Pathophysiology Articles

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

From NAFLD to NASH: determining disease progression and regression rates

Authors: Noureddin and Wong
Published in Clinical Gastroenterology and Hepatology (May 2023)
The spectrum of non-alcoholic fatty liver disease (NAFLD) is divisible into three stages: 1) NAFL, 2) non-alcoholic steatohepatitis (NASH), NAFLD’s progressive and inflammatory subtype, and 3) NAFLD or NASH with fibrosis, whose stages range from F0-4.
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Phospholipid depletion and NAFLD pathophysiology: findings from lipidomics

Authors: Mocciaro G, Allison M, Jenkins B et al.
Published in Molecular Metabolism (April 2023)
Along with its association with metabolic syndrome, NAFLD is closely linked with mixed dyslipidaemia (reduced high-density lipoprotein cholesterol (HDL-C) and increased very low-density lipoprotein triglycerides (VLDL-TG)).
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T2D-Related Complications and its Impact on Fibrosis Levels: an Emerging Association?

Authors: Trivedi HD, Tran Q, Fricker Z et al.
Published in Annals of hepatology 2023
Patients with T2D complications have a 4.5x greater risk of developing fibrosis, independent of HbA1c levels. FIB-4 index can help identify diabetic patients at highest risk, improving primary care screening.
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Non-Invasive Tests to Stratify NAFLD Based on Liver-Related Events: a Review

Authors: Boursier J, Hagström H, Ekstedt M, et al.
Published in J Hepatol 2022
FIB4 and VCTE show promise in predicting prognosis for NAFLD patients. These non-invasive tests offer an alternative to liver biopsies for risk stratification. Quick and easily prescribed, they can streamline referrals and specialized management. A sequential algorithm with FIB4 and VCTE may improve NAFLD care.
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Inflammation in non-alcoholic fatty liver disease: Part 1

Authors: Wiering L & Tacke F
Published in J Endocrinol 2022
Non-alcoholic fatty liver disease (NAFLD) has a more progressive form, non-alcoholic steatohepatitis (NASH). In both conditions, inflammation is a key driver of the pathogenesis. There are various causes of metabolic injury in the conditions, leading to the activation of different immune cells such as hepatic Kupffer cells.
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Inflammation in non-alcoholic fatty liver disease: Part 2

Authors: Wiering L & Tacke F
Published in J Endocrinol 2022
Non-alcoholic fatty liver disease (NAFLD) has a more progressive form, non-alcoholic steatohepatitis (NASH). In both conditions, inflammation is a key driver of the pathogenesis. Current treatments mostly focus on promoting weight loss (through encouraging lifestyle changes, or, if necessary, bariatric surgery) and improving comorbidities through pharmacotherapy, such as type 2 diabetes.
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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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