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 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 3  |  Issue : 1  |  Page : 6-8

Liver injury among coronavirus disease patients


1 Assistant Professor, College of Nursing, Institute of Liver and Biliary Sciences, New Delhi, India
2 Department of Interventional Radiology, ILBS, New Delhi, India

Date of Submission02-Sep-2021
Date of Decision15-Dec-2021
Date of Acceptance19-Dec-2021
Date of Web Publication25-Feb-2022

Correspondence Address:
Jitender Singh
Department of Interventional Radiology, ILBS, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jssrp.jssrp_21_21

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  Abstract 


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as Coronavirus disease 2019 (COVID-19), is a novel coronavirus first identified in December 2019 and has a broad spectrum of clinical presentations. With the expansion of related research, it was found that in addition to respiratory symptoms, digestive involvements and liver injury were reported among COVID-19 patients. Abnormal liver function was observed in cases of COVID-19, manifesting mainly as isolated elevated serum transaminase and lactate dehydrogenase levels. The current review highlights the possible explanation for liver injury among COVID-19 patients.

Keywords: Abnormal liver function, coronavirus disease 2019, etiopathogenesis, liver injury, severe acute respiratory syndrome coronavirus 2, transaminitis


How to cite this article:
Sharma T, Singh J. Liver injury among coronavirus disease patients. J Surg Spec Rural Pract 2022;3:6-8

How to cite this URL:
Sharma T, Singh J. Liver injury among coronavirus disease patients. J Surg Spec Rural Pract [serial online] 2022 [cited 2022 May 22];3:6-8. Available from: https://jssrp.org/text.asp?2022/3/1/6/338533




  Introduction Top


Coronavirus disease 2019 (COVID-19) pandemic has aroused a global threat to human health. With the expansion of related research, it was found that in addition to respiratory symptoms, digestive involvements and liver injury were reported among COVID-19 patients.[1] The presence of abnormal liver enzymes in patients with COVID-19 was first reported by Chen et al., in their study among the 99 patients confirmed to have COVID-19, 43 had alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels above the normal range, 75 were reported to have elevated lactate dehydrogenase (LDH) levels, and one had severely impaired liver function, while the basic liver disease was not reported in these cases.[2] Recently, increasing evidence has highlighted the close relationship of abnormal liver biochemistries with the severity of COVID-19. In the cohort of 1099 patients with COVID-19 from mainland China, 39.4% had AST >40 U/L and 28.1% had ALT >40 U/L, and most of them occurred in severe and critical cases.[3] In other studies also, abnormal liver function was observed in cases of COVID-19, manifesting mainly as isolated elevated serum transaminase and LDH levels.[4],[5] There lies a multifactorial explanation [Figure 1] for the onset of liver injury among COVID-19 patients such as direct effect of virus on the liver, stress-induced liver injury, sepsis-induced liver injury, ischemic/hypoxic liver injury, drug-induced liver injury or the presence of preexisting liver disease and has been highlighted in the current review [Figure 2].
Figure 1: Multiple factors leading to liver injury in coronavirus disease patients

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Figure 2: Etiopathogenesis of liver injury among coronavirus disease patients

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  Direct Effect of Virus on the Liver (Viral Immunogenic Injury) Top


Liver damage in COVID-19 patients may be caused by the virus directly affecting liver cells. Studies[6],[7],[8] have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the ACE2 receptor, enabling the virus to replicate in cells. In addition, the expression level of ACE2 is very low in liver cells, accounting for 2.6% of the total number of cells, but highly specific in cholangiocytes, the bile duct cells (59.7%), which is similar to the expression level in major targeted cells (type II alveolar cells) of SARS-CoV-2 in the lung.[9],[10] Therefore, the novel coronavirus does not necessarily directly infect liver cells, but causes bile duct dysfunction by binding with cholangiocytes (bile duct cells), which play an important role in liver regeneration and immune response. Liver injury may be induced by damage to cholangiocytes caused by COVID-19.[11]


  Stress Induced Liver Injury Top


Hyperactivated immune responses and cytokine storm-related systemic inflammation in SARS-CoV-2 infection can affect and damage many organs, including the gut and liver. Stress-induced liver injury might be associated with hypoxia-reoxygenation, over-activation of Kupffer cells and oxidative stress, intestinal endotoxemia, and activation of the sympathetic nervous and adrenocortical system in COVID-19 patients leading to increased peripheral blood levels of CD8 T cells, interleukin-2, interleukin-6, interleukin-7, interleukin-10, tumor necrosis factor-α, granulocyte-colony stimulating factor, interferon-inducible protein-10, monocyte chemotactic protein 1 etc., among COVID patients with severe disease.[12],[13]


  Sepsis Induced Liver Injury Top


Sepsis in COVID-19 patients might be one of the etiologies of liver injury and substantially impairs the prognosis of COVID-19. The pathophysiology of sepsis-related liver injury includes hypoxic liver injury due to ischemia and shock, cholestasis due to altered bile metabolism, hepatocellular injury due to drug toxicity or overwhelming inflammation.[14]


  Ischemic/Hypoxic Liver Injury Top


Patients with COVID-19 are at risk of having hypoxia and shock. Severe hypoxia and hypovolemia are the major cause of ischemic/hypoxic liver injury in COVID-19 cases with acute lung failure and/or shock. Ischemic/hypoxic liver injury is associated with metabolic acidosis, calcium overloading, and changes of mitochondrial membrane permeability, and has thus far usually manifested as very high aminotransferase concentrations in serum.[15]


  Drug Induced Liver Injury Top


Many drugs which are used for the treatment of COVID-19 such as antipyretics (e.g., paracetamol) or antivirals (e.g., oseltamivir, lopinavir, and ritonavir) may be hepatotoxic in nature. Simultaneous use of these drugs may be the reason for drug-induced liver injury. If an abnormality of liver enzymes occurs after using a hepatotoxic drug, drug-induced liver injury should first be confirmed or ruled out.[16] In addition, large number of population may also use complementary and alternative medicine (therapy) to prevent infection, which may also induce liver injury. Patients with chronic liver disease, such as those with hepatitis B or hepatitis C, which may have preexisting elevated transaminase levels before treatment, could pose an increased risk of drug-induced liver injury.[1]


  Preexisting Liver Disease Top


According to the current reports, 1.25%–11% of patients with COVID-19 had preexisting liver diseases. Nonalcoholic fatty liver disease is the common cause of liver function abnormalities in the general population and could also be the cause of liver injuries in COVID-19. Metabolic factors such as obesity and diabetes are highly prevalent in critical cases and associated with mortality in COVID-19.[4] For patients under antiviral therapy, discontinuation of drugs during COVID-19 or the administration of glucocorticoids may also induce the activation of hepatitis B and induce hepatic injuries. For patients with cirrhosis, the systemic inflammation, hypoxia, and circulatory disturbances driven by COVID-19 could induce secondary infection or hepatic decompensation, leading to the exacerbation of preexisting liver disease.[1]


  Conclusion Top


Liver injury has been seen commonly in COVID-19 patients. The underlying mechanism of liver injury in patients with COVID-19 could be due to the direct effect of virus on the liver, stress-induced liver injury, sepsis-induced liver injury, ischemic/hypoxic liver injury, drug-induced liver injury, or the presence of preexisting liver disease. Hence, frequent and careful monitoring of liver function in patients with COVID-19 is very important which can lead to early diagnosis of hepatitis, liver injury, and liver failure among these patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Yang RX, Zheng RD, Fan JG. Etiology and management of liver injury in patients with COVID-19. World J Gastroenterol 2020;26:4753-62.  Back to cited text no. 1
    
2.
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. 2
    
3.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.  Back to cited text no. 3
    
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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. 4
    
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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. 5
    
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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. 6
    
7.
Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV Infection. bioRxiv; 2020. DOI: 10.1101/2020.02.03.931766.  Back to cited text no. 7
    
8.
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;181:271-280.e8. doi: 10.1016/j.cell.2020.02.052.  Back to cited text no. 8
    
9.
Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-Cell RNA Expression Profiling of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020 Sep 1;202(5):756-759. doi: 10.1164/rccm.202001-0179LE. Erratum in: Am J Respir Crit Care Med. 2021;203:782. PMID: 32663409; PMCID: PMC7462411.  Back to cited text no. 9
    
10.
Zhang H, Kang Z, Gong H, Xu D, Wang J, Li Z, et al. Digestive system is a potential route of COVID-19: An analysis of single-cell coexpression pattern of key proteins in viral entry processGut 2020;69:1010-8.  Back to cited text no. 10
    
11.
Wu J, Song S, Cao HC, Li LJ. Liver diseases in COVID-19: Etiology, treatment and prognosis. World J Gastroenterol 2020;26:2286-93.  Back to cited text no. 11
    
12.
Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L, et al. Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia. J Infect Dis 2020;221:1762-9. doi: 10.1093/infdis/jiaa150. PMID: 32227123; PMCID: PMC7184346.  Back to cited text no. 12
    
13.
Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020;11:827. doi: 10.3389/fimmu.2020.00827. PMID: 32425950; PMCID: PMC7205903.  Back to cited text no. 13
    
14.
Strnad P, Tacke F, Koch A, Trautwein C. Liver – Guardian, modifier and target of sepsis. Nat Rev Gastroenterol Hepatol 2017;14:55-66.  Back to cited text no. 14
    
15.
Li J, Li RJ, Lv GY, Liu HQ. The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. Eur Rev Med Pharmacol Sci 2015;19:2036-47.  Back to cited text no. 15
    
16.
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. 16
    


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Abstract
Introduction
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