☆ 4.1 Review

Metabolic-associated fatty liver disease: From simple steatosis toward liver cirrhosis and potential complications. Proceedings of the Third Translational Hepatology Meeting, organized by the Spanish Association for the Study of the Liver (AEEH)

GASTROENTEROLOGIA Y HEPATOLOGIA (2022)

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Overlooked subclinical portal hypertension in non-cirrhotic NAFLD: Is it real and how to measure it?

Gyorgy Baffy et al.

Summary: There have been clinical and experimental advances in detecting, measuring, and understanding subclinical portal hypertension in non-alcoholic fatty liver disease (NAFLD). The current understanding of the disease may need to be revisited, and new methods of measurement and a better understanding of the impact of subclinical portal hypertension on disease outcomes are needed.

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Summary: Macrophages, key cellular components of the liver, play essential roles in maintaining liver homeostasis, injury and repair processes in liver diseases. Kupffer cells and monocyte-derived macrophages contribute significantly to tissue inflammation and injury, but exhibit different functional responses in distinct liver diseases.

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Agreement between wedged hepatic venous pressure and portal pressure in non-alcoholic steatohepatitis-related cirrhosis

Jose Ferrusquia-Acosta et al.

Summary: In patients with decompensated cirrhosis caused by non-alcoholic steatohepatitis, wedge hepatic vein pressure does not estimate portal pressure as accurately as in patients with alcohol-or HCV-related cirrhosis, mainly because of portal pressure underestimation.

JOURNAL OF HEPATOLOGY (2021)

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Review Pharmacology & Pharmacy

Extracellular vesicles in hepatology: Physiological role,involvement in pathogenesis, and therapeutic opportunities

Maria Azparren-Angulo et al.

Summary: The number of publications on Extracellular Vesicles (EVs) released by liver cells has exponentially increased since the first descriptions in 2008, indicating the growing interest in the importance of cell-to-cell communication and the potential of these vesicles in diagnostics and therapeutics. This systematic review summarizes the works from the past decade and discusses the best opportunities for utilizing EVs in liver disease therapeutics.

PHARMACOLOGY & THERAPEUTICS (2021)

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Review Gastroenterology & Hepatology

The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis

Vicente Arroyo et al.

Summary: Systemic inflammation may be a key feature of acute decompensation of cirrhosis, affecting organ system function through various mechanisms and working synergistically with traditional pathways to contribute to the development of AD. It can exacerbate splanchnic vasodilation by overactivating the endogenous vasoconstrictor systems, leading to hypoperfusion in certain vascular beds such as the renal circulation. Additionally, systemic inflammation may cause immune-mediated tissue damage and induce significant metabolic changes.

JOURNAL OF HEPATOLOGY (2021)

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Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention

Daniel Q. Huang et al.

Summary: The prevalence of NAFLD-related HCC is projected to continue rising globally, with NASH expected to increase and obesity as a major risk factor. Urgent measures are needed to address this growing problem.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma

Jason Behary et al.

Summary: The study demonstrates that patients with NAFLD-HCC have dysbiosis in the gut microbiota, leading to modulation of peripheral immune responses and the induction of a T cell immunosuppressive phenotype.

NATURE COMMUNICATIONS (2021)

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In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal

Pierre-Antoine Soret et al.

Summary: NAFLD, associated with obesity and metabolic syndrome, is a common liver disease but lacks approved pharmacological treatments for NASH. Ongoing preclinical research is improving our understanding of NAFLD pathophysiology and identifying new therapeutic targets through various models.

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The Power of Plasticity?Metabolic Regulation of Hepatic Stellate Cells

Parth Trivedi et al.

Summary: Hepatic stellate cells play a crucial role in regulating physiological and pathological responses in the liver, particularly in chronic liver injury. They drive hepatic fibrosis and are involved in inflammation and cancer by adapting metabolic pathways to meet increased energy demands.

CELL METABOLISM (2021)

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Heterogeneity of HSCs in a Mouse Model of NASH

Sara Brin Rosenthal et al.

Summary: This study utilized single-cell RNA sequencing to characterize the phenotypic changes of hepatic stellate cells (HSCs) in a NASH model, revealing unexpected heterogeneity of HSC phenotypes under normal and injured states. The NASH livers showed four distinct HSC clusters, including one representing the classic fibrogenic myofibroblast, while livers with NASH regression had one cluster of inactivated HSCs similar to quiescent HSCs.

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Role of liver sinusoidal endothelial cells in liver diseases

Jordi Gracia-Sancho et al.

Summary: Liver sinusoidal endothelial cells (LSECs) play crucial roles in hepatic homeostasis, being involved in regulation of vascular tone, inflammation, and thrombosis, as well as control of the hepatic immune response. Dysregulations of LSECs in the context of liver disease and hepatocellular carcinoma make them potential therapeutic targets.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease-Current Knowledge, Mechanisms and Perspectives

Kristoffer Kjaergaard et al.

Summary: NAFLD is associated with cognitive dysfunction, potentially independent of other factors, affecting the gut microbiota and urea cycle function, leading to systemic ammonia accumulation and further promoting systemic inflammation.

JOURNAL OF CLINICAL MEDICINE (2021)

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PKM2-dependent metabolic skewing of hepatic Th17 cells regulates pathogenesis of non-alcoholic fatty liver disease

Maria E. Moreno-Fernandez et al.

Summary: Recent evidence suggests that Th17 cells play a key role in the pathogenesis of NAFLD, with a distinct population of inflammatory hepatic CXCR3(+)Th17 cells exacerbating the disease. The pathogenic characteristics of these cells include increased chromatin accessibility, glycolytic output, and production of IL-17A, IFN-γ, and TNF-α. Modulation of glycolysis pathways can potentially reverse the inflammatory vigor of ihTh17 cells and severity of NAFLD.

CELL METABOLISM (2021)

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Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis

Roser Pinyol et al.

Summary: This study revealed higher rates of ACVR2A mutations (10%) in NASH-related hepatocellular carcinoma (HCC), along with a novel mutational signature that distinguishes NASH-HCC from HCCs of other etiologies.

JOURNAL OF HEPATOLOGY (2021)

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Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications

Qianqian Xu

Summary: Different types of hepatic cells used in 3D liver models, including primary human hepatocytes, human hepatic cancer cell lines, and stem cell-derived hepatocyte-like cells, exhibit diverse phenotypes and have distinct advantages in different research fields like hepatotoxicity study, personalized medicine, and regenerative medicine.

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NASH limits anti-tumour surveillance in immunotherapy-treated HCC

Dominik Pfister et al.

Summary: The study investigated the impact of NASH on immunotherapy response in HCC patients and found that NASH-HCC may be less responsive to immunotherapy. Aberrant T cell activation caused by NASH-related tissue damage led to impaired immune surveillance in HCC patients.

NATURE (2021)

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Metabolic-associated fatty liver disease and lipoprotein metabolism

Joerg Heeren et al.

Summary: MAFLD is characterized by pathological accumulation of triglycerides in hepatocytes and is closely related to disturbances in systemic energy metabolism. Liver plays a central role in lipid metabolism, with excessive hepatic triglyceride synthesis being a key factor in the development of MAFLD. Interventions targeting lipid storage and energy combustion in adipose tissues may help ameliorate MAFLD.

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Fat: Quality, or Quantity? What Matters Most for the Progression of Metabolic Associated Fatty Liver Disease (MAFLD)

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Summary: This study found that diets high in Palmitic Acid (PA), mainly sourced from palm oil, may lead to obesity, high cholesterol, more severe liver injury, and fibrosis, while diets high in trans-fat may result in glucose intolerance and elevated liver enzymes. Temporary withdrawal of these unhealthy diets can reverse symptoms of Metabolic Syndrome and Fatty Liver Disease, but mild hepatic inflammation remains detectable in the high PA diet groups.

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Could protein content of Urinary Extracellular Vesicles be useful to detect Cirrhosis in Alcoholic Liver Disease?

Esperanza Gonzalez et al.

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NASH-related increases in plasma bile acid levels depend on insulin resistance

Guillaume Grzych et al.

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JHEP REPORTS (2021)

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Article Gastroenterology & Hepatology

An Experimental DUAL Model of Advanced Liver Damage

Raquel Benede-Ubieto et al.

Summary: This study successfully developed a preclinical DUAL model in mice that showed symptoms of fatty liver diseases associated with both alcohol consumption and metabolic risk. The model exhibited obesity, glucose intolerance, liver damage, steatohepatitis, fibrosis, inflammation in white adipose tissue, and dysregulated molecular pathways similar to human steatohepatitis, making it a valuable tool for developing therapeutic targets.

HEPATOLOGY COMMUNICATIONS (2021)

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Molecular Profiling of Decompensated Cirrhosis by a Novel MicroRNA Signature

Ana Garcia Garcia de Paredes et al.

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HEPATOLOGY COMMUNICATIONS (2021)

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Human Nonalcoholic Steatohepatitis on a Chip

May S. Freag et al.

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HEPATOLOGY COMMUNICATIONS (2021)

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Sandro Nuciforo et al.

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Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis

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Article Gastroenterology & Hepatology

C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

Esther Zimmermann et al.

JOURNAL OF HEPATOLOGY (2011)

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Article Genetics & Heredity

Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

Stefano Romeo et al.

NATURE GENETICS (2008)

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