COVID-19: Abnormal liver function tests

Qingxian Cai, Deliang Huang, Hong Yu, Zhibin Zhu, Zhang Xia, Yinan Su, Zhiwei Li, Guangde Zhou, Jizhou Gou, Jiuxin Qu, Yan Sun, Yingxia Liu, Qing He, Jun Chen, Lei Liu, Lin Xu, Qingxian Cai, Deliang Huang, Hong Yu, Zhibin Zhu, Zhang Xia, Yinan Su, Zhiwei Li, Guangde Zhou, Jizhou Gou, Jiuxin Qu, Yan Sun, Yingxia Liu, Qing He, Jun Chen, Lei Liu, Lin Xu

Abstract

Background & aims: Recent data on the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun to shine light on the impact of the disease on the liver. But no studies to date have systematically described liver test abnormalities in patients with COVID-19. We evaluated the clinical characteristics of COVID-19 in patients with abnormal liver test results.

Methods: Clinical records and laboratory results were obtained from 417 patients with laboratory-confirmed COVID-19 who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020. Information on clinical features of patients with abnormal liver tests were collected for analysis.

Results: Of 417 patients with COVID-19, 318 (76.3%) had abnormal liver test results and 90 (21.5%) had liver injury during hospitalization. The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with 49 (23.4%), 31 (14.8%), 24 (11.5%) and 51 (24.4%) patients having alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase levels elevated to more than 3× the upper limit of normal, respectively. Patients with abnormal liver tests of hepatocellular type or mixed type at admission had higher odds of progressing to severe disease (odds ratios [ORs] 2.73; 95% CI 1.19-6.3, and 4.44, 95% CI 1.93-10.23, respectively). The use of lopinavir/ritonavir was also found to lead to increased odds of liver injury (OR from 4.44 to 5.03, both p <0.01).

Conclusion: Patients with abnormal liver tests were at higher risk of progressing to severe disease. The detrimental effects on liver injury mainly related to certain medications used during hospitalization, which should be monitored and evaluated frequently.

Lay summary: Data on liver tests in patients with COVID-19 are scarce. We observed a high prevalence of liver test abnormalities and liver injury in 417 patients with COVID-19 admitted to our referral center, and the prevalence increased substantially during hospitalization. The presence of abnormal liver tests and liver injury were associated with the progression to severe pneumonia. The detrimental effects on liver injury were related to certain medications used during hospitalization, which warrants frequent monitoring and evaluation for these patients.

Keywords: 2019-nCoV; Bilirubin; Critical care; Liver injury; Liver tests; Pneumonia; SARS-Cov-2.

Conflict of interest statement

Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Liver test abnormality during hospitalization in patients with COVID-19 by severity of disease. (Bars represent number of patients).
Fig. 2
Fig. 2
Adjusted odds ratios (95% CIs) for liver injury associated with use of drugs in patients with COVID-19. All results were adjusted for radiography image grade at admission, age, sex, body mass index and comorbidities. Triangle legends for results from multivariable regression and circle legends for inverse probability weighting. Levels of significance: both p values <0.01 for lopinavir/ritonavir; all p values >0.05 for other drugs (multivariable logistic regression). IPW, inverse probability weighting; NSAIDs, non-steroidal anti-inflammatory drugs.
Fig. 3
Fig. 3
Liver biopsy of 1 patient aged 69 years who died from the COVID-19. (A) (20×) There was no obvious inflammation in the portal area. The structure of interlobular bile duct, interlobular vein and interlobular artery was clear; the hepatocytes in the interlobular were arranged orderly, and a few hepatocytes were observed slightly vesicular steatosis and watery degeneration (possibly related to ischemia and hypoxia). (B) (40×) The hepatocytes were observed slightly vesicular steatosis and watery degeneration, and a few inflammatory cells (neutrophils, plasma cells and Kupffer cells) were found in hepatic sinuses.

References

    1. Dong Y., Liang X., Yu X. Prognostic value of the dynamic changes in extra vascular lung water index and angiopoietin-2 in severe multiple trauma patients with acute respiratory distress syndromeZhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019;31:571–576.
    1. Niu P., Shen J., Zhu N., Lu R., Tan W. Two-tube multiplex real-time reverse transcription PCR to detect six human coronaviruses. Virologica Sinica. 2016;31:85–88.
    1. Lu R., Zhao X., Li J., Niu P., Yang B., Wu H. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–574.
    1. Jia Z., Yan L., Ren Z., Wu L., Wang J., Guo J. Delicate structural coordination of the Severe Acute Respiratory Syndrome coronavirus Nsp13 upon ATP hydrolysis. Nucleic Acids Res. 2019;47:6538–6550.
    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 doi: 10.1001/jama.2020.2648. Published online February 24, 2020.
    1. Chau T.N., Lee K.C., Yao H., Tsang T.Y., Chow T.C., Yeung Y.C. SARS-associated viral hepatitis caused by a novel coronavirus: report of three cases. Hepatology. 2004;39:302–310.
    1. Chai X., Hu L., Zhang Y., Han W., Lu Z., Ke A. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv. 2020 doi: 10.1101/2020.02.03.931766.
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513.
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. Tian S., Hu N., Lou J., Chen K., Kang X., Xiang Z. Characteristics of COVID-19 infection in Beijing. J Infect. 2020;80:401–406.
    1. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020 doi: 10.1056/NEJMoa2002032. Published online February 28, 2020.
    1. Yang W., Cao Q., Qin L., Wang X., Cheng Z., Pan A. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): a multi-center study in Wenzhou city, Zhejiang, China. J Infect. 2020;80:388–393.
    1. Zhang J.J., Dong X., Cao Y.Y., Yuan Y.D., Yang Y.B., Yan Y.Q. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 doi: 10.1111/all.14238. Published online 19 February 2020.
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069.
    1. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 doi: 10.1016/S2213-2600(20)30076-X. Published online February 18, 2020.
    1. World Health Organization Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected: interim guidance. 2020. Available at.
    1. Bai Y., Yao L., Wei T., Tian F., Jin D.Y., Chen L. Presumed Asymptomatic Carrier transmission of COVID-19. JAMA. 2020 doi: 10.1001/jama.2020.2565. Published online February 21, 2020.
    1. Metlay J.P., Waterer G.W., Long A.C., Anzueto A., Brozek J., Crothers K. Diagnosis and treatment of Adults with community-acquired pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200:e45–e67.
    1. National Health Commission of the People's Republic of China Handbook of Prevention and Treatment of the Pneumonia Caused by the Novel Coronavirus (2019-nCoV) (in Chinese) 2020. Updated: February 6, 2020. Available at.
    1. European Association for the Study of the Liver, European Association for the Study of Diabetes EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Obes Facts. 2016;9:65–90.
    1. European Association for the Study of the Liver EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–398.
    1. Zhang C., Shi L., Wang F.S. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020 doi: 10.1016/S2468-1253(20)30057-1. Published online March 04, 2020.
    1. Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., Herrler T., Erichsen S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 doi: 10.1016/j.cell.2020.02.052. Published online March 05, 2020.
    1. 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;367:1444–1448.
    1. Clarke N.E., Turner A.J. Angiotensin-converting enzyme 2: the first decade. Int J Hypertens. 2012;2012:307315.
    1. Meraviglia P., Schiavini M., Castagna A., Viganò P., Bini T., Landonio S. Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation. HIV Med. 2004;5:334–343.
    1. Dillon J.F., Miller M.H. SAGE Publications Sage UK; London, England: 2016. Gamma glutamyl transferase ‘To be or not to be’a liver function test?
    1. Fernandez N.J., Kidney B.A. Alkaline phosphatase: beyond the liver. Vet Clin Pathol. 2007;36:223–233.
    1. Zhu Y., Niu M., Chen J., Zou Z-s, Ma Z-j, Liu S-h. Hepatobiliary and pancreatic: comparison between Chinese herbal medicine and Western medicine-induced liver injury of 1985 patients. J Gastroenterol Hepatol. 2016;31:1476–1482.
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020
    1. Xu X.W., Wu X.X., Jiang X.G., Xu K.J., Ying L.J., Ma C.L. 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.
    1. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727–733.
    1. MacLaren G., Fisher D., Brodie D. Preparing for the most critically ill patients with COVID-19: the potential role of extracorporeal membrane oxygenation. JAMA. 2020 doi: 10.1001/jama.2020.2342. Published online February 19, 2020.
    1. Zhang W. Imaging changes of severe COVID-19 pneumonia in advanced stage. Intensive Care Med. 2020:1–3.
    1. Andrade R.J., Aithal G.P., Bjornsson E.S., Kaplowitz N., Kullak-Ublick G.A., Karlsen T.H. EASL clinical practice guidelines: drug-induced liver injury. J Hepatol. 2019;70:1222–1261.

Source: PubMed

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