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  1. Article ; Online: Metabolic dysfunction-associated steatotic liver disease: Evolution of the final terminology.

    Portincasa, Piero / Baffy, Gyorgy

    European journal of internal medicine

    2024  

    Abstract: The medical term nonalcoholic fatty liver disease (NAFLD) was coined in 1986 for a condition that has since become the most prevalent liver disorder worldwide. In the last 3 years, the global professional community launched 2 consecutive efforts to purge ...

    Abstract The medical term nonalcoholic fatty liver disease (NAFLD) was coined in 1986 for a condition that has since become the most prevalent liver disorder worldwide. In the last 3 years, the global professional community launched 2 consecutive efforts to purge NAFLD from the medical dictionary and recommended new terms based on disease pathophysiology rather than distinction from similar conditions featuring liver steatosis. A consensus by renowned clinical scholars primarily residing in the Asian-Pacific region introduced metabolic dysfunction-associated fatty liver disease (MAFLD) as a new name to replace NAFLD in 2020. In 2023, a nomenclature and classification resulting in the term metabolic dysfunction-associated steatotic liver disease (MASLD) was developed by a large expert panel under the auspices of leading liver societies from Europe and Americas. These marked and rapid shifts in nomenclature have garnered the attention of many researchers and clinicians across the globe due to the multilevel impact of a frequent and potentially progressive chronic liver disease in both adult and pediatric populations. The proposed terminologies differ in several ways but they have more in common than differences. They both capture key features of liver disease associated with cardiometabolic risk factors and with significant impact on all-cause and liver-related mortality. The framework of MASLD has incorporated many innovative aspects of MAFLD and while several conceptual disparities remain a work in progress, global efforts should focus on new insights into disease pathogenesis, outcome trajectories, prevention, and treatment. Here, some of these challenges are discussed to facilitate this process.
    Language English
    Publishing date 2024-04-22
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1038679-8
    ISSN 1879-0828 ; 0953-6205
    ISSN (online) 1879-0828
    ISSN 0953-6205
    DOI 10.1016/j.ejim.2024.04.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Is the name 'NAFLD' too big to fail? Let's keep it for 'nutrition-associated fatty liver disease'.

    Baffy, Gyorgy

    Journal of hepatology

    2020  Volume 74, Issue 4, Page(s) 988

    MeSH term(s) Humans ; Non-alcoholic Fatty Liver Disease/epidemiology ; Non-alcoholic Fatty Liver Disease/etiology ; Nutritional Status
    Language English
    Publishing date 2020-12-16
    Publishing country Netherlands
    Document type Letter ; Comment
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2020.11.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Gut Microbiota and Cancer of the Host: Colliding Interests.

    Baffy, Gyorgy

    Advances in experimental medicine and biology

    2020  Volume 1219, Page(s) 93–107

    Abstract: Cancer develops in multicellular organisms from cells that ignore the rules of cooperation and escape the mechanisms of anti-cancer surveillance. Tumorigenesis is jointly encountered by the host and microbiota, a vast collection of microorganisms that ... ...

    Abstract Cancer develops in multicellular organisms from cells that ignore the rules of cooperation and escape the mechanisms of anti-cancer surveillance. Tumorigenesis is jointly encountered by the host and microbiota, a vast collection of microorganisms that live on the external and internal epithelial surfaces of the body. The largest community of human microbiota resides in the gastrointestinal tract where commensal, symbiotic and pathogenic microorganisms interact with the intestinal barrier and gut mucosal lymphoid tissue, creating a tumor microenvironment in which cancer cells thrive or perish. Aberrant composition and function of the gut microbiota (dysbiosis) has been associated with tumorigenesis by inducing inflammation, promoting cell growth and proliferation, weakening immunosurveillance, and altering food and drug metabolism or other biochemical functions of the host. However, recent research has also identified several mechanisms through which gut microbiota support the host in the fight against cancer. These mechanisms include the use of antigenic mimicry, biotransformation of chemotherapeutic agents, and other mechanisms to boost anti-cancer immune responses and improve the efficacy of cancer immunotherapy. Further research in this rapidly advancing field is expected to identify additional microbial metabolites with tumor suppressing properties, map the complex interactions of host-microbe 'transkingdom network' with cancer cells, and elucidate cellular and molecular pathways underlying the impact of specific intestinal microbial configurations on immune checkpoint inhibitor therapy.
    MeSH term(s) Dysbiosis ; Gastrointestinal Microbiome/immunology ; Gastrointestinal Microbiome/physiology ; Humans ; Intestines/immunology ; Intestines/microbiology ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/therapy ; Tumor Microenvironment
    Language English
    Publishing date 2020-02-28
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 410187-X
    ISSN 0065-2598
    ISSN 0065-2598
    DOI 10.1007/978-3-030-34025-4_5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Sarcopenic obesity in liver cancer: it is SO complicated.

    Baffy, Gyorgy

    Hepatobiliary surgery and nutrition

    2019  Volume 8, Issue 5, Page(s) 560–562

    Language English
    Publishing date 2019-09-30
    Publishing country China (Republic : 1949- )
    Document type Editorial ; Comment
    ZDB-ID 2812398-0
    ISSN 2304-389X ; 2304-3881
    ISSN (online) 2304-389X
    ISSN 2304-3881
    DOI 10.21037/hbsn.2019.07.16
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Digital Rectal Examination: Is It Warranted in the Endoscopy Suite?

    Baffy, Gyorgy

    The American journal of gastroenterology

    2018  Volume 114, Issue 2, Page(s) 355

    MeSH term(s) Diagnostic Tests, Routine ; Digital Rectal Examination ; Endoscopy ; Rectum
    Language English
    Publishing date 2018-10-25
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 390122-1
    ISSN 1572-0241 ; 0002-9270
    ISSN (online) 1572-0241
    ISSN 0002-9270
    DOI 10.1038/s41395-018-0392-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease.

    Baffy, Gyorgy

    Digestive diseases and sciences

    2018  Volume 63, Issue 3, Page(s) 563–576

    Abstract: Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical ... ...

    Abstract Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often complicated by clinically significant portal hypertension, which is primarily caused by increased intrahepatic vascular resistance. Liver fibrosis has been identified as a critical determinant of this process. However, there is evidence that portal venous pressure may begin to rise in the earliest stages of NAFLD when fibrosis is far less advanced or absent. The biological and clinical significance of these early changes in sinusoidal homeostasis remains unclear. Experimental and human observations indicate that sinusoidal space restriction due to hepatocellular lipid accumulation and ballooning may impair sinusoidal flow and generate shear stress, increasingly disrupting sinusoidal microcirculation. Sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells are key partners of hepatocytes affected by NAFLD in promoting endothelial dysfunction through enhanced contractility, capillarization, adhesion and entrapment of blood cells, extracellular matrix deposition, and neovascularization. These biomechanical and rheological changes are aggravated by a dysfunctional gut-liver axis and splanchnic vasoregulation, culminating in fibrosis and clinically significant portal hypertension. We may speculate that increased portal venous pressure is an essential element of the pathogenesis across the entire spectrum of NAFLD. Improved methods of noninvasive portal venous pressure monitoring will hopefully give new insights into the pathobiology of NAFLD and help efforts to identify patients at increased risk for adverse outcomes. In addition, novel drug candidates targeting reversible components of aberrant sinusoidal circulation may prevent progression in NAFLD.
    MeSH term(s) Humans ; Hypertension, Portal/etiology ; Hypertension, Portal/pathology ; Hypertension, Portal/therapy ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/pathology ; Non-alcoholic Fatty Liver Disease/physiopathology
    Language English
    Publishing date 2018-03
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 304250-9
    ISSN 1573-2568 ; 0163-2116
    ISSN (online) 1573-2568
    ISSN 0163-2116
    DOI 10.1007/s10620-017-4903-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Potential mechanisms linking gut microbiota and portal hypertension.

    Baffy, Gyorgy

    Liver international : official journal of the International Association for the Study of the Liver

    2018  Volume 39, Issue 4, Page(s) 598–609

    Abstract: Gut microbiota is the largest collection of commensal micro-organisms in the human body, engaged in reciprocal cellular and molecular interactions with the liver. This mutually beneficial relationship may break down and result in dysbiosis, associated ... ...

    Abstract Gut microbiota is the largest collection of commensal micro-organisms in the human body, engaged in reciprocal cellular and molecular interactions with the liver. This mutually beneficial relationship may break down and result in dysbiosis, associated with disease phenotypes. Altered composition and function of gut microbiota has been implicated in the pathobiology of nonalcoholic fatty liver disease (NAFLD), a prevalent condition linked to obesity, insulin resistance and endothelial dysfunction. NAFLD may progress to cirrhosis and portal hypertension, which is the result of increased intrahepatic vascular resistance and altered splanchnic circulation. Gut microbiota may contribute to rising portal pressure from the earliest stages of NAFLD, although the significance of these changes remains unclear. NAFLD has been linked to lower microbial diversity and weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defence and inflammation. Moreover, disrupted host-microbial metabolic interplay alters bile acid signalling and the release of vasoregulatory gasotransmitters. These perturbations become prominent in cirrhosis, increasing the risk of clinically significant portal hypertension and leading to bacterial translocation, sepsis and acute-on-chronic liver failure. Better understanding of the gut-liver axis and identification of novel microbial molecular targets may yield specific strategies in the prevention and management of portal hypertension.
    MeSH term(s) Animals ; Bacterial Translocation ; Disease Models, Animal ; Disease Progression ; Dysbiosis/immunology ; Dysbiosis/microbiology ; Gastrointestinal Microbiome ; Humans ; Hypertension, Portal/etiology ; Hypertension, Portal/pathology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/microbiology ; Liver/physiopathology ; Liver Cirrhosis/complications ; Liver Cirrhosis/microbiology ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/pathology
    Language English
    Publishing date 2018-11-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2102783-3
    ISSN 1478-3231 ; 1478-3223
    ISSN (online) 1478-3231
    ISSN 1478-3223
    DOI 10.1111/liv.13986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Mitochondrial uncoupling in cancer cells: Liabilities and opportunities.

    Baffy, Gyorgy

    Biochimica et biophysica acta. Bioenergetics

    2017  Volume 1858, Issue 8, Page(s) 655–664

    Abstract: Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. ... ...

    Abstract Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life. Uncoupling proteins (UCPs), a group of the solute carrier family of transporters, may remove some of the physiologic constraints that link mitochondrial respiration and ATP synthesis by mediating inducible proton leak and limiting oxidative cell injury. This important property makes UCPs an ancient partner in the metabolic adaptation of cancer cells. Efforts are underway to explore the therapeutic opportunities stemming from the intriguing relationship of UCPs and cancer. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacokinetics ; Cell Hypoxia ; Cell Line, Tumor ; Cellular Reprogramming ; Drug Resistance, Neoplasm/physiology ; Drug Synergism ; Energy Metabolism ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Mitochondrial Uncoupling Proteins/physiology ; Models, Biological ; Neoplasm Proteins/physiology ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Oxidative Phosphorylation/drug effects ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Symbiosis ; Uncoupling Agents/pharmacology ; Uncoupling Agents/therapeutic use
    Chemical Substances Antineoplastic Agents ; Mitochondrial Uncoupling Proteins ; Neoplasm Proteins ; Reactive Oxygen Species ; Uncoupling Agents
    Language English
    Publishing date 2017-01-11
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0005-2728 ; 0006-3002 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0005-2728 ; 0006-3002 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbabio.2017.01.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Overlooked subclinical portal hypertension in non-cirrhotic NAFLD: Is it real and how to measure it?

    Baffy, Gyorgy / Bosch, Jaume

    Journal of hepatology

    2021  Volume 76, Issue 2, Page(s) 458–463

    Abstract: Clinical and experimental advances related to the detection, magnitude and pathobiology of subclinical portal hypertension in non-alcoholic fatty liver disease (NAFLD), primarily observed in the presence of non-alcoholic steatohepatitis (NASH), prompt us ...

    Abstract Clinical and experimental advances related to the detection, magnitude and pathobiology of subclinical portal hypertension in non-alcoholic fatty liver disease (NAFLD), primarily observed in the presence of non-alcoholic steatohepatitis (NASH), prompt us to revisit current disease paradigms. Hepatic venous pressure gradient (HVPG) has been reported to underestimate portal pressure in NASH-related cirrhosis, while inaccuracy is more likely in non-cirrhotic livers, indicating a potential need for new and preferably non-invasive methods of measurement. Although clinically significant portal hypertension (HVPG ≥10 mmHg) retains its prognostic significance in NASH, subclinical portal hypertension (HVPG 6.0-9.5 mmHg) has been repeatedly detected in patients with NAFLD in the absence of cirrhosis or even significant fibrosis whereas the impact of these findings on disease outcomes remains unclear. Mechanocrine signalling pathways in various types of liver cell reveal a molecular basis for the adverse effects of subclinical portal hypertension and suggest a bidirectional relationship between portal pressure and fibrosis. These findings may guide efforts to improve risk assessment and identify novel therapeutic targets in NAFLD.
    MeSH term(s) Humans ; Hypertension, Portal/diagnosis ; Hypertension, Portal/physiopathology ; Non-alcoholic Fatty Liver Disease/complications ; Non-alcoholic Fatty Liver Disease/physiopathology ; Prognosis ; Severity of Illness Index ; Weights and Measures/instrumentation ; Weights and Measures/standards
    Language English
    Publishing date 2021-10-02
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2021.09.029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Hepatocellular Carcinoma in Obesity: Finding a Needle in the Haystack?

    Baffy, György

    Advances in experimental medicine and biology

    2018  Volume 1061, Page(s) 63–77

    Abstract: Obesity has been implicated in the development of hepatocellular carcinoma (HCC), one of the most common malignancies worldwide with an increasing incidence in the United States. Obesity and associated metabolic disorders such as type II diabetes and the ...

    Abstract Obesity has been implicated in the development of hepatocellular carcinoma (HCC), one of the most common malignancies worldwide with an increasing incidence in the United States. Obesity and associated metabolic disorders such as type II diabetes and the metabolic syndrome are key factors in the development of nonalcoholic fatty liver disease (NAFLD) and promote several molecular mechanisms that may contribute to hepatocarcinogenesis. The vast majority of HCC occur in cirrhotic livers, but a subgroup of patients may develop HCC in non-advanced NAFLD. While the incidence rate for noncirrhotic HCC is low, the population-attributable fraction is still significant due to the extraordinary prevalence of obesity-associated liver disease. This is a challenge since HCC surveillance cannot be provided to the large population of non-advanced NAFLD in a cost-efficient way and requires enhanced risk stratification strategies. Recent advances may offer new clinical, laboratory, and genetic biomarkers and help us meet this important public health need.
    MeSH term(s) Carcinoma, Hepatocellular/epidemiology ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Diabetes Complications/epidemiology ; Diabetes Complications/metabolism ; Diabetes Complications/pathology ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Humans ; Liver Neoplasms/epidemiology ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Obesity/epidemiology ; Obesity/metabolism ; Obesity/pathology ; Risk Factors
    Language English
    Publishing date 2018-06-25
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-10-8684-7_6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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