggests that insulin resistance, endothelial dysfunction, and systemic inflammation in MAFLD may contribute to an increased risk of cardiovascular disease (CVD). Additionally, the dysregulation of lipid metabolism in MAFLD may also lead to cardiac dysfunction and heart failure. Overall, the crosstalk between the liver and heart involves a complex interplay of molecular pathways that contribute to the development of CVD in patients with MAFLD. This review emphasizes the current understanding of the gut–liver–heart crosstalk as a foundation for optimizing patient outcomes with MAFLD. Full article
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15 pages, 1533 KiB  
Article
Change in Liver Fibrosis Associates with Progress of Diabetic Nephropathy in Patients with Nonalcoholic Fatty Liver Disease
by Yoshiko Terasaka, Hirokazu Takahashi, Kazushi Amano, Koshiro Fujisaki, Shotaro Kita, Kaori Kato, Koujin Nakayama, Yuko Yamashita, Shuji Nakamura and Keizo Anzai
Nutrients 2023, 15(14), 3248; https://doi.org/10.3390/nu15143248 - 22 Jul 2023
Cited by 1 | Viewed by 1668
Abstract
Diabetic nephropathy (DN) is a major complication of diabetes. Nonalcoholic fatty liver disease (NAFLD) is common in diabetes, and liver fibrosis is a prognostic risk factor for NAFLD. The interaction between DN and liver fibrosis in NAFLD remains unclear. In 189 patients with [...] Read more.
Diabetic nephropathy (DN) is a major complication of diabetes. Nonalcoholic fatty liver disease (NAFLD) is common in diabetes, and liver fibrosis is a prognostic risk factor for NAFLD. The interaction between DN and liver fibrosis in NAFLD remains unclear. In 189 patients with DN and NAFLD who received an education course about diabetic nephropathy, liver fibrosis was evaluated using the fibrosis-4 (FIB-4) index. The association between the outcome of DN and changes in liver fibrosis was examined. The FIB-4 index was maintained at the baseline level in patients with improved DN, while it was increased in other patients. The ΔFIB-4 index was positively correlated with changes in albuminuria and proteinuria (ρ = 0.22, p = 0.004). In a multivariate analysis, changes in albuminuria and proteinuria were associated with the ΔFIB-4 index (p = 0.002). Patients with a progressive FIB-4 index category from baseline to 5 years showed a lower event-free survival rate after 5 years than patients with an improved FIB-4 index category (p = 0.037). The outcome of DN is associated with changes in liver fibrosis in patients with diabetes, NAFLD and DN. Developing a preventive and therapeutic approach for these conditions is required. Full article
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11 pages, 1192 KiB  
Review
Maternal Weight Management to Prevent the Developmental Programming of MAFLD in Offspring of Obese Mothers
by Amanda Renae Purcell and Sarah Jean Glastras
Nutrients 2023, 15(9), 2155; https://doi.org/10.3390/nu15092155 - 30 Apr 2023
Cited by 3 | Viewed by 2241
Abstract
The global surge of obesity amongst women of reproductive age has raised concerns surrounding the health consequences for their offspring as there is a formidable link between an obesogenic maternal environment and the developmental programming of metabolic dysfunction in the offspring. Specifically, the [...] Read more.
The global surge of obesity amongst women of reproductive age has raised concerns surrounding the health consequences for their offspring as there is a formidable link between an obesogenic maternal environment and the developmental programming of metabolic dysfunction in the offspring. Specifically, the offspring of mothers with obesity have a three-fold higher risk of developing metabolic-associated fatty liver disease (MAFLD) compared to the offspring of healthy-weight mothers. Given the burgeoning burden of obesity and its comorbidities, it is essential to focus research efforts on methods to alleviate the intergenerational onset of obesity and MAFLD. This review summarizes the current research surrounding the developmental programming of MAFLD in the offspring of mothers with obesity and examines the potential for weight interventions to prevent such metabolic dysfunction in the offspring. It focuses on the benefits of pre-pregnancy interventional strategies, including dietary and exercise intervention, to ameliorate adverse liver health outcomes in the offspring. The utility and translation of these interventions for humans may be difficult for prospective mothers with obesity, thus the use of pre-pregnancy therapeutic weight loss aids, such as glucagon-like peptide-1 receptor agonists, is also discussed. Full article
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12 pages, 1203 KiB  
Article
Association of Serum Albumin Levels and Long-Term Prognosis in Patients with Biopsy-Confirmed Nonalcoholic Fatty Liver Disease
by Hirokazu Takahashi, Miwa Kawanaka, Hideki Fujii, Michihiro Iwaki, Hideki Hayashi, Hidenori Toyoda, Satoshi Oeda, Hideyuki Hyogo, Asahiro Morishita, Kensuke Munekage, Kazuhito Kawata, Tsubasa Tsutsumi, Koji Sawada, Tatsuji Maeshiro, Hiroshi Tobita, Yuichi Yoshida, Masafumi Naito, Asuka Araki, Shingo Arakaki, Takumi Kawaguchi, Hidenao Noritake, Masafumi Ono, Tsutomu Masaki, Satoshi Yasuda, Eiichi Tomita, Masato Yoneda, Akihiro Tokushige, Yoshihiro Kamada, Shinichiro Ueda, Shinichi Aishima, Yoshio Sumida, Atsushi Nakajima, Takeshi Okanoue and Japan Study Group of Nonalcoholic Fatty Liver Disease (JSG-NAFLD)add Show full author list remove Hide full author list
Nutrients 2023, 15(9), 2014; https://doi.org/10.3390/nu15092014 - 22 Apr 2023
Cited by 9 | Viewed by 2731
Abstract
The relationship between baseline serum albumin level and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. This is a sub-analysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) study. The main outcomes were: death or orthotopic liver transplantation [...] Read more.
The relationship between baseline serum albumin level and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) remains unknown. This is a sub-analysis of the CLIONE (Clinical Outcome Nonalcoholic Fatty Liver Disease) study. The main outcomes were: death or orthotopic liver transplantation (OLT), liver-related death, and liver-related events (hepatocellular carcinoma [HCC], decompensated cirrhosis, and gastroesophageal varices/bleeding). 1383 Japanese patients with biopsy-confirmed NAFLD were analyzed. They were divided into 3 groups based on serum albumin: high (>4.0 g/dL), intermediate (3.5–4.0 g/dL), and low (<3.5 g/dL). Unadjusted hazard ratio [HR] of the intermediate albumin group, compared with the high albumin group, were 3.6 for death or OLT, 11.2 for liver-related death, 4.6 for HCC, 8.2 for decompensated cirrhosis, and 6.2 for gastroesophageal varices (all risks were statistically significant). After adjusting confounding factors, albumin remained significantly associated with death or OLT (intermediate vs. high albumin group: HR 3.06, 95% confidence interval [CI] 1.59–5.91, p < 0.001; low vs. high albumin group: HR 22.9, 95% CI 8.21–63.9, p < 0.001). Among biopsy-confirmed NAFLD patients, those with intermediate or low serum albumin had a significantly higher risk of death or OLT than those with high serum albumin. Full article
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14 pages, 3635 KiB  
Article
Proteomic Analysis Reveals Changes in Tight Junctions in the Small Intestinal Epithelium of Mice Fed a High-Fat Diet
by Hisanori Muto, Takashi Honda, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Takanori Ito, Norihiro Imai, Yoji Ishizu, Keiko Maeda, Tetsuya Ishikawa, Shungo Adachi, Chikara Sato, Noriko M. Tsuji, Masatoshi Ishigami, Mitsuhiro Fujishiro and Hiroki Kawashima
Nutrients 2023, 15(6), 1473; https://doi.org/10.3390/nu15061473 - 19 Mar 2023
Cited by 3 | Viewed by 2612
Abstract
The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a [...] Read more.
The impact of a high-fat diet (HFD) on intestinal permeability has been well established. When bacteria and their metabolites from the intestinal tract flow into the portal vein, inflammation in the liver is triggered. However, the exact mechanism behind the development of a leaky gut caused by an HFD is unclear. In this study, we investigated the mechanism underlying the leaky gut related to an HFD. C57BL/6J mice were fed an HFD or control diet for 24 weeks, and their small intestine epithelial cells (IECs) were analyzed using deep quantitative proteomics. A significant increase in fat accumulation in the liver and a trend toward increased intestinal permeability were observed in the HFD group compared to the control group. Proteomics analysis of the upper small intestine epithelial cells identified 3684 proteins, of which 1032 were differentially expressed proteins (DEPs). Functional analysis of DEPs showed significant enrichment of proteins related to endocytosis, protein transport, and tight junctions (TJ). Expression of Cldn7 was inversely correlated with intestinal barrier function and strongly correlated with that of Epcam. This study will make important foundational contributions by providing a comprehensive depiction of protein expression in IECs affected by HFD, including an indication that the Epcam/Cldn7 complex plays a role in leaky gut. Full article
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11 pages, 952 KiB  
Review
Involvement of Periodontal Disease in the Pathogenesis and Exacerbation of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis: A Review
by Takashi Kobayashi, Michihiro Iwaki, Asako Nogami, Yasushi Honda, Yuji Ogawa, Kento Imajo, Satoru Saito, Atsushi Nakajima and Masato Yoneda
Nutrients 2023, 15(5), 1269; https://doi.org/10.3390/nu15051269 - 3 Mar 2023
Cited by 4 | Viewed by 2629
Abstract
The increasing incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), along with global lifestyle changes, requires further in-depth research to elucidate the mechanisms and develop new treatment strategies. In addition, the number of patients with periodontal disease has increased recently, [...] Read more.
The increasing incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), along with global lifestyle changes, requires further in-depth research to elucidate the mechanisms and develop new treatment strategies. In addition, the number of patients with periodontal disease has increased recently, suggesting that periodontal disease is sometimes associated with systemic conditions. In this review, we summarize recent studies linking periodontal disease and NAFLD, the concept of the mouth–gut–liver axis, oral and intestinal microbiota, and liver disease. We suggest new research directions toward a detailed mechanistic understanding and novel targets for treatment and prevention. Forty years have passed since the concepts of NAFLD and NASH were first proposed. however, no effective prevention or treatment has been established. We also found that the pathogenesis of NAFLD/NASH is not limited to liver-related diseases but has been reported to be associated with various systemic diseases and an increasing number of causes of death. In addition, changes in the intestinal microbiota have been shown to be a risk factor for periodontal diseases, such as atherosclerosis, diabetes, rheumatoid arthritis, nonalcoholic fatty liver disease, and obesity. Full article
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12 pages, 453 KiB  
Article
Severity of Liver Fibrosis Is Associated with the Japanese Diet Pattern and Skeletal Muscle Mass in Patients with Nonalcoholic Fatty Liver Disease
by Yoshinari Matsumoto, Hideki Fujii, Mika Harima, Haruna Okamura, Yoshimi Yukawa-Muto, Naoshi Odagiri, Hiroyuki Motoyama, Kohei Kotani, Ritsuzo Kozuka, Etsushi Kawamura, Atsushi Hagihara, Sawako Uchida-Kobayashi, Masaru Enomoto, Yoko Yasui, Daiki Habu and Norifumi Kawada
Nutrients 2023, 15(5), 1175; https://doi.org/10.3390/nu15051175 - 26 Feb 2023
Cited by 7 | Viewed by 6892
Abstract
It is not fully clear as to which dietary patterns are associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in Asia. We conducted a cross-sectional study of 136 consecutively recruited patients with NAFLD (49% female, median age 60 years). Severity of [...] Read more.
It is not fully clear as to which dietary patterns are associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in Asia. We conducted a cross-sectional study of 136 consecutively recruited patients with NAFLD (49% female, median age 60 years). Severity of liver fibrosis was assessed using the Agile 3+ score, a recently proposed system based on vibration-controlled transient elastography. Dietary status was assessed using the 12-component modified Japanese diet pattern index (mJDI12). Skeletal muscle mass was assessed by bioelectrical impedance. Factors associated with intermediate–high-risk Agile 3+ scores and skeletal muscle mass (75th percentile or higher) were analyzed by multivariable logistic regression. After adjustment for confounders, such as age and sex, the mJDI12 (OR: 0.77; 95% CI: 0.61, 0.99) and skeletal muscle mass (75th percentile or higher) (OR: 0.23; 95% CI: 0.07, 0.77) were significantly associated with intermediate–high-risk Agile 3+ scores. Soybeans and soybean foods were significantly associated with skeletal muscle mass (75th percentile or higher) (OR: 1.02; 95% CI: 1.00, 1.04). In conclusion, the Japanese diet pattern was associated with the severity of liver fibrosis in Japanese patients with NAFLD. Skeletal muscle mass was also associated with the severity of liver fibrosis, and intake of soybeans and soybean foods. Full article
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15 pages, 1707 KiB  
Review
The Inter-Organ Crosstalk Reveals an Inevitable Link between MAFLD and Extrahepatic Diseases
by Tsubasa Tsutsumi, Dan Nakano, Ryuki Hashida, Tomoya Sano, Machiko Kawaguchi, Keisuke Amano and Takumi Kawaguchi
Nutrients 2023, 15(5), 1123; https://doi.org/10.3390/nu15051123 - 23 Feb 2023
Cited by 8 | Viewed by 3511
Abstract
Fatty liver is known to be associated with extra-hepatic diseases including atherosclerotic cardiovascular disease and extra-hepatic cancers, which affect the prognosis and quality of life of the patients. The inter-organ crosstalk is mediated by metabolic abnormalities such as insulin resistance and visceral adiposity. [...] Read more.
Fatty liver is known to be associated with extra-hepatic diseases including atherosclerotic cardiovascular disease and extra-hepatic cancers, which affect the prognosis and quality of life of the patients. The inter-organ crosstalk is mediated by metabolic abnormalities such as insulin resistance and visceral adiposity. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed as a new definition for fatty liver. MAFLD is characterized by the inclusion criteria of metabolic abnormality. Therefore, MAFLD is expected to identify patients at high risk of extra-hepatic complications. In this review, we focus on the relationships between MAFLD and multi-organ diseases. We also describe the pathogenic mechanisms of the inter-organ crosstalk. Full article
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13 pages, 464 KiB  
Review
Impact of Sarcopenia on Non-Alcoholic Fatty Liver Disease
by Michihiro Iwaki, Takashi Kobayashi, Asako Nogami, Satoru Saito, Atsushi Nakajima and Masato Yoneda
Nutrients 2023, 15(4), 891; https://doi.org/10.3390/nu15040891 - 10 Feb 2023
Cited by 24 | Viewed by 4719
Abstract
With the increasing incidence of non-alcoholic fatty liver disease (NAFLD) and the aging of the population, sarcopenia is attracting attention as one of the pathological conditions involved in the development and progression of NAFLD. In NAFLD, sarcopenia is closely associated with insulin resistance [...] Read more.
With the increasing incidence of non-alcoholic fatty liver disease (NAFLD) and the aging of the population, sarcopenia is attracting attention as one of the pathological conditions involved in the development and progression of NAFLD. In NAFLD, sarcopenia is closely associated with insulin resistance and results from the atrophy of skeletal muscle, an insulin target organ. In addition, inflammatory cytokines that promote skeletal muscle protein breakdown, low adiponectin levels leading to decreased insulin sensitivity, and hyperleptinemia are also involved in NAFLD pathogenesis. The presence of sarcopenia is a prognostic factor and increases the risk of mortality in patients with cirrhosis and post-treatment liver cancer. Sarcopenia, the presence of which mainly occurs due to decreased muscle mass, combined with increased visceral fat, can lead to sarcopenia-associated obesity, which increases the risk of NASH, liver fibrosis, and cardiovascular disease. In order to treat sarcopenia, it is necessary to properly evaluate sarcopenia status. Patients with high BMI, as in sarcopenic obesity, may improve with caloric restriction. However, inadequate oral intake may lead to further loss of muscle mass. Aerobic and resistance exercise should also be used appropriately. Full article
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13 pages, 2583 KiB  
Article
The FIB-4 Index Predicts the Development of Liver-Related Events, Extrahepatic Cancers, and Coronary Vascular Disease in Patients with NAFLD
by Yoshihiro Kamada, Kensuke Munekage, Takashi Nakahara, Hideki Fujii, Yoshiyuki Sawai, Yoshinori Doi, Hideyuki Hyogo, Yoshio Sumida, Yasuharu Imai, Eiji Miyoshi and Masafumi Ono
Nutrients 2023, 15(1), 66; https://doi.org/10.3390/nu15010066 - 23 Dec 2022
Cited by 9 | Viewed by 2798
Abstract
The prognosis of nonalcoholic fatty liver disease (NAFLD) patients depends on liver-related events (LREs), extrahepatic cancers, and major adverse cardiovascular events (MACEs). The fibrosis-4 (FIB-4) index is one of the most reliable and useful predictors of the degree of liver fibrosis. Recent studies [...] Read more.
The prognosis of nonalcoholic fatty liver disease (NAFLD) patients depends on liver-related events (LREs), extrahepatic cancers, and major adverse cardiovascular events (MACEs). The fibrosis-4 (FIB-4) index is one of the most reliable and useful predictors of the degree of liver fibrosis. Recent studies have reported that the FIB-4 index is also useful for predicting LREs and MACEs in NAFLD patients. In the present study, we investigated the prognostic value of the FIB-4 index in NAFLD patients. A total of 506 biopsy-confirmed NAFLD patients from six hepatology centers in Japan from 2002 to 2013 were enrolled in this study. Of these NAFLD patients, 353 were available for more than 100 days of follow-up and did not exhibit events (LREs, extrahepatic cancers, MACEs) at the time of entry. The mean follow-up duration of all the subjects was 2716 ± 1621 days (102–7483 days). New LREs (hepatocellular carcinoma (HCC) (n = 8), decompensation (n = 11), bleeding varices (n = 8)) developed in 18 patients. Twenty-four and twelve patients developed extrahepatic cancers and MACEs, respectively. The median FIB-4 index was 1.255; we divided our cohort into two groups according to this (FIB4 Low, FIB4 Hi). The incidence of HCC tended to be higher in FIB4 Hi (n = 7) than in FIB4 Low (n = 1). The incidence of LREs was significantly higher in FIB4 Hi (n = 17) than in FIB4 Low (n = 1). The incidence of extrahepatic cancers was significantly higher in FIB4 Hi (n = 20) than in FIB4 Low (n = 4); the incidence of MACEs was also significantly higher in FIB4 Hi (n = 10) than in FIB4 Low (n = 2). The FIB-4 index is a useful biomarker for predicting not only LREs but also extrahepatic cancers and MACEs. Full article
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