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Nasr P, Jönsson C, Ekstedt M, Kechagias S. Non-metabolic causes of steatotic liver disease. METABOLISM AND TARGET ORGAN DAMAGE 2023; 3. [DOI: 10.20517/mtod.2023.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Hepatic steatosis is caused by exaggerated hepatic lipid accumulation and is a common histological and radiological finding. Non-alcoholic fatty liver disease (NAFLD), or metabolic dysfunction associated steatotic liver disease (MASLD), is highly associated with metabolic syndrome and represents the most common cause of hepatic steatosis. However, since several comorbidities, lifestyle factors, and drugs can cause hepatic steatosis, MASLD is, to some extent, a diagnosis of exclusion. Nevertheless, initiatives have been taken to encompass positive (instead of negative) criteria for diagnosis - such as the presence of cardiometabolic risk factors together with hepatic steatosis. Nonetheless, before confirming a patient with MASLD, it is essential to map and evaluate other causes of fatty liver disease or steatotic liver disease. Several causes of hepatic steatosis have been identified in studies; however, the study cohorts are scarce and often anecdotal. Additionally, many studies have shown correlation without proving causation, and many are retrospective without reporting relevant patient characteristics and comorbidities - making it difficult to draw conclusions regarding the underlying etiology or present comorbidity of hepatic steatosis. In this narrative review, we aimed to identify and summarize present studies evaluating the impact of the most common and often suggested causes of hepatic steatosis.
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Waddell T, Namburete AIL, Duckworth P, Eichert N, Thomaides-Brears H, Cuthbertson DJ, Despres JP, Brady M. Bayesian networks and imaging-derived phenotypes highlight the role of fat deposition in COVID-19 hospitalisation risk. FRONTIERS IN BIOINFORMATICS 2023; 3:1163430. [PMID: 37293292 PMCID: PMC10244647 DOI: 10.3389/fbinf.2023.1163430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 05/08/2023] [Indexed: 06/10/2023] Open
Abstract
Objective: Obesity is a significant risk factor for adverse outcomes following coronavirus infection (COVID-19). However, BMI fails to capture differences in the body fat distribution, the critical driver of metabolic health. Conventional statistical methodologies lack functionality to investigate the causality between fat distribution and disease outcomes. Methods: We applied Bayesian network (BN) modelling to explore the mechanistic link between body fat deposition and hospitalisation risk in 459 participants with COVID-19 (395 non-hospitalised and 64 hospitalised). MRI-derived measures of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat were included. Conditional probability queries were performed to estimate the probability of hospitalisation after fixing the value of specific network variables. Results: The probability of hospitalisation was 18% higher in people living with obesity than those with normal weight, with elevated VAT being the primary determinant of obesity-related risk. Across all BMI categories, elevated VAT and liver fat (>10%) were associated with a 39% mean increase in the probability of hospitalisation. Among those with normal weight, reducing liver fat content from >10% to <5% reduced hospitalisation risk by 29%. Conclusion: Body fat distribution is a critical determinant of COVID-19 hospitalisation risk. BN modelling and probabilistic inferences assist our understanding of the mechanistic associations between imaging-derived phenotypes and COVID-19 hospitalisation risk.
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Affiliation(s)
- T. Waddell
- Department of Engineering Science, The University of Oxford, Oxford, United Kingdom
- Perspectum Ltd., Oxford, United Kingdom
| | - A. I. L. Namburete
- Department of Computer Science, University of Oxford, Oxford, United Kingdom
| | - P. Duckworth
- Oxford Robotics Institute, The University of Oxford, Oxford, United Kingdom
| | | | | | - D. J. Cuthbertson
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
| | - J. P. Despres
- Scientific director of VITAM – Research Center for Sustainable Health, Laval University, Quebec, QC, Canada
| | - M. Brady
- Perspectum Ltd., Oxford, United Kingdom
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Buchynskyi M, Kamyshna I, Oksenych V, Zavidniuk N, Kamyshnyi A. The Intersection of COVID-19 and Metabolic-Associated Fatty Liver Disease: An Overview of the Current Evidence. Viruses 2023; 15:v15051072. [PMID: 37243158 DOI: 10.3390/v15051072] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. With our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a pervasive public health concern intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and MAFLD is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among MAFLD patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of MAFLD on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.
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Affiliation(s)
- Mykhailo Buchynskyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Iryna Kamyshna
- Department of Medical Rehabilitation, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Valentyn Oksenych
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
| | - Nataliia Zavidniuk
- Department of Infectious Diseases with Epidemiology, Dermatology and Venerology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Aleksandr Kamyshnyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
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Wiesenthal AA, Legroux TM, Richter C, Junker BH, Hecksteden A, Kessler SM, Hoppstädter J, Kiemer AK. Endotoxin Tolerance Acquisition and Altered Hepatic Fatty Acid Profile in Aged Mice. BIOLOGY 2023; 12:biology12040530. [PMID: 37106731 PMCID: PMC10135800 DOI: 10.3390/biology12040530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 03/13/2023] [Accepted: 03/24/2023] [Indexed: 04/03/2023]
Abstract
(1) Background: Aging is linked to an altered immune response and metabolism. Inflammatory conditions, such as sepsis, COVID-19, and steatohepatitis are more prevalent in the elderly and steatosis is linked both to severe COVID-19 and sepsis. We hypothesized that aging is linked to a loss of endotoxin tolerance, which normally protects the host from excessive inflammation, and that this is accompanied by elevated levels of hepatic lipids. (2) Methods: An in vivo lipopolysaccharide (LPS) tolerance model in young and old mice was used and the cytokine serum levels were measured by ELISA. Cytokine and toll-like receptor gene expression was determined by qPCR in the lungs and the liver; hepatic fatty acid composition was assessed by GC–MS. (3) Results: The old mice showed a distinct potential for endotoxin tolerance as suggested by the serum cytokine levels and gene expression in the lung tissue. Endotoxin tolerance was less pronounced in the livers of the aged mice. However, the fatty acid composition strongly differed in the liver tissues of the young and old mice with a distinct change in the ratio of C18 to C16 fatty acids. (4) Conclusions: Endotoxin tolerance is maintained in advanced age, but changes in the metabolic tissue homeostasis may lead to an altered immune response in old individuals.
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Affiliation(s)
- Amanda A. Wiesenthal
- Pharmaceutical Biology, Department of Pharmacy, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany
- Marine Biology, Institute of Biological Sciences, University of Rostock, D-18059 Rostock, Germany
| | - Thierry M. Legroux
- Pharmaceutical Biology, Department of Pharmacy, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany
| | - Chris Richter
- Biosynthesis of Active Substances, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06120 Halle, Germany
| | - Björn H. Junker
- Biosynthesis of Active Substances, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06120 Halle, Germany
| | - Anne Hecksteden
- Institute of Sports and Preventive Medicine, Saarland University, D-66123 Saarbrücken, Germany
| | - Sonja M. Kessler
- Experimental Pharmacology for Natural Sciences, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06120 Halle, Germany
| | - Jessica Hoppstädter
- Pharmaceutical Biology, Department of Pharmacy, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany
| | - Alexandra K. Kiemer
- Pharmaceutical Biology, Department of Pharmacy, Saarland University, Campus C2.3, D-66123 Saarbrücken, Germany
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5
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Ippolito D, Maino C, Vernuccio F, Cannella R, Inchingolo R, Dezio M, Faletti R, Bonaffini PA, Gatti M, Sironi S. Liver involvement in patients with COVID-19 infection: A comprehensive overview of diagnostic imaging features. World J Gastroenterol 2023; 29:834-850. [PMID: 36816623 PMCID: PMC9932422 DOI: 10.3748/wjg.v29.i5.834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/06/2022] [Accepted: 01/20/2023] [Indexed: 02/06/2023] Open
Abstract
During the first wave of the pandemic, coronavirus disease 2019 (COVID-19) infection has been considered mainly as a pulmonary infection. However, different clinical and radiological manifestations were observed over time, including involvement of abdominal organs. Nowadays, the liver is considered one of the main affected abdominal organs. Hepatic involvement may be caused by either a direct damage by the virus or an indirect damage related to COVID-19 induced thrombosis or to the use of different drugs. After clinical assessment, radiology plays a key role in the evaluation of liver involvement. Ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) may be used to evaluate liver involvement. US is widely available and it is considered the first-line technique to assess liver involvement in COVID-19 infection, in particular liver steatosis and portal-vein thrombosis. CT and MRI are used as second- and third-line techniques, respectively, considering their higher sensitivity and specificity compared to US for assessment of both parenchyma and vascularization. This review aims to the spectrum of COVID-19 liver involvement and the most common imaging features of COVID-19 liver damage.
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Affiliation(s)
- Davide Ippolito
- Milano Bicocca School of Medicine and Surgery, Milano 20126, Italy
- Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Cesare Maino
- Fondazione IRCCS San Gerardo dei Tintori, Monza 20900, Italy
| | - Federica Vernuccio
- Institute of Radiology (DIMED), University Hospital of Padova, Padova 35128, Italy
| | - Roberto Cannella
- Section of Radiology-Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, Palermo 90127, Italy
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo 90127, Italy
| | - Riccardo Inchingolo
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
| | - Michele Dezio
- Division of Interventional Radiology, Department of Radiology, Madonna delle Grazie Hospital, Matera 75100, Italy
| | - Riccardo Faletti
- Department of Surgical Sciences, University of Turin, Turin 10126, Italy
| | - Pietro Andrea Bonaffini
- Milano Bicocca School of Medicine and Surgery, Milano 20126, Italy
- Department of Diagnostic Radiology, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
| | - Marco Gatti
- Department of Diagnostic Radiology, University of Turin, Turin 10126, Italy
| | - Sandro Sironi
- Milano Bicocca School of Medicine and Surgery, Milano 20126, Italy
- Department of Diagnostic Radiology, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
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Baldelli L, Marjot T, Barnes E, Barritt AS, Webb GJ, Moon AM. SARS-CoV-2 Infection and Liver Disease: A Review of Pathogenesis and Outcomes. Gut Liver 2023; 17:12-23. [PMID: 36457261 PMCID: PMC9840920 DOI: 10.5009/gnl220327] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/31/2022] [Accepted: 09/07/2022] [Indexed: 12/03/2022] Open
Abstract
The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.
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Affiliation(s)
- Luke Baldelli
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Eleanor Barnes
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Gwilym J. Webb
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Andrew M. Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
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Dietrich CG, Geier A, Merle U. Non-alcoholic fatty liver disease and COVID-19: Harmless companions or disease intensifier? World J Gastroenterol 2023; 29:367-377. [PMID: 36687116 PMCID: PMC9846932 DOI: 10.3748/wjg.v29.i2.367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 11/09/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
The pandemics of coronavirus disease 2019 (COVID-19) and non-alcoholic fatty liver disease (NAFLD) coexist. Elevated liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD, while preexisting liver damage from NAFLD may influence the course of COVID-19. However, the prognostic relevance of this interaction, though, is unclear. Obesity is a risk factor for the presence of NAFLD as well as a severe course of COVID-19. Cohort studies reveal conflicting results regarding the influence of NAFLD presence on COVID-19 illness severity. Striking molecular similarities of cytokine pathways in both diseases, including postacute sequelae of COVID-19, suggest common pathways for chronic low-activity inflammation. This review will summarize existing data regarding the interaction of both diseases and discuss possible mechanisms of the influence of one disease on the other.
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Affiliation(s)
| | - Andreas Geier
- Division of Hepatology, Department of Medicine II, University Hospital Wuerzburg, Wuerzburg 97080, Germany
| | - Uta Merle
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg 69120, Germany
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8
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Philips CA, Madhu D, Augustine P. Investigating the correlation between COVID-19 and the progression of chronic liver disease. Expert Rev Gastroenterol Hepatol 2023; 17:603-613. [PMID: 37086388 DOI: 10.1080/17474124.2023.2206564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 04/20/2023] [Indexed: 04/23/2023]
Abstract
INTRODUCTION The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.
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Affiliation(s)
- Cyriac Abby Philips
- Clinical and Translational Hepatology and The Monarch Liver Laboratory, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, Kerala, India
| | - Deepak Madhu
- Department of Gastroenterology, Lisie Hospital, Ernakulam, Kerala, India
| | - Philip Augustine
- Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, Kerala, India
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Andersson A, Kelly M, Imajo K, Nakajima A, Fallowfield JA, Hirschfield G, Pavlides M, Sanyal AJ, Noureddin M, Banerjee R, Dennis A, Harrison S. Clinical Utility of Magnetic Resonance Imaging Biomarkers for Identifying Nonalcoholic Steatohepatitis Patients at High Risk of Progression: A Multicenter Pooled Data and Meta-Analysis. Clin Gastroenterol Hepatol 2022; 20:2451-2461.e3. [PMID: 34626833 DOI: 10.1016/j.cgh.2021.09.041] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 09/22/2021] [Accepted: 09/28/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. NAFLD is associated with excess risk of all-cause mortality, and its progression to nonalcoholic steatohepatitis (NASH) and fibrosis accounts for a growing proportion of cirrhosis and hepatocellular cancer and thus is a leading cause of liver transplant worldwide. Noninvasive precise methods to identify patients with NASH and NASH with significant disease activity and fibrosis are crucial when the disease is still modifiable. The aim of this study was to examine the clinical utility of corrected T1 (cT1) vs magnetic resonance imaging (MRI) liver fat for identification of NASH participants with nonalcoholic fatty liver disease activity score ≥4 and fibrosis stage (F) ≥2 (high-risk NASH). METHODS Data from five clinical studies (n = 543) with participants suspected of NAFLD were pooled or used for individual participant data meta-analysis. The diagnostic accuracy of the MRI biomarkers to stratify NASH patients was determined using the area under the receiver operating characteristic curve (AUROC). RESULTS A stepwise increase in cT1 and MRI liver fat with increased NAFLD severity was shown, and cT1 was significantly higher in participants with high-risk NASH. The diagnostic accuracy (AUROC) of cT1 to identify patients with NASH was 0.78 (95% CI, 0.74-0.82), for liver fat was 0.78 (95% CI, 0.73-0.82), and when combined with MRI liver fat was 0.82 (95% CI, 0.78-0.85). The diagnostic accuracy of cT1 to identify patients with high-risk NASH was good (AUROC = 0.78; 95% CI, 0.74-0.82), was superior to MRI liver fat (AUROC = 0.69; 95% CI, 0.64-0.74), and was not substantially improved by combining it with MRI liver fat (AUROC = 0.79; 95% CI, 0.75-0.83). The meta-analysis showed similar performance to the pooled analysis for these biomarkers. CONCLUSIONS This study shows that quantitative MRI-derived biomarkers cT1 and liver fat are suitable for identifying patients with NASH, and cT1 is a better noninvasive technology than liver fat to identify NASH patients at greatest risk of disease progression. Therefore, MRI cT1 and liver fat have important clinical utility to help guide the appropriate use of interventions in NAFLD and NASH clinical care pathways.
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Affiliation(s)
| | - Matt Kelly
- Perspectum Ltd, Gemini One, Oxford, United Kingdom
| | - Kento Imajo
- Department of Gastroenterology and Hepatology, Yokohama City School of Medicine, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City School of Medicine, Yokohama, Japan
| | | | - Gideon Hirschfield
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| | - Michael Pavlides
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, United Kingdom; National Institute for Health Research (NIHR) Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
| | - Arun J Sanyal
- Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virgina
| | - Mazen Noureddin
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Cedars Sinai Medical Center, Los Angeles, California
| | | | | | - Stephen Harrison
- Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom
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Chen H, Chen Q. COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD. Int J Biol Sci 2022; 18:4756-4767. [PMID: 35874945 PMCID: PMC9305262 DOI: 10.7150/ijbs.72461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 06/23/2022] [Indexed: 01/08/2023] Open
Abstract
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world's adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.
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Affiliation(s)
- Hanfei Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
| | - Qiang Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,MOE Frontier Science Centre for Precision Oncology, University of Macau, Taipa, Macau SAR, China
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11
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Papic N, Samadan L, Vrsaljko N, Radmanic L, Jelicic K, Simicic P, Svoboda P, Lepej SZ, Vince A. Distinct Cytokine Profiles in Severe COVID-19 and Non-Alcoholic Fatty Liver Disease. Life (Basel) 2022; 12:life12060795. [PMID: 35743825 PMCID: PMC9225218 DOI: 10.3390/life12060795] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 05/15/2022] [Accepted: 05/24/2022] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is identified as a risk factor for developing severe COVID-19. While NAFLD is associated with chronic low-grade inflammation, mechanisms leading to immune system hyperactivation remain unclear. The aim of this prospective observational study is to analyze cytokine profiles in patients with severe COVID-19 and NAFLD. A total of 94 patients with severe COVID-19 were included. Upon admission, clinical and laboratory data were collected, a liver ultrasound was performed to determine the presence of steatosis, and subsequently, 51 were diagnosed with NAFLD according to the current guidelines. There were no differences in age, sex, comorbidities, and baseline disease severity between the groups. Serum cytokine concentrations were analyzed using a multiplex bead-based assay by flow cytometry. Upon admission, the NAFLD group had higher C-reactive protein, procalcitonin, alanine aminotransferase, lactate dehydrogenase, and fibrinogen. Interleukins-6, -8, and -10 and CXCL10 were significantly higher, while IFN-γ was lower in NAFLD patients. Patients with NAFLD who progressed to critical illness had higher concentrations of IL-6, -8, -10, and IFN-β, and IL-8 and IL-10 appear to be effective prognostic biomarkers associated with time to recovery. In conclusion, NAFLD is associated with distinct cytokine profiles in COVID-19, possibly associated with disease severity and adverse outcomes.
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Affiliation(s)
- Neven Papic
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.S.); (A.V.)
- Department for Viral Hepatitis, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia; (N.V.); (K.J.)
- Correspondence:
| | - Lara Samadan
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.S.); (A.V.)
| | - Nina Vrsaljko
- Department for Viral Hepatitis, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia; (N.V.); (K.J.)
| | - Leona Radmanic
- Department for Clinical Immunology and Molecular Diagnostics, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia; (L.R.); (P.S.); (S.Z.L.)
| | - Karlo Jelicic
- Department for Viral Hepatitis, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia; (N.V.); (K.J.)
| | - Petra Simicic
- Department for Clinical Immunology and Molecular Diagnostics, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia; (L.R.); (P.S.); (S.Z.L.)
| | - Petra Svoboda
- Research Department, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia;
| | - Snjezana Zidovec Lepej
- Department for Clinical Immunology and Molecular Diagnostics, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia; (L.R.); (P.S.); (S.Z.L.)
- Department of Biology, Faculty of Science, University of Zagreb, 10000 Zagreb, Croatia
| | - Adriana Vince
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.S.); (A.V.)
- Department for Viral Hepatitis, University Hospital for Infectious Diseases, 10000 Zagreb, Croatia; (N.V.); (K.J.)
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Radzina M, Putrins DS, Micena A, Vanaga I, Kolesova O, Platkajis A, Viksna L. Post-COVID-19 Liver Injury: Comprehensive Imaging With Multiparametric Ultrasound. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2022; 41:935-949. [PMID: 34241914 PMCID: PMC8427044 DOI: 10.1002/jum.15778] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 05/14/2021] [Indexed: 05/03/2023]
Abstract
OBJECTIVES This study aimed to define patterns of liver injury after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using multiparametric ultrasound (mpUS) in a variable patient population with differing severities of COVID-19. METHODS Ninety patients were enrolled into the study: 56 had SARS-CoV-2 3-9 months prior to enrolment; 34 served as a clinically healthy control group. All patients underwent an mpUS evaluation of the liver (elastography, dispersion and attenuation imaging). Seventy-six patients had abdominal magnetic resonance (MR) and noncontrast enhanced thoracic computed tomography (CT) scans performed at the same day. All patients were screened for biochemical markers of liver injury. RESULTS Liver elasticity, viscosity, and steatosis values were significantly altered in patients after COVID-19, with particularly higher fibrosis scores compared to the control group (P < .001). Increased biochemical markers of liver injury correlated with changes in mpUS (P < .05), but not with findings on CT or MR findings. Seventeen of 34 hospitalized patients had a moderate or severe course of the disease course with more pronounced changes in mpUS. Increased body mass index was found to influence liver injury and correlated with more severe forms of COVID-19 (P < .001). CONCLUSIONS COVID-19 can cause liver injury observable using mpUS. More severe forms of COVID-19 and patient obesity are related to increased values of liver damage observed. In comparison to MRI and CT, mpUS appears to be more sensitive to involvement of liver parenchyma. Further research is warranted to establish this promising method for evaluating post-COVID-19 liver involvement in the aftermath of the pandemic.
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Affiliation(s)
- Maija Radzina
- Institute of Diagnostic RadiologyPauls Stradins Clinical University HospitalRigaLatvia
- Radiology Research LaboratoryRīga Stradiņš UniversityRigaLatvia
- Faculty of MedicineUniversity of LatviaRigaLatvia
| | - Davis Simanis Putrins
- Institute of Diagnostic RadiologyPauls Stradins Clinical University HospitalRigaLatvia
- Faculty of MedicineUniversity of LatviaRigaLatvia
| | - Arta Micena
- Institute of Diagnostic RadiologyPauls Stradins Clinical University HospitalRigaLatvia
- Faculty of MedicineUniversity of LatviaRigaLatvia
| | - Ieva Vanaga
- Department of InfectologyRīga Stradiņš UniversityRigaLatvia
- Joint Laboratory of Immunology and ImmunogeneticsRīga Stradiņš UniversityRigaLatvia
- Riga East Clinical University HospitalRigaLatvia
| | - Oksana Kolesova
- Department of InfectologyRīga Stradiņš UniversityRigaLatvia
- Joint Laboratory of Immunology and ImmunogeneticsRīga Stradiņš UniversityRigaLatvia
| | - Ardis Platkajis
- Riga East Clinical University HospitalRigaLatvia
- Department of RadiologyRīga Stradiņš UniversityRigaLatvia
| | - Ludmila Viksna
- Department of InfectologyRīga Stradiņš UniversityRigaLatvia
- Riga East Clinical University HospitalRigaLatvia
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Colca JR, Scherer PE. The metabolic syndrome, thiazolidinediones, and implications for intersection of chronic and inflammatory disease. Mol Metab 2022; 55:101409. [PMID: 34863942 PMCID: PMC8688722 DOI: 10.1016/j.molmet.2021.101409] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 11/24/2021] [Accepted: 11/27/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Chronic disease appears connected to obesity. However, evidence suggests that chronic metabolic diseases are more specifically related to adipose dysfunction rather than to body weight itself. SCOPE OF REVIEW Further study of the first generation "insulin sensitizer" pioglitazone and molecules based on its structure suggests that is possible to decouple body weight from the metabolic dysfunction that drives adverse outcomes. The growing understanding of the mechanism of action of these agents together with advances in the pathophysiology of chronic metabolic disease offers a new approach to treat chronic conditions, such as type 2 diabetes, fatty liver disease, and their common organ and vascular sequelae. MAJOR CONCLUSIONS We hypothesize that treating adipocyte dysfunction with new insulin sensitizers might significantly impact the interface of infectious disease and chronic metabolic disease.
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Affiliation(s)
- Jerry R Colca
- Department of Biomedical Sciences, Western Michigan University School of Medicine, Kalamazoo, MI 49008, USA; Cirius Therapeutics, Kalamazoo, MI 49007, USA
| | - Philipp E Scherer
- Touchstone Diabetes Center, Department of Internal Medicine, USA; Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA.
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14
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Anirvan P, Singh SP, Giammarino A, Satapathy SK. Association of non-alcoholic fatty liver disease and COVID-19: A literature review of current evidence. World J Hepatol 2021; 13:916-925. [PMID: 34552698 PMCID: PMC8422920 DOI: 10.4254/wjh.v13.i8.916] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/21/2021] [Accepted: 08/04/2021] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has swept through nations, crippled economies and caused millions of deaths worldwide. Many people diagnosed with COVID-19 infections are often found to develop liver injury, which, in a small portion of patients, progresses to severe liver disease. Liver injury in the form of elevated transaminases, hyperbilirubinemia and alterations in serum albumin has been observed to be higher in patients with severe forms of the disease. Those who already have insult to the liver from chronic disease, such as nonalcoholic fatty liver disease (NAFLD) may be at the greatest disadvantage. The severity of COVID-19 also seems to be driven by the presence of NAFLD and other co-morbidities. About 25% of the global population has NAFLD. With such a widespread prevalence of NAFLD, understanding the disease progression of COVID-19 and the occurrence of liver injury in this vulnerable population assumes great significance. In this review, we present an overview of COVID-19 infection in patients with NAFLD.
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Affiliation(s)
- Prajna Anirvan
- Department of Gastroenterology, Sriram Chandra Bhanj Medical College and Hospital, Cuttack 753007, Odisha, India
| | - Shivaram P Singh
- Department of Gastroenterology, Sriram Chandra Bhanj Medical College and Hospital, Cuttack 753007, Odisha, India
| | - Alexa Giammarino
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra, Manhasset, NY 11030, United States
| | - Sanjaya K Satapathy
- Division of Hepatology at Sandra Atlas Bass Center for Liver Diseases and Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra, Manhasset, NY 11030, United States.
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