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Horm Metab Res 2022; 54(08): 522-531
DOI: 10.1055/a-1834-9008
Review

Liver, NAFLD and COVID-19

Carlotta Hoffmann
1   University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
,
Philipp A. Gerber
2   University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland, Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland
,
Claudia Cavelti-Weder
2   University Hospital Zurich (USZ) and University of Zurich (UZH), Switzerland, Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland
,
Louisa Licht
1   University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
,
Reham Kotb
3   Abu Dhabi University, Abu Dhabi, United Arab Emirates, College of Health Sciences, Abu Dhabi, United Arab Emirates
,
Rania Al Dweik
4   Abu Dhabi University, Abu Dhabi, United Arab Emirates, Department of Public Health, Abu Dhabi, United Arab Emirates
,
Michele Cherfane
3   Abu Dhabi University, Abu Dhabi, United Arab Emirates, College of Health Sciences, Abu Dhabi, United Arab Emirates
,
Stefan R. Bornstein
1   University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
,
Nikolaos Perakakis
1   University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany, Department of Internal Medicine III, Dresden, Germany
5   University Hospital and Faculty of Medicine, TU Dresden, Dresden, Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, Dresden, Germany
6   Neuherberg, German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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Abstract

Coronavirus disease 2019 (COVID-19) is characterized by a wide clinical spectrum that includes abnormalities in liver function indicative of liver damage. Conversely, people with liver diseases are at higher risk of severe COVID-19. In the current review, we summarize first the epidemiologic evidence describing the bidirectional relationship between COVID-19 and liver function/liver diseases. Additionally, we present the most frequent histologic findings as well as the most important direct and indirect mechanisms supporting a COVID-19 mediated liver injury. Furthermore, we focus on the most frequent liver disease in the general population, non-alcoholic or metabolic-associated fatty liver disease (NAFLD/MAFLD), and describe how COVID-19 may affect NAFLD/MAFLD development and progression and conversely how NAFLD/MAFLD may further aggravate a COVID-19 infection. Finally, we present the long-term consequences of the pandemic on the development and management of NAFLD.

Key words

NAFLD - COVID-19 - MAFLD - SARS-CoV-2 - liver


Publication History

Received: 17 March 2022

Accepted after revision: 25 April 2022

Accepted Manuscript online:
25 April 2022

Article published online:
14 June 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Younossi ZM, Koenig AB, Abdelatif D. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64: 73-84
    CrossrefPubMedGoogle Scholar
  • 2 Younossi Z, Anstee QM, Marietti M. et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2018; 15: 11-20
    Google Scholar
  • 3 Singh A, Hussain S, Antony B. Non-alcoholic fatty liver disease and clinical outcomes in patients with COVID-19: A comprehensive systematic review and meta-analysis. Diabetes Metab Syndr 2021; 15: 813-822
    CrossrefPubMedGoogle Scholar
  • 4 Tao Z, Li Y, Cheng B. et al. Risk of severe COVID-19 increased by metabolic dysfunction-associated fatty liver disease: a meta-analysis. J Clin Gastroenterol 2021; 55: 830-835
    CrossrefPubMedGoogle Scholar
  • 5 Targher G, Mantovani A, Byrne CD. et al. Risk of severe illness from COVID-19 in patients with metabolic dysfunction-associated fatty liver disease and increased fibrosis scores. Gut 2020; 69: 1545-1547
    CrossrefPubMedGoogle Scholar
  • 6 Targher G, Mantovani A, Byrne CD. et al. Detrimental effects of metabolic dysfunction-associated fatty liver disease and increased neutrophil-to-lymphocyte ratio on severity of COVID-19. Diabetes Metab 2020; 46: 505-507
    CrossrefPubMedGoogle Scholar
  • 7 Zhao X, Lei Z, Gao F. et al. The impact of coronavirus disease 2019 (COVID-19) on liver injury in China: a systematic review and meta-analysis. Medicine (Baltimore) 2021; 100: e24369
    CrossrefPubMedGoogle Scholar
  • 8 Del Zompo F, De Siena M, Ianiro G. et al. Prevalence of liver injury and correlation with clinical outcomes in patients with COVID-19: systematic review with meta-analysis. Eur Rev Med Pharmacol Sci 2020; 24: 13072-13088
    PubMedGoogle Scholar
  • 9 Sultan S, Altayar O, Siddique SM. et al. AGA institute rapid review of the gastrointestinal and liver manifestations of COVID-19, meta-analysis of international data, and recommendations for the consultative management of patients with COVID-19. Gastroenterology 2020; 159: 320-334 e27
    CrossrefPubMedGoogle Scholar
  • 10 Cai Q, Huang D, Yu H. et al. COVID-19: Abnormal liver function tests. J Hepatol 2020; 73: 566-574
    CrossrefPubMedGoogle Scholar
  • 11 Piano S, Dalbeni A, Vettore E. et al. Abnormal liver function tests predict transfer to intensive care unit and death in COVID-19. Liver Int 2020; 40: 2394-2406
    CrossrefPubMedGoogle Scholar
  • 12 Zhang Y, Zheng L, Liu L. et al. Liver impairment in COVID-19 patients: a retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int 2020; 40: 2095-2103
    CrossrefPubMedGoogle Scholar
  • 13 Shi C, Wang L, Ye J. et al. Predictors of mortality in patients with coronavirus disease 2019: a systematic review and meta-analysis. BMC Infect Dis 2021; 21: 663
    CrossrefPubMedGoogle Scholar
  • 14 Bende F, Tudoran C, Sporea I. et al. A multidisciplinary approach to evaluate the presence of hepatic and cardiac abnormalities in patients with post-acute COVID-19 syndrome-A pilot study. J Clin Med 2021; 10: 2507
    CrossrefPubMedGoogle Scholar
  • 15 Roth NC, Kim A, Vitkovski T. et al. Post-COVID-19 cholangiopathy: a novel entity. Am J Gastroenterol 2021; 116: 1077-1082
    CrossrefPubMedGoogle Scholar
  • 16 Durazo FA, Nicholas AA, Mahaffey JJ. et al. Post-covid-19 cholangiopathy – a new indication for liver transplantation: a case report. Transplant Proc 2021; 53: 1132-1137
    CrossrefPubMedGoogle Scholar
  • 17 Lee A, Wein AN, Doyle MBM. et al. Liver transplantation for post-COVID-19 sclerosing cholangitis. BMJ Case Rep 2021; 14: e244168
    CrossrefPubMedGoogle Scholar
  • 18 Ji D, Qin E, Xu J. et al. Non-alcoholic fatty liver diseases in patients with COVID-19: a retrospective study. J Hepatol 2020; 73: 451-453
    CrossrefPubMedGoogle Scholar
  • 19 Forlano R, Mullish BH, Mukherjee SK. et al. In-hospital mortality is associated with inflammatory response in NAFLD patients admitted for COVID-19. PLoS One 2020; 15: e0240400
    CrossrefPubMedGoogle Scholar
  • 20 Bramante C, Tignanelli CJ, Dutta N. et al. Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for Covid-19. medRxiv 2020; 2020.09.01.20185850 DOI: 10.1101/2020.09.01.20185850 Preprint.
    CrossrefPubMedGoogle Scholar
  • 21 Gao F, Zheng KI, Yan HD. et al. Association and interaction between serum interleukin-6 levels and metabolic dysfunction-associated fatty liver disease in patients with severe coronavirus disease 2019. Front Endocrinol (Lausanne) 2021; 12: 604100
    CrossrefPubMedGoogle Scholar
  • 22 Middleton P, Hsu C, Lythgoe MP. Clinical outcomes in COVID-19 and cirrhosis: a systematic review and meta-analysis of observational studies. BMJ Open Gastroenterol 2021; 8: e000739
    CrossrefPubMedGoogle Scholar
  • 23 Belli LS, Duvoux C, Cortesi PA. et al. COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes – an ELITA/ELTR multicentre cohort study. Gut 2021; 70: 1914-1924
    CrossrefPubMedGoogle Scholar
  • 24 Diaz LA, Idalsoaga F, Cannistra M. et al. High prevalence of hepatic steatosis and vascular thrombosis in COVID-19: a systematic review and meta-analysis of autopsy data. World J Gastroenterol 2020; 26: 7693-7706
    CrossrefPubMedGoogle Scholar
  • 25 Chu H, Peng L, Hu L. et al. Liver histopathological analysis of 24 postmortem findings of patients with COVID-19 in China. Front Med (Lausanne) 2021; 8: 749318
    CrossrefPubMedGoogle Scholar
  • 26 Brunt EM, Tiniakos DG. Histopathology of nonalcoholic fatty liver disease. World J Gastroenterol 2010; 16: 5286-5296
    CrossrefPubMedGoogle Scholar
  • 27 Brunt EM, Neuschwander-Tetri BA, Oliver D. et al. Nonalcoholic steatohepatitis: histologic features and clinical correlations with 30 blinded biopsy specimens. Hum Pathol 2004; 35: 1070-1082
    CrossrefPubMedGoogle Scholar
  • 28 Cortez-Pinto H, Baptista A, Camilo ME. Hepatic stellate cell activation occurs in nonalcoholic steatohepatitis. Hepatogastroenterology 2001; 48: 87-90
    PubMedGoogle Scholar
  • 29 Jackson CB, Farzan M, Chen B. et al. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 2022; 23: 3-20
    CrossrefPubMedGoogle Scholar
  • 30 Williams TL, Strachan G, Macrae RGC. et al. Differential expression in humans of the viral entry receptor ACE2 compared with the short deltaACE2 isoform lacking SARS-CoV-2 binding sites. Sci Rep 2021; 11: 24336
    CrossrefPubMedGoogle Scholar
  • 31 Pirola CJ, Sookoian S. SARS-CoV-2 virus and liver expression of host receptors: Putative mechanisms of liver involvement in COVID-19. Liver Int 2020; 40: 2038-2040
    CrossrefPubMedGoogle Scholar
  • 32 Meijnikman AS, Bruin S, Groen AK. et al. Increased expression of key SARS-CoV-2 entry points in multiple tissues in individuals with NAFLD. J Hepatol 2021; 74: 748-749
    CrossrefPubMedGoogle Scholar
  • 33 Cantuti-Castelvetri L, Ojha R, Pedro LD. et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 2020; 370: 856-860
    CrossrefPubMedGoogle Scholar
  • 34 Daly JL, Simonetti B, Klein K. et al. Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science 2020; 370: 861-865
    CrossrefPubMedGoogle Scholar
  • 35 Benedicto A, Garcia-Kamiruaga I, Arteta B. Neuropilin-1: A feasible link between liver pathologies and COVID-19. World J Gastroenterol 2021; 27: 3516-3529
    CrossrefPubMedGoogle Scholar
  • 36 Cao S, Yaqoob U, Das A. et al. Neuropilin-1 promotes cirrhosis of the rodent and human liver by enhancing PDGF/TGF-beta signaling in hepatic stellate cells. J Clin Invest 2010; 120: 2379-2394
    CrossrefPubMedGoogle Scholar
  • 37 Elpek GO. Neuropilins and liver. World J Gastroenterol 2015; 21: 7065-7073
    CrossrefPubMedGoogle Scholar
  • 38 Puelles VG, Lutgehetmann M, Lindenmeyer MT. et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020; 383: 590-592
    CrossrefPubMedGoogle Scholar
  • 39 Sonzogni A, Previtali G, Seghezzi M. et al. Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations. Liver Int 2020; 40: 2110-2116
    CrossrefPubMedGoogle Scholar
  • 40 Wang Y, Liu S, Liu H. et al. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol 2020; 73: 807-816
    CrossrefPubMedGoogle Scholar
  • 41 Lagana SM, Kudose S, Iuga AC. et al. Hepatic pathology in patients dying of COVID-19: a series of 40 cases including clinical, histologic, and virologic data. Mod Pathol 2020; 33: 2147-2155
    CrossrefPubMedGoogle Scholar
  • 42 Nuovo GJ, Suster D, Awad H. et al. The histologic and molecular correlates of liver disease in fatal COVID-19 including with alcohol use disorder. Ann Diagn Pathol 2022; 57: 151881
    CrossrefPubMedGoogle Scholar
  • 43 Nardo AD, Schneeweiss-Gleixner M, Bakail M. et al. Pathophysiological mechanisms of liver injury in COVID-19. Liver Int 2021; 41: 20-32
    CrossrefPubMedGoogle Scholar
  • 44 Perakakis N, Stefanakis K, Mantzoros CS. The role of omics in the pathophysiology, diagnosis and treatment of non-alcoholic fatty liver disease. Metabolism Clin Exp 2020; 111S: 154320
    CrossrefPubMedGoogle Scholar
  • 45 Donnelly KL, Smith CI, Schwarzenberg SJ. et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115: 1343-1351
    CrossrefPubMedGoogle Scholar
  • 46 Shimano H, Sato R. SREBP-regulated lipid metabolism: convergent physiology – divergent pathophysiology. Nat Rev Endocrinol 2017; 13: 710-730
    CrossrefPubMedGoogle Scholar
  • 47 Koek GH, Liedorp PR, Bast A. The role of oxidative stress in non-alcoholic steatohepatitis. Clin Chim Acta 2011; 412: 1297-1305
    CrossrefPubMedGoogle Scholar
  • 48 Robles JP, Zamora M, Adan-Castro E. et al. The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin alpha5beta1 and NF-kappaB signaling. J Biol Chem 2022; 298: 101695
    CrossrefPubMedGoogle Scholar
  • 49 Idalsoaga F, Ayares G, Arab JP. et al. COVID-19 and Indirect Liver Injury: A Narrative Synthesis of the Evidence. J Clin Transl Hepatol 2021; 9: 760-768
    PubMedGoogle Scholar
  • 50 McConnell MJ, Kawaguchi N, Kondo R. et al. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. J Hepatol 2021; 75: 647-658
    CrossrefPubMedGoogle Scholar
  • 51 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506
    Google Scholar
  • 52 Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol 2017; 66: 1300-1312
    CrossrefPubMedGoogle Scholar
  • 53 Osawa Y, Kojika E, Hayashi Y. et al. Tumor necrosis factor-alpha-mediated hepatocyte apoptosis stimulates fibrosis in the steatotic liver in mice. Hepatol Commun 2018; 2: 407-420
    CrossrefPubMedGoogle Scholar
  • 54 Hou X, Yin S, Ren R. et al. Myeloid-cell-specific IL-6 signaling promotes microRNA-223-enriched exosome production to attenuate NAFLD-associated fibrosis. Hepatology 2021; 74: 116-132
    CrossrefPubMedGoogle Scholar
  • 55 Akhmerov A, Marban E. COVID-19 and the heart. Circ Res 2020; 126: 1443-1455
    CrossrefPubMedGoogle Scholar
  • 56 Horvatits T, Drolz A, Trauner M. et al. Liver injury and failure in critical illness. Hepatology 2019; 70: 2204-2215
    CrossrefPubMedGoogle Scholar
  • 57 Xie C, Yagai T, Luo Y. et al. Activation of intestinal hypoxia-inducible factor 2alpha during obesity contributes to hepatic steatosis. Nat Med 2017; 23: 1298-1308
    CrossrefPubMedGoogle Scholar
  • 58 Wang X, de Carvalho Ribeiro M, Iracheta-Vellve A. et al. Macrophage-specific hypoxia-inducible factor-1alpha contributes to impaired autophagic flux in nonalcoholic steatohepatitis. Hepatology 2019; 69: 545-563
    CrossrefPubMedGoogle Scholar
  • 59 Chen J, Chen J, Fu H. et al. Hypoxia exacerbates nonalcoholic fatty liver disease via the HIF-2alpha/PPARalpha pathway. Am J Physiol Endocrinol Metab 2019; 317: E710-E722
    CrossrefPubMedGoogle Scholar
  • 60 Chen J, Chen J, Huang J. et al. HIF-2alpha upregulation mediated by hypoxia promotes NAFLD-HCC progression by activating lipid synthesis via the PI3K-AKT-mTOR pathway. Aging (Albany NY) 2019; 11: 10839-10860
    CrossrefPubMedGoogle Scholar
  • 61 Qu A, Taylor M, Xue X. et al. Hypoxia-inducible transcription factor 2alpha promotes steatohepatitis through augmenting lipid accumulation, inflammation, and fibrosis. Hepatology 2011; 54: 472-483
    CrossrefPubMedGoogle Scholar
  • 62 Kulkarni AV, Kumar P, Tevethia HV. et al. Systematic review with meta-analysis: liver manifestations and outcomes in COVID-19. Aliment Pharmacol Ther 2020; 52: 584-599
    CrossrefPubMedGoogle Scholar
  • 63 Beigel JH, Tomashek KM, Dodd LE. et al. Remdesivir for the treatment of Covid-19 – final report. N Engl J Med 2020; 383: 1813-1826
    Google Scholar
  • 64 Cao B, Wang Y, Wen D. et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020; 382: 1787-1799
    Google Scholar
  • 65 Sato K, Yamazaki Y, Uraoka T. Strategy for the control of drug-induced liver injury due to investigational treatments/drugs for COVID-19. World J Gastroenterol 2021; 27: 8370-8373
    CrossrefPubMedGoogle Scholar
  • 66 Group RC. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397: 1637-1645
    CrossrefPubMedGoogle Scholar
  • 67 Guaraldi G, Meschiari M, Cozzi-Lepri A. et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol 2020; 2: e474-e484
    CrossrefPubMedGoogle Scholar
  • 68 Muhovic D, Bojovic J, Bulatovic A. et al. First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19. Liver Int 2020; 40: 1901-1905
    CrossrefPubMedGoogle Scholar
  • 69 Wong GL, Wong VW, Thompson A. et al. Management of patients with liver derangement during the COVID-19 pandemic: an Asia-Pacific position statement. . Lancet Gastroenterol Hepatol 2020; 5: 776-787
    CrossrefPubMedGoogle Scholar
  • 70 Marconi VC, Ramanan AV, de Bono S. et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet. Respir Med 2021; 9: 1407-1418
    PubMedGoogle Scholar
  • 71 Raschi E, Caraceni P, Poluzzi E. et al. Baricitinib, JAK inhibitors and liver injury: a cause for concern in COVID-19?. Expert Opin Drug Saf 2020; 19: 1367-1369
    CrossrefPubMedGoogle Scholar
  • 72 Delgado A, Stewart S, Urroz M. et al. Characterisation of drug-induced liver injury in patients with COVID-19 detected by a proactive pharmacovigilance program from laboratory signals. J Clin Med 2021; 10: 4432
    CrossrefPubMedGoogle Scholar
  • 73 Allard J, Le Guillou D, Begriche K. et al. Drug-induced liver injury in obesity and nonalcoholic fatty liver disease. Adv Pharmacol 2019; 85: 75-107
    CrossrefPubMedGoogle Scholar
  • 74 Michaut A, Moreau C, Robin MA. et al. Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease. Liver Int 2014; 34: e171-e179
    CrossrefPubMedGoogle Scholar
  • 75 Tarantino G, Conca P, Basile V. et al. A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease. Hepatol Res 2007; 37: 410-415
    CrossrefPubMedGoogle Scholar
  • 76 Zuo T, Liu Q, Zhang F. et al. Temporal landscape of human gut RNA and DNA virome in SARS-CoV-2 infection and severity. Microbiome 2021; 9: 91
    CrossrefPubMedGoogle Scholar
  • 77 Yeoh YK, Zuo T, Lui GC. et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 2021; 70: 698-706
    CrossrefPubMedGoogle Scholar
  • 78 Zuo T, Wu X, Wen W. et al. Gut microbiome alterations in COVID-19. Genom Proteom Bioinform 2021; S1672-0229(21)00206-0 DOI: 10.1016/j.gpb.2021.09.004 Online ahead of print.
    CrossrefPubMedGoogle Scholar
  • 79 Zuo T, Zhang F, Lui GCY. et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020; 159: 944-55 e8
    CrossrefPubMedGoogle Scholar
  • 80 Zuo T, Zhan H, Zhang F. et al. Alterations in fecal fungal microbiome of patients with COVID-19 during time of hospitalization until discharge. Gastroenterology 2020; 159: 1302-10 e5
    CrossrefPubMedGoogle Scholar
  • 81 Kolodziejczyk AA, Zheng D, Shibolet O. et al. The role of the microbiome in NAFLD and NASH. EMBO Mol Med 2019; 11: e9302
    CrossrefPubMedGoogle Scholar
  • 82 Adenote A, Dumic I, Madrid C. et al. NAFLD and infection, a nuanced relationship. Can J Gastroenterol Hepatol. 2021 5556354.
    PubMedGoogle Scholar
  • 83 Mahamat-Saleh Y, Fiolet T. Rebeaud MEet al. Diabetes, hypertension, body mass index, smoking and COVID-19-related mortality: a systematic review and meta-analysis of observational studies. BMJ Open 2021; 11: e052777
    Google Scholar
  • 84 Heidarpour M, Abhari AP, Sadeghpour N. et al. Prediabetes and COVID-19 severity, an underestimated risk factor: a systematic review and meta-analysis. Diabetes Metab Syndr 2021; 15: 102307
    CrossrefPubMedGoogle Scholar
  • 85 Kumar A, Arora A, Sharma P. et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab Syndr 2020; 14: 535-545
    CrossrefPubMedGoogle Scholar
  • 86 Sahni S, Gupta G, Sarda R. et al. Impact of metabolic and cardiovascular disease on COVID-19 mortality: a systematic review and meta-analysis. Diabetes Metab Syndr 2021; 15: 102308
    CrossrefPubMedGoogle Scholar
  • 87 Kim NH, Kim KJ, Choi J. et al. Metabolically unhealthy individuals, either with obesity or not, have a higher risk of critical coronavirus disease 2019 outcomes than metabolically healthy individuals without obesity. Metabolism 2022; 128: 154894
    CrossrefPubMedGoogle Scholar
  • 88 Xiao F, Zhou YC, Zhang MB. et al. Hyperglycemia and blood glucose deterioration are risk factors for severe COVID-19 with diabetes: a two-center cohort study. J Med Virol 2022; 94: 1967-1975
    CrossrefPubMedGoogle Scholar
  • 89 Eskenazi B, Rauch S, Iurlaro E. et al. Diabetes mellitus, maternal adiposity, and insulin-dependent gestational diabetes are associated with COVID-19 in pregnancy: the INTERCOVID study. Am J Obstet Gynecol 2021; DOI: 10.1016/j.ajog.2021.12.032. [Epub ahead of print]
    CrossrefPubMedGoogle Scholar
  • 90 Nseir W, Taha H, Khateeb J. et al. Fatty liver is associated with recurrent bacterial infections independent of metabolic syndrome. Dig Dis Sci 2011; 56: 3328-3334
    CrossrefPubMedGoogle Scholar
  • 91 Wang PW, Hsieh CJ, Psang LC. et al. Fatty liver and chronic inflammation in Chinese adults. Diabetes Res Clin Pract 2008; 81: 202-208
    CrossrefPubMedGoogle Scholar
  • 92 Braunersreuther V, Viviani GL, Mach F. et al. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J Gastroenterol 2012; 18: 727-735
    CrossrefPubMedGoogle Scholar
  • 93 Kazankov K, Jorgensen SMD, Thomsen KL. et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Nat Rev Gastroenterol Hepatol 2019; 16: 145-159
    CrossrefPubMedGoogle Scholar
  • 94 Song X, Hu W, Yu H. et al. Little to no expression of angiotensin-converting enzyme-2 on most human peripheral blood immune cells but highly expressed on tissue macrophages. Cytometry A 2020; DOI: 10.1002/cyto.a.24285. Online ahead of print
    CrossrefPubMedGoogle Scholar
  • 95 Tripodi A, Fracanzani AL. Primignani Met al. Procoagulant imbalance in patients with non-alcoholic fatty liver disease. J Hepatol 2014; 61: 148-154
    CrossrefPubMedGoogle Scholar
  • 96 Verrijken A, Francque S, Mertens I. et al. Prothrombotic factors in histologically proven nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology 2014; 59: 121-129
    CrossrefPubMedGoogle Scholar
  • 97 Ji D, Cheng G, Lau G. Reply to: “NAFLD is a predictor of liver injury in COVID-19 hospitalized patients but not of mortality, disease severity on the presentation or progression – The debate continues”. J Hepatol 2021; 74: 484-485
    CrossrefPubMedGoogle Scholar
  • 98 Vrsaljko N, Samadan L, Viskovic K. et al. Association of nonalcoholic fatty liver disease with COVID-19 severity and pulmonary thrombosis: CovidFAT, a prospective, observational cohort study. Open Forum Infect Dis 2022; 9 ofac073
    PubMedGoogle Scholar
  • 99 Klein OL, Krishnan JA, Glick S. et al. Systematic review of the association between lung function and Type 2 diabetes mellitus. Diabet Med 2010; 27: 977-987
    CrossrefPubMedGoogle Scholar
  • 100 Zheng H, Wu J, Jin Z. et al. Potential biochemical mechanisms of lung injury in diabetes. Aging Dis 2017; 8: 7-16
    CrossrefPubMedGoogle Scholar
  • 101 Zhou Y, Chi J, Lv W. et al. Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (Covid-19). Diabetes Metab Res Rev 2021; 37: e3377
    CrossrefPubMedGoogle Scholar
  • 102 Simon TG, Roelstraete B, Hagstrom H. et al. Non-alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort. Gut 2021; gutjnl 2021-325724 DOI: 10.1136/gutjnl-2021-325724 Online ahead of print.
    CrossrefPubMedGoogle Scholar
  • 103 Steenblock C, Schwarz PEH, Ludwig B. et al. COVID-19 and metabolic disease: mechanisms and clinical management. Lancet Diabetes Endocrinol 2021; 9: 786-798
    CrossrefPubMedGoogle Scholar
  • 104 Ammar A, Brach M, Trabelsi K. et al. Effects of COVID-19 home confinement on eating behaviour and physical activity: results of the ECLB-COVID19 international online survey. Nutrients 2020; 12: 1583 DOI: 10.3390/nu12061583.
    CrossrefPubMedGoogle Scholar
  • 105 Rowlands AV, Henson JJ, Coull NA. et al. The impact of COVID-19 restrictions on accelerometer-assessed physical activity and sleep in individuals with type 2 diabetes. Diabet Med 2021; 38: e14549
    CrossrefPubMedGoogle Scholar
  • 106 Ruissen MM, Regeer H, Landstra CP. et al. Increased stress, weight gain and less exercise in relation to glycemic control in people with type 1 and type 2 diabetes during the COVID-19 pandemic. BMJ Open Diabetes Res Care 2021; 9: e002035
    CrossrefPubMedGoogle Scholar
  • 107 Fujii H, Nakamura N, Fukumoto S. et al. Lifestyle changes during the coronavirus disease 2019 pandemic impact metabolic dysfunction-associated fatty liver disease. Liver Int 2022; 42: 995-1004
    CrossrefPubMedGoogle Scholar
  • 108 Kim RG, Medina SP, Magee C. et al. Fatty liver and the Coronavirus disease 2019 pandemic: health behaviors, social factors, and telemedicine satisfaction in vulnerable populations. Hepatol Commun 2022; 6: 1045-1055
    CrossrefPubMedGoogle Scholar
  • 109 Chudasama YV, Gillies CL, Zaccardi F. et al. Impact of COVID-19 on routine care for chronic diseases: A global survey of views from healthcare professionals. Diabetes Metab Syndr 2020; 14: 965-967
    CrossrefPubMedGoogle Scholar
  • 110 Russo MW, Kwok R, Serper M. et al. Impact of the Corona virus disease 2019 pandemic on hepatology practice and provider burnout. Hepatol Commun 2022; 6: 1236-1247
    CrossrefPubMedGoogle Scholar
  • 111 Milic J, Barbieri S, Gozzi L. et al. Metabolic-associated fatty liver disease is highly prevalent in the postacute COVID syndrome. Open Forum Infect Dis 2022; 9 ofac003
    PubMedGoogle Scholar
  • 112 Wang J, Hou Z, Liu J. et al. Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): a multicenter study. J Hepatol 2021; 75: 439-441
    CrossrefPubMedGoogle Scholar