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(Expert Views) Nonalcoholic Fatty Liver Disease: Pathogenesis, Clinical Diagnosis, and...
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(Expert Views) Nonalcoholic Fatty Liver Disease: Pathogenesis, Clinical Diagnosis, and Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 6399

Special Issue Editor

Dr. Hirsh D. Trivedi

E-Mail Website
Guest Editor
Karsh Division of Gastroenterology & Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Interests: IM gastroenterology; hepatology; nonalcoholic fatty liver disease

Special Issue Information

Dear Colleagues,

It is my pleasure to invite you to submit a manuscript to the Special Issue in Journal of Clinical Medicine entitled: (Expert Views) Nonalcoholic Fatty Liver Disease: Pathogenesis, Clinical Diagnosis, and Treatment. As you know, the incidence and prevalence of nonalcoholic fatty liver disease (NAFLD) is on the rise and an increasing amount of research is being conducted. NAFLD is afflicting the global population and is projected to become the leading cause of liver transplantation in the next decade. This poses a significant burden to our patients, the economy, and to healthcare system as a whole.

As the Guest Editor to this Special Issue, I look forward to accepting and publishing articles that highlight novel concepts for the diagnosis and management of NAFLD in attempts to increase awareness and optimize management protocols. We thank you for your contribution.

Dr. Hirsh D. Trivedi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nonalcoholic fatty liver disease
  • hepatic steatosis
  • liver fibrosis
  • metabolic syndrome
  • type 2 diabetes mellitus
  • liver biopsy
  • liver cancer
  • cardiovascular disease

Published Papers (5 papers)

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Editorial

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4 pages, 635 KiB  
Editorial
Post-Transplant Hepatic Steatosis: A Condition Not to Overlook
by Iyiad Alabdul Razzak, Michael P. Curry, Michelle Lai and Hirsh D. Trivedi
J. Clin. Med. 2023, 12(23), 7340; https://doi.org/10.3390/jcm12237340 - 27 Nov 2023
Viewed by 670
Abstract
Recurrent or de novo steatotic liver disease (SLD) following liver transplantation (LT) is a rising concern among liver transplant recipients [...] Full article
(This article belongs to the Special Issue (Expert Views) Nonalcoholic Fatty Liver Disease: Pathogenesis, Clinical Diagnosis, and Treatment)
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Research

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14 pages, 1342 KiB  
Article
Development and Internal Validation of a Model for Predicting Overall Survival in Subjects with MAFLD: A Cohort Study
by Caterina Bonfiglio, Angelo Campanella, Rossella Donghia, Antonella Bianco, Isabella Franco, Ritanna Curci, Claudia Beatrice Bagnato, Rossella Tatoli, Gianluigi Giannelli and Francesco Cuccaro
J. Clin. Med. 2024, 13(4), 1181; https://doi.org/10.3390/jcm13041181 - 19 Feb 2024
Viewed by 631
Abstract
Background & Aims: Fatty liver disease with metabolic dysfunction (MAFLD) is a new concept proposed to replace the previous concept of Non-Alcoholic Hepatic Steatosis (NAFLD). We developed and internally validated a prognostic model to predict the likelihood of death in a cohort [...] Read more.
Background & Aims: Fatty liver disease with metabolic dysfunction (MAFLD) is a new concept proposed to replace the previous concept of Non-Alcoholic Hepatic Steatosis (NAFLD). We developed and internally validated a prognostic model to predict the likelihood of death in a cohort of subjects with MAFLD. Methods: Our work involved two steps: the first was the construction of a bootstrapped multivariable Cox model for mortality risk prognosis and the second was its validation. Results: The study cohort included 1506 subjects, of which 907 were used for internal validation. Discriminant measures for the final model were R2D 0.6845 and Harrell’s C 0.8422 in the development and R2D 0.6930 and Harrell’s C 0.8465 in the validation. We used the nine independent prognostic factors selected by the LASSO Cox procedure and fitted by the bootstrap Cox survival model, and observed β were: Gender 0.356 1.42 (p < 0.008), Age 0.146 (p < 0.001), Glycemia 0.004 (p < 0.002), Total Cholesterol −0.0040 (p < 0.009), Gamma Glutamyl Transpeptidase 0.009 (p < 0.001), SBP 0.009 (p < 0.036), DBP −0.016 (p < 0.041), ALP 0.008 (p < 0.071) and Widowhood 0.550 (p < 0.001). Conclusions: We produced and validated a model to estimate the probability of death in subjects with MAFLD. The instruments we used showed satisfactory predictive capabilities. Full article
(This article belongs to the Special Issue (Expert Views) Nonalcoholic Fatty Liver Disease: Pathogenesis, Clinical Diagnosis, and Treatment)
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13 pages, 652 KiB  
Article
Steatotic Liver Disease and Sepsis Outcomes—A Prospective Cohort Study (SepsisFAT)
by Juraj Krznaric, Neven Papic, Nina Vrsaljko, Branimir Gjurasin, Marko Kutlesa and Adriana Vince
J. Clin. Med. 2024, 13(3), 798; https://doi.org/10.3390/jcm13030798 - 30 Jan 2024
Viewed by 688
Abstract
Background: While it has been shown that steatotic liver disease (SLD) is associated with systemic changes in immune response, the impact of SLD on sepsis outcomes has not yet been established. The aim of this study was to investigate the association between [...] Read more.
Background: While it has been shown that steatotic liver disease (SLD) is associated with systemic changes in immune response, the impact of SLD on sepsis outcomes has not yet been established. The aim of this study was to investigate the association between SLD and sepsis severity and outcomes. Methods: A prospective observational study included consecutively hospitalized adult patients with community-acquired sepsis during a 16-month period. Results: Of the 378 included patients (49.5% male, median age of 69, IQR 57–78 years), 174 (46%) were diagnosed with SLD. Patients with SLD were older and more frequently fulfilled the criteria for metabolic syndrome. There were no differences in the source and etiology of sepsis between the groups. Patients with SLD exhibited a higher incidence of acute kidney injury (29.3% vs. 17.6%), the need for renal replacement therapy (16.1% vs. 8.8%), and more frequent use of invasive mechanical ventilation (29.3% vs. 18.1%). In-hospital mortality was significantly higher in the SLD group (18.39% vs. 9.8%). The multivariable analysis indicated that SLD was associated with mortality (HR 2.82, 95% CI 1.40–5.71) irrespective of the other elements within metabolic syndrome. Conclusions: SLD might be associated with higher sepsis in-hospital mortality, and more frequent development of acute kidney and respiratory insufficiency requiring more critical care support. Full article
(This article belongs to the Special Issue (Expert Views) Nonalcoholic Fatty Liver Disease: Pathogenesis, Clinical Diagnosis, and Treatment)
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Review

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18 pages, 753 KiB  
Review
The Interplay between Liver Sinusoidal Endothelial Cells, Platelets, and Neutrophil Extracellular Traps in the Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease
by Iulia Minciuna, Madalina Gabriela Taru, Bogdan Procopet and Horia Stefanescu
J. Clin. Med. 2024, 13(5), 1406; https://doi.org/10.3390/jcm13051406 - 29 Feb 2024
Viewed by 940
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a societal burden due to the lack of effective treatment and incomplete pathophysiology understanding. This review explores the intricate connections among liver sinusoidal endothelial cells (LSECs), platelets, neutrophil extracellular traps (NETs), and coagulation disruptions in MASLD [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a societal burden due to the lack of effective treatment and incomplete pathophysiology understanding. This review explores the intricate connections among liver sinusoidal endothelial cells (LSECs), platelets, neutrophil extracellular traps (NETs), and coagulation disruptions in MASLD pathogenesis. In MASLD’s early stages, LSECs undergo capillarization and dysfunction due to excessive dietary macronutrients and gut-derived products. Capillarization leads to ischemic changes in hepatocytes, triggering pro-inflammatory responses in Kupffer cells (KCs) and activating hepatic stellate cells (HSCs). Capillarized LSECs show a pro-inflammatory phenotype through adhesion molecule overexpression, autophagy loss, and increased cytokines production. Platelet interaction favors leucocyte recruitment, NETs formation, and liver inflammatory foci. Liver fibrosis is facilitated by reduced nitric oxide, HSC activation, profibrogenic mediators, and increased angiogenesis. Moreover, platelet attachment, activation, α-granule cargo release, and NETs formation contribute to MASLD progression. Platelets foster fibrosis and microthrombosis, leading to parenchymal extinction and fibrotic healing. Additionally, platelets promote tumor growth, epithelial–mesenchymal transition, and tumor cell metastasis. MASLD’s prothrombotic features are exacerbated by insulin resistance, diabetes, and obesity, manifesting as increased von Willebrand factor, platelet hyperaggregability, hypo-fibrinolysis, and a prothrombotic fibrin clot structure. Improving LSEC health and using antiplatelet treatment appear promising for preventing MASLD development and progression. Full article
(This article belongs to the Special Issue (Expert Views) Nonalcoholic Fatty Liver Disease: Pathogenesis, Clinical Diagnosis, and Treatment)
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16 pages, 903 KiB  
Review
Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Screening, Diagnosis, and Treatment
by Stefano Ciardullo, Michela Vergani and Gianluca Perseghin
J. Clin. Med. 2023, 12(17), 5597; https://doi.org/10.3390/jcm12175597 - 27 Aug 2023
Cited by 7 | Viewed by 2862
Abstract
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~70% of patients with type 2 diabetes (T2D), with ~20% showing signs of advanced liver fibrosis. Patients with T2D are at an increased risk of developing cirrhosis, liver failure, [...] Read more.
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~70% of patients with type 2 diabetes (T2D), with ~20% showing signs of advanced liver fibrosis. Patients with T2D are at an increased risk of developing cirrhosis, liver failure, and hepatocellular carcinoma and their liver-related mortality is doubled compared with non-diabetic individuals. Nonetheless, the condition is frequently overlooked and disease awareness is limited both among patients and among physicians. Given recent epidemiological evidence, clinical practice guidelines recommend screening for NAFLD/MASLD and advanced liver fibrosis in patients with T2D. While many drugs are currently being tested for the treatment of NAFLD/MASLD, none of them have yet received formal approval from regulatory agencies. However, several classes of antidiabetic drugs (namely pioglitazone, sodium-glucose transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and multi-agonists) have shown favorable effects in terms of liver enzymes, liver fat content and, in some occasions, on histologic features such as inflammation and fibrosis. Therefore, diabetologists have the opportunity to actively treat NAFLD/MASLD, with a concrete possibility of changing the natural history of the disease. In the present narrative review, we summarize evidence and clinical recommendations for NAFLD/MAFLD screening in the setting of T2D, as well as on the effect of currently available glucose-lowering drugs on hepatic endpoints. Full article
(This article belongs to the Special Issue (Expert Views) Nonalcoholic Fatty Liver Disease: Pathogenesis, Clinical Diagnosis, and Treatment)
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