The outbreak of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has been recently declared a pandemic by the World Health ...Organization. In addition to its acute respiratory manifestations, SARS‐CoV‐2 may also adversely affect other organ systems. To date, however, there is a very limited understanding of the extent and management of COVID‐19‐related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extrapulmonary manifestations of COVID‐19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes the current understanding of the extrapulmonary complications caused by COVID‐19 to improve the management and prognosis of patients with COVID‐19.
Highlights
SARS‐CoV‐2 appears to adversely affect not only the respiratory system but also several other organ systems, including the urinary, cardiovascular, GI, and neurological systems.
To date, however, there is very limited understanding of the extent and management of COVID‐19‐related conditions outside of the pulmonary system.
Further research is needed to better understand the underlying mechanisms linking SARS‐CoV‐2 with the occurrence of multiple extra‐pulmonary complications.
Background ands Aims
NAFLD is associated with elevation of many cytokines, particularly IL‐6; however, the role of IL‐6 in NAFLD remains obscure. The aim of this study was to examine how ...myeloid‐specific IL‐6 signaling affects NAFLD by the regulation of antifibrotic microRNA‐223 (miR‐223) in myeloid cells.
Approach and Results
Patients with NAFLD or NASH and healthy controls were recruited, and serum IL‐6 and soluble IL‐6 receptor α (sIL‐6Rα) were measured. Compared to controls, serum IL‐6 and sIL‐6Rα levels were elevated in NAFLD/NASH patients. IL‐6 levels correlated positively with the number of circulating leukocytes and monocytes. The role of IL‐6 in NAFLD was investigated in Il6 knockout (KO) and Il6 receptor A (Il6ra) conditional KO mice after high‐fat diet (HFD) feeding. HFD‐fed Il6 KO mice had worse liver injury and fibrosis, but less inflammation, compared to wild‐type mice. Hepatocyte‐specific Il6ra KO mice had more steatosis and liver injury, whereas myeloid‐specific Il6ra KO mice had a lower number of hepatic infiltrating macrophages (IMs) and neutrophils with increased cell death of these cells, but greater liver fibrosis (LF), than WT mice. Mechanistically, the increased LF in HFD‐fed, myeloid‐specific Il6ra KO mice was attributable to the reduction of antifibrotic miR‐223 and subsequent up‐regulation of the miR‐223 target gene, transcriptional activator with PDZ‐binding motif (TAZ), a well‐known factor to promote NASH fibrosis. In vitro, IL‐6 treatment up‐regulated exosome biogenesis‐related genes and subsequently promoted macrophages to release miR‐223‐enriched exosomes that were able to reduce profibrotic TAZ expression in hepatocytes by exosomal transfer. Finally, serum IL‐6 and miR‐223 levels were elevated and correlated with each other in NAFLD patients.
Conclusions
Myeloid‐specific IL‐6 signaling inhibits LF through exosomal transfer of antifibrotic miR‐223 into hepatocytes, providing therapeutic targets for NAFLD therapy.
Non‐alcoholic fatty liver disease (NAFLD), recently re‐defined and re‐classified as metabolic dysfunction‐associated fatty liver disease (MAFLD), has become increasingly prevalent and emerged as a ...public health problem worldwide. To date, the precise pathogenic mechanisms underpinning MAFLD are not entirely understood, and there is no effective pharmacological therapy for NAFLD/MAFLD. As a newly discovered form of iron‐dependent programmed cell death, ferroptosis can be involved in the development and progression of various chronic diseases, but the pathogenic connections and mechanisms that link MAFLD and ferroptosis have not been fully elucidated. The main characteristics of ferroptosis are the accumulation of lipid peroxides and reactive oxygen species. In this brief narrative review, the mechanisms of ferroptosis and its putative pathogenic role in MAFLD are discussed to highlight potential new research directions and ideas for the prevention and treatment of MAFLD.
LINKED CONTENT
This article is linked to Magherman et al papers. To view these articles, visit
https://doi.org/10.1111/apt.17388
and
https://doi.org/10.1111/apt.17738
MAFLD: How is it different from NAFLD? Gofton, Cameron; Upendran, Yadhavan; Zheng, Ming-Hua ...
Clinical and molecular hepatology,
02/2023, Letnik:
29, Številka:
Suppl
Journal Article
Recenzirano
Odprti dostop
"Metabolic dysfunction-associated fatty liver disease (MAFLD)" is the term suggested in 2020 to refer to fatty liver disease related to systemic metabolic dysregulation. The name change from ...nonalcoholic fatty liver disease (NAFLD) to MAFLD comes with a simple set of criteria to enable easy diagnosis at the bedside for the general medical community, including primary care physicians. Since the introduction of the term, there have been key areas in which the superiority of MAFLD over the traditional NAFLD terminology has been demonstrated, including for the risk of liver and extrahepatic mortality, disease associations, and for identifying high-risk individuals. Additionally, MAFLD has been adopted by a number of leading pan-national and national societies due to its concise diagnostic criterion, removal of the requirement to exclude concomitant liver diseases, and reduction in the stigma associated with this condition. The current article explores the differences between MAFLD and NAFLD diagnosis, areas of benefit, some potential limitations, and how the MAFLD terminology has opened up new fields of research.
Liver injury is common in patients with COVID‐19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID‐19 in a patient who ...underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID‐19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.
This report presents the clinic features, treatment, and fatal outcome in a liver transplant recipient with COVID‐19.
Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the ...clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.
Background and Aims
Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study ...investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin‐binding sites (FGF1△HBS) against NAFLD.
Approach and Results
FGF1△HBS administration was effective in 9‐month‐old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1△HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45‐related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1△HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate–activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD‐like oxidative damage and lipid accumulation could be reversed by FGF1△HBS. In palmitate‐treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1△HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1△HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver‐specific AMPK knockout abolished therapeutic effects of FGF1△HBS against high‐fat/high‐sucrose diet–induced hepatic steatosis. Moreover, FGF1△HBS improved high‐fat/high‐cholesterol diet–induced steatohepatitis and fibrosis in apolipoprotein E knockout mice.
Conclusions
These findings indicate that FGF1△HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.
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