• Users Online: 70
  • Print this page
  • Email this page


 
 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 42-44

Mechanism and computed tomography features of liver injury caused by coronavirus disease 2019: Current status


1 Department of Radiology, Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China
2 Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, China

Date of Submission08-Mar-2021
Date of Acceptance13-Sep-2021
Date of Web Publication18-Nov-2021

Correspondence Address:
Prof. Hongjun Li
Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing
China
Prof. Tianwu Chen
Department of Radiology, Sichuan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/RID.RID_5_21

Rights and Permissions
  Abstract 


Liver injury is found in some patients with coronavirus disease-2019 (COVID-19). Both the clinical treatment efficacy and the patient's prognosis are affected by the severity of liver injury. In addition, in some cases, liver injury may occur in the absence of respiratory symptoms. To date, liver injury diagnosed based on laboratory findings and abdominal computed tomography (CT) has been reported in COVID-19 patients. The aim of this review was to summarize the mechanism of liver injury caused by COVID-19 and describe the CT features of COVID-19-induced liver damage.

Keywords: Coronavirus disease; liver injury; angiotensin-converting enzyme; tomography, X-ray computed


How to cite this article:
Lu F, Ou J, Li R, Tan B, Zhang X, Chen T, Li H. Mechanism and computed tomography features of liver injury caused by coronavirus disease 2019: Current status. Radiol Infect Dis 2021;8:42-4

How to cite this URL:
Lu F, Ou J, Li R, Tan B, Zhang X, Chen T, Li H. Mechanism and computed tomography features of liver injury caused by coronavirus disease 2019: Current status. Radiol Infect Dis [serial online] 2021 [cited 2021 Dec 8];8:42-4. Available from: http://www.ridiseases.org/text.asp?2021/8/1/42/330566




  Introduction Top


The coronavirus disease-2019 (COVID-19) is a significant public health challenge worldwide. The lung is considered the primary organ targeted by COVID-19 infection.[1] In addition, the occurrence of liver injury has been reported during the course of this disease, and cases of severe acute liver injury have been shown to be associated with increased mortality.[2] In this review, we summarized the mechanism underlying liver injury caused by COVID-19 and the correlation of liver injury severity with computed tomography (CT) presentations using the available evidence reported to date.


  Mechanism of Liver Damage Caused by Coronavirus Disease 2019 Top


During the natural progression of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, liver injury is commonly observed in COVID-19 patients.[3] The injury might be caused by a viral infection of liver cells, adverse drug reactions, systemic inflammation, underlying liver diseases, hypoxic hepatitis, or other factors.[4] According to recent research, angiotensin-converting enzyme 2 (ACE-2) expression in the host is crucial for viral entry.[5],[6] As reported in the research by Hamming et al.,[7] the COVID-19 virus infects the endothelial cells of the liver through intestinal translocation or by binding to ACE-2 receptors. ACE-2 receptors are expressed in bile duct epithelial cells and appear to determine the susceptibility to the COVID-19 virus, similar to SARS-Cov.[8] The liver becomes a potential target for COVID-19. Moreover, COVID-19 may cause deterioration of underlying chronic liver diseases, leading to hepatic decompensation, chronic liver failure, poor outcomes, or even death. High expression of ACE-2 is detected in cholangiocytes, which dedifferentiate and proliferate to become new liver cells. These new liver cells have increased expression of active ACE-2, which increases the infectivity and damage of the liver.[9]

In the research by Zhu et al.,[10] 65% of patients with COVID-19 had unusual liver profiles with values over the upper limit of normal for alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT). Patients with COVID-19 primarily present with typical respiratory symptoms. At first, ALT and AST increase because of acute lung infections. The systemic inflammatory infection leads to an increase in these biochemical indicators. As the disease rapidly progresses, several factors influence AST and ALT levels. According to recent studies,[11],[12] the risk of liver injury is increased with severe disease, advanced age, and underlying comorbidities, such as diabetes, hypertension, renal failure, and heart disease. Importantly, patients with metabolic-associated fatty liver disease are more likely to show an increased risk of severe illness. Obesity is also associated with a higher risk of infection by the COVID-19 virus.[13]

In studies on existing COVID-19 cases,[14],[15] GGT was not frequently reported as a cholestatic marker. GGT was demonstrated to be elevated in approximately half of all COVID-19 patients during the hospitalization period. The hepatotoxicity of drugs is a problem that cannot be ignored.[16] By controlling statistical models for azithromycin or lopinavir/ritonavir intake, researchers found that drug-induced liver injury did not play a major role in the described pattern of liver injury.[8] ALT and AST elevation at admission might be a consequence of respiratory impairment during the early stages and should not be associated with poor prognosis, whereas out-regulated GGT and ALP trajectories during hospitalization were shown to be associated with liver injury and decreased survival.[17-28]

The mechanism of liver injury in patients with COVID-19 remains poorly understood. GGT and ALP provide useful biomarkers for stratifying a population by risk and identifying patients requiring additional surveillance and intensive care. They may also be indicators for evaluating the treatment effect and prognosis of COVID-19 patients.


  Computed Tomography Features of Liver Damage Caused by Coronavirus Disease 2019 Top


Patients with COVID-19 commonly show ground-glass opacities, smooth or irregular interlobular septal thickening, consolidation with air bronchogram, and pleural effusion in the lungs on chest CT.[29] The radiologic manifestations of the liver change in the presence of liver damage induced by SARS-Cov-2. In the study by Lei et al.,[30] they reported a correlation of liver injury radiologic features with different clinical severities, suggesting that the semiquantitative scoring of pulmonary lesions is associated with severity grading and liver function tests. However, the pulmonary semiquantitative assessment has limitations. For example, it can be influenced by subjective factors when the occurrence of liver damage and liver function is assessed. Among patients infected with SARS-Cov-2, homogeneous or heterogeneous hepatic hypodensity was the most common CT finding. Liver hypodensity was observed in 26.09% of patients, and statistical analysis showed significant differences between groups with different severities of liver injury.[31]

By measuring hepatic and splenic attenuation values in Hounsfield unit on CT images obtained at admission, the liver-to-spleen attenuation (L/S) was also investigated and identified as a significant variable for dividing different severity groups of COVID-19.[30] Uchida et al.[31] reported an optimal cut-off value of the L/S ratio (1.03) to identify patients with different severities of COVID-19. However, studies by Byun et al.[32] showed that the cut-off values vary with the tube voltage. Specifically, the L/S cut-off value defined at 120 kV did not apply to 100 kV. In summary, the hepatic CT attenuation values and L/S ratios were lower in patients with severe COVID-19 than in those with mild-to-moderate disease. By measuring the L/S, radiologists can make a preliminary estimate of liver injury in patients with COVID-19. The L/S ratio provides a potential marker to predict adverse liver damage outcomes in patients with COVID-19.[31]


  Conclusion Top


The available results support the assumption that liver damage may be associated with severe outcomes in patients with COVID-19. At present, the assessment of liver injury severity mainly relies on laboratory and radiologic examinations. On the one hand, the severity of liver injury is significantly related to AST and ALT levels. On the other hand, the L/S ratio is an accurate indicator to determine the severity of liver injury in patients with COVID-19. Both laboratory and radiologic results may help identify patients with liver injury for proper treatment decision-making.

Acknowledgments

We thank Melissa Crawford, Ph.D., from Liwen Bianji (Edanz) (www.liwenbianji.cn/), for editing the English text of a draft of this manuscript.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was supported by the Nanchong City Level Science and Technology Plan Project for the Novel Coronavirus Epidemic Prevention and Control Category (Grant No. 20YFZJ0103), the Key Project of National Natural Science Foundation of China (Grant No. 61936013), and the National Natural Science Foundation of China (Grant No. 81801674) for the conduct of this study.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Zu ZY, Jiang MD, Xu PP, Chen W, Ni QQ, Lu GM, et al. Coronavirus disease 2019 (COVID-19): A perspective from China. Radiology 2020;296:E15-25.  Back to cited text no. 1
    
2.
Lei F, Liu YM, Zhou F, Qin JJ, Zhang P, Zhu L, et al. Longitudinal association between markers of liver injury and mortality in COVID-19 in China. Hepatology 2020;72:389-98.  Back to cited text no. 2
    
3.
Xu L, Liu J, Lu M, Yang D, Zheng X. Liver injury during highly pathogenic human coronavirus infections. Liver Int 2020;40:998-1004.  Back to cited text no. 3
    
4.
Fix OK, Hameed B, Fontana RJ, Kwok RM, McGuire BM, Mulligan DC, et al. Clinical best practice advice for hepatology and liver transplant providers during the COVID-19 pandemic: AASLD expert panel consensus statement. Hepatology 2020;72:287-304.  Back to cited text no. 4
    
5.
Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020;367:1444-8.  Back to cited text no. 5
    
6.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.e8.  Back to cited text no. 6
    
7.
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004;203:631-7.  Back to cited text no. 7
    
8.
Bernal-Monterde V, Casas-Deza D, Letona-Giménez L, de la Llama-Celis N, Calmarza P, Sierra-Gabarda O, et al. SARS-CoV-2 infection induces a dual response in liver function tests: Association with mortality during hospitalization. Biomedicines 2020;8:E328.  Back to cited text no. 8
    
9.
Guan GW, Gao L, Wang JW, Wen XJ, Mao TH, Peng SW, et al. Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia. Zhonghua Gan Zang Bing Za Zhi 2020;28:100-6.  Back to cited text no. 9
    
10.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. China novel coronavirus investigating and research team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382:727-33.  Back to cited text no. 10
    
11.
Hussain A, Vasas P, El-Hasani S. Letter to the editor: Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease. Metabolism 2020;108:154256.  Back to cited text no. 11
    
12.
Yang K, Sheng Y, Huang C, Jin Y, Xiong N, Jiang K, et al. Clinical characteristics, outcomes, and risk factors for mortality in patients with cancer and COVID-19 in Hubei, China: A multicentre, retrospective, cohort study. Lancet Oncol 2020;21:904-13.  Back to cited text no. 12
    
13.
Muscogiuri G, Pugliese G, Barrea L, Savastano S, Colao A. Commentary: Obesity: The “Achilles heel” for COVID-19? Metabolism 2020;108:154251.  Back to cited text no. 13
    
14.
Cai Q, Huang D, Yu H, Zhu Z, Xia Z, Su Y, et al. COVID-19: Abnormal liver function tests. J Hepatol 2020;73:566-74.  Back to cited text no. 14
    
15.
Zhang C, Shi L, Wang FS. Liver injury in COVID-19: Management and challenges. Lancet Gastroenterol Hepatol 2020;5:428-30.  Back to cited text no. 15
    
16.
Fan Z, Chen L, Li J, Cheng X, Yang J, Tian C, et al. Clinical features of COVID-19-related liver functional abnormality. Clin Gastroenterol Hepatol 2020;18:1561-6.  Back to cited text no. 16
    
17.
Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. China medical treatment expert group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.  Back to cited text no. 17
    
18.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.  Back to cited text no. 18
    
19.
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.  Back to cited text no. 19
    
20.
Wu J, Liu J, Zhao X, Liu C, Wang W, Wang D, et al. Clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu province: A multicenter descriptive study. Clin Infect Dis 2020;71:706-12.  Back to cited text no. 20
    
21.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.  Back to cited text no. 21
    
22.
Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ 2020;368:m1091.  Back to cited text no. 22
    
23.
Pan F, Ye T, Sun P, Gui S, Liang B, Li L, et al. Time course of lung changes at chest CT during recovery from coronavirus disease 2019 (COVID-19). Radiology 2020;295:715-21.  Back to cited text no. 23
    
24.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020;180:934-43.  Back to cited text no. 24
    
25.
Zhang Y, Zheng L, Liu L, Zhao M, Xiao J, Zhao Q. Liver impairment in COVID-19 patients: A retrospective analysis of 115 cases from a single centre in Wuhan city, China. Liver Int 2020;40:2095-103.  Back to cited text no. 25
    
26.
Xie H, Zhao J, Lian N, Lin S, Xie Q, Zhuo H. Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: A retrospective study. Liver Int 2020;40:1321-6.  Back to cited text no. 26
    
27.
Xu X, Wu X, Jiang X, Xu K, Ying L, Ma C, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series. BMJ 2020;368:m606.  Back to cited text no. 27
    
28.
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020;8:475-81.  Back to cited text no. 28
    
29.
Li B, Li X, Wang Y, Han Y, Wang Y, Wang C, et al. Diagnostic value and key features of computed tomography in coronavirus disease 2019. Emerg Microbes Infect 2020;9:787-93.  Back to cited text no. 29
    
30.
Lei P, Zhang L, Han P, Zheng C, Tong Q, Shang H, et al. Liver injury in patients with COVID-19: Clinical profiles, CT findings, the correlation of the severity with liver injury. Hepatol Int 2020;4:1-10.  Back to cited text no. 30
    
31.
Uchida Y, Uemura H, Yamaba S, Hamada D, Tarumoto N, Maesaki S, et al. Significance of liver dysfunction associated with decreased hepatic CT attenuation values in Japanese patients with severe COVID-19. J Gastroenterol 2020;9:1-9.  Back to cited text no. 31
    
32.
Byun J, Lee SS, Sung YS, Shin Y, Yun J, Kim HS, et al. CT indices for the diagnosis of hepatic steatosis using non-enhanced CT images: Development and validation of diagnostic cut-off values in a large cohort with pathological reference standard. Eur Radiol 2019;29:4427-35.  Back to cited text no. 32
    




 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Mechanism of Liv...
Computed Tomogra...
Conclusion
References

 Article Access Statistics
    Viewed220    
    Printed8    
    Emailed0    
    PDF Downloaded28    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]