Pathophysiology Articles

? Gain an understanding of the pathogenesis and natural course of NAFLD and NASH.

MAFLD: brain-gut-liver axis and insulin resistance

Authors: Rebelos E, Iozzo P, Guzzardi MA, et al.
Published in World J Gastroenterol 2021
There are many complex physio-pathologic connections within the brain, gut, and liver axis. This review by E. Rebelos et al. (University of Turku, Finland) is focused on the early pathophysiology of brain, gut, and liver axis in the context of insulin resistance and specifically addresses two pillars of hepatic insulin resistance....
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Genetic and epigenetic factors determining NAFLD risk

Authors: Jonas W, Schurmann A.
Published in Mol Metab 2021
Predicting the individual risk of NAFLD and determining the probability of disease progression is the basis for further developing prevention and treatment strategies. This requires knowledge of the genetic and epigenetic modifiers of NAFLD for genotype-guided risk stratification...
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Increased plasma XOR activity induced by NAFLD/NASH and its possible involvement in vascular neointimal proliferation

Authors: Kawachi Y, Fujishima Y, Nishizawa H, et al.
Published in JCI Insight 2021
Xanthine oxidoreductase is an enzyme that catalyses hypoxanthine to xanthine and xanthine to uric acid, respectively. However, the underlying mechanisms of increased plasma xanthine oxidoreductase and its pathological roles in systemic diseases, such as atherosclerosis, are not fully understood...
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Sugar and fat increase the risk of advanced liver disease

Authors: Manka P, Syn WK.
Published in Dig Dis Sci 2021
In this editorial, P. Manka Essen University Hospital, Germany) and W. K. Syn (Medical University of South Carolina, USA) comment a study by Benhammou and colleagues, who evaluated the effects of NAFLD risk factors including obesity and diabetes on the long-term outcomes of patients with HCV treated with direct-acting antivirals...
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NAFLD and hepatic sexual dimorphism

Authors: Lefebvre P, Staels B.
Published in Nat Rev Endocrinol 2021
This review by Philippe Lefebvre and Bart Staels (INSERM, CHU Lille, Institut Pasteur de Lille, France) discusses the accumulating evidence of sexual dimorphism in NAFLD. Liver pathophysiology is sexually dimorphic, and male individuals predominantly show more severe stages of non-alcoholic fatty liver, NASH and fibrosis than do female individuals...
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Review: NAFLD, driver of chronic kidney disease

Authors: Byrne CD, Targher G.
Published in J Hepatol 2020
The relationship between NAFLD and chronic kidney disease has attracted much attention recently. NAFLD and chronic kidney disease may share common pathogenic mechanisms, such as insulin resistance, type 2 diabetes mellitus, hyperlipidemia and obesity, and thus may potentially share same therapeutic targets. Growing evidence suggests...
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Dynamic changes in liver macrophage subsets during NASH

Authors: Daemen S, Gainullina A, Kalugotla G, et al.
Published in Cell Rep 2021
Macrophage-mediated inflammation is critical in the pathogenesis of NASH. However, the underlying mechanisms remain unclear. In this study, S. Daemen et al. (Washington University School of Medicine, St. Louis, MI, USA) evaluated intra-hepatic macrophage composition in a mouse model of obesity with NAFLD and in a model of NASH...
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Accumulation of T cells in NASH-affected livers

Authors: Pfister D, Nunez NG, Pinyol R, et al.
Published in Nature 2021
Immunotherapy has been approved for treating hepatocellular carcinoma (HCC), but biomarker-based stratification of patients for optimal response to therapy is an unmet need. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded..
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The global burden of cirrhosis: the role of NAFLD

Authors: Jepsen P, Younossi ZM
Published in J Hepatol 2021
The World Health Organization’s metric of public health burden is the disability-adjusted life-year (DALY), the sum of years of life lost due to premature death and years of life lived with disability. Cirrhosis was responsible for 26.8% fewer DALYs in 2019 than in 1990, which is positive...
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Clinical indicators for progression of NASH to cirrhosis

Authors: Seen TK, Sayed M, Bilal M, et al.
Published in World J Gastroenterol 2021
Providing clinicians with the tools to diagnose and treat the full spectrum of NAFLD will help prevent known complications such as cirrhosis and HCC and improve quality of life for these patients.This article by T. K. Seen et al. (Icahn School of Medicine, Elmhurst Hospital and Mount Sinai Hospital, USA) discusses...
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Alterations in gut microbiota in NASH

Authors: Plaza-Diaz J, Solis-Urra P, Aragon-Vela J, et al.
Published in Biomedicines 2021
NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defence and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH...
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From NAFLD/NASH to HCC: role of mitochondrial defects

Authors: Longo M, Paolini E, Meroni M, et al.
Published in Int J Mol Sci 2021
This review by M. Longo et al. (IRCCS – Università degli Studi di Milano, Italy) discusses how mitochondrial defects may be translated into causative explanations of NAFLD-driven hepatocellular carcinoma. Acting as central metabolic hubs, the mitochondria rapidly adapt to different metabolic alterations...
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