Characteristics of the liver parenchyma according to the native CT examinations data at the stages of COVID-19 treatment

Purpose. To assess the liver density according to the data of native CT studies in patients with COVID-19, depending on the severity of the pulmonary parenchyma damage and the prescribed treatment, to compare the data with biochemical indicators, and also to demonstrate changes in density indicators over time.

Material and methods. Lung CT data from 200 patients with COVID-19 were retrospectively analyzed. The density of the liver, spleen, and subcutaneous fat tissue was measured in all patients on the images of the upper abdominal cavity that entered the scan area. The ratio of the density of the liver to the spleen and to the density of the fat tissue was assesed. These indicators were compared with each other in two groups of lung tissue damage: CT 1—2 and CT 3—4. The CT 3—4 group was assessed in detail: the density indicators of the liver were studied in dynamics, and their relationship with biochemical indicators — during the initial study. A comparison was also made between two subgroups: patients taking tocilizumab and those without tocilizumab.

Results. A decrease in liver density and the ratio of liver density to spleen density was observed in 35.5% and 47.5% of patients respectively. Liver density and the ratio of liver density to spleen density were lower in the CT 3—4 group than in the CT 1—2 group, and amounted to 43.9 HU versus 49.3 HU (p < 0.008) and 0.9 versus 1.0 respectively (p < 0.014). In the initial study, there were a moderate (r = -0.30; p < 0.05) and weak (r = -0.26; p < 0.05) negative correlation of liver density and the ratio of liver density to spleen density with serum albumin. When assessing the dynamics in patients in the CT 3—4 group, with each subsequent study, an increase in the density of the liver parenchyma and the ratio of liver density to spleen density was noted. The difference between the mean values of liver density at the first and at the fourth CT examinations was 11.85 HU. Liver density values were independent of treatment with tocilizumab.

Conclusion. Liver density values were lower in patients with COVID-19 with the degree of lung parenchyma lesion CT 3—4, increased during treatment and did not depend on the prescription of tocilizumab. Evaluation and monitoring of the dynamics of liver density could become a useful parameter in determining the severity of the disease course. No strong relationships were found between the density parameters during primary CT and any of the biochemical parameters. A more detailed analysis of these changes in dynamics is required, which may suggest the prevailing mechanism of liver damage in COVID-19.

1. Gorbalenya A.E., Baker S.C., Baric R.S., de Groot R.J., Drosten C., Gulyaeva A.A., Haagmans B.L., Lauber C., Leontovich A.M., Neuman B.W., Penzar D., Perlman S., Poon L.L.M., Samborskiy D.V., Sidorov I.A., Sola I., Ziebuhr J. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020; 5 (4): 536-544. https://doi.org/10.1038/s41564-020-0695-z.

2. Coronavirus disease (COVID-19) Situation dashboard. World Health Organization, 24 May 2020. https://covid19.who.int.

3. Zhai P., Ding Y., Wu X., Long J., Zhong Y., Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int. J. Antimicrob. Agents. 2020; 55 (5): 105955. https://doi.org/10.1016/j.ijantimicag.2020.105955.

4. Feng G., Zheng K.I., Yan Q.Q., Rios R.S., Targher G., Byrne C.D., Poucke S.V., Liu W.Y., Zheng M.H. COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies. J. Clin. Translat. Hepatol. 2020: 8 (1): 18-24. https://doi.org/10.14218/JCTH.2020.00018.

5. Luchevaya diagnostika koronavirusnoj bolezni (COVID-19): organizaciya, metodologiya, interpretaciya rezul'tatov [Radiology diagnosis of coronavirus disease (COVID-19): organization, methodology, interpretation of results]. Preprint No. CDT -2020 - II Version 2 (17.04.2020). Text: electronic. (In Russian)

6. Fang Y., Zhang H., Xie J., Lin M., Ying L., Pang P., Ji W. Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR. Radiology. 2020; 296 (2): E115-E117. https://doi.org/10.1148/radiol.2020200432.

7. Xie X., Zhong Z., Zhao W., Zheng C., Wang F., Liu J. Chest CT for typical 2019-nCoV pneumonia: relationship to negative RT-PCR testing. Radiology. 2020; 296 (2): E41-E45. https://doi.org/10.1148/radiol.2020200343.

8. Morozov S.P., Procenko D.N., Smetanina S.V., Andrej-chenko A.E., Ambrosi O.E., Balanjuk Je.A., Vladzimirskij A.V., Vetsheva N.N., Gombolevskij V.A., Epifanova S.V., Ledihova N.V., Lobanov M.N., Pavlov N.A., Panina E.V., Polishhuk N.S., Ridjen T.V., Sokolina I.A., Turavilova E.V., Fedorov S.S., Chernina V.Ju., Shul'kin I.M. Luchevaya diagnostika koronavirusnoj bolezni (COVID-19): organizaciya, metodologiya, interpretaciya rezul'tatov [RadiologicalI maging of COVID19: organization, methodology and interpretation]. Moscow: The Department of Health of Moscow, 2020. 81 p. (In Russian)

9. Karmazanovsky G.G., Zamyatina K.A., Stashkiv V.I., Shantarevich M.Yu., Kondratyev E.V., Semenov F.M., Kuznetsova S.Yu., Kozlova A.V., Plotnikov G.P., Popov V.A., Chupin A.V., Gritskevich A.A., Chililov A.M., Pechetov A.A., Kurochkina A.I., Khokhlov V.A., Kalinin D.V. CT diagnostics and monitoring of the course of viral pneumonia caused by the SARS-CoV-2 virus during the work of the “COVID-19 Hospital”, based on the Federal Specialized Medical Scientific Center. Medical Visualization. 2020; 24 (2): 11-36. https://doi.org/10.24835/1607-0763-2020-2-11-36 (In Russian)

10. Informaciya o novoj koronavirusnoj infekcii dlya medicinskih rabotnikov [Recommendations for doctors on Covid-19 of the Ministry of Health of the Russian Federation]. 2020. https://www.rosminzdrav.ru/ministry/med_covid19. (In Russian)

11. Assessment Report ForRoActemra [Internet] 1st ed. London: European Medicines Agency; 2009. [accessed 2017 January3]. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR__Public_assessment_report/human/000955/WC500054888.pdf.

12. Vremennye metodicheskie rekomendacii. Profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19) [Temporary guidelines. Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)]. 2020; Version 6. https://www.rosminzdrav.ru/ministry/med_covid19 (In Russian)

13. Lei P., Zhang L., Han P., Zheng Ch., Tong Q., Shang H., Yang F., Hu Yu., Li X., Son Yu. Liver injury in patients with COVID-19: clinical profiles, CT findings and their correlation with the severity. Eur. J. Pediatr. 2020; 18: 1-18. https://doi.org/10.21203/rs.3.rs-28692/v1.

14. Xu L., Liu J., Lu M., Yang D., Zheng X. Liver injury during highly pathogenic human coronavirus infections. Liver Int. 2020; 40 (5): 998-1004. https://doi.org/10.1111/liv.14435.

15. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., Xia Jia'an, Yu T., Zhang X., Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395 (10223): 507-513. https://doi.org/10.1016/S0140-6736(20)30211-7.

16. Zhang C., Shi L., Wang F.S. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol. Hepatol. 2020; 5 (5): 428-430. https://doi.org/10.1016/S2468-1253(20)30057-1.

17. Guan W., Ni Z., Hu Yu, Liang W., Ou C., He J., Liu L., Shan H., Lei C., Hui D.S.C., Du B., Li L., Zeng G., Yuen K.-Y., Chen R., Tang C., Wang T., Chen P., Xiang J., Li S., Wang Jin-lin, Liang Z., Peng Y., Wei L., Liu Y., Hu Ya-hua, Peng P., Wang Jian-ming, Liu J., Chen Z., Li G., Zheng Z., Qiu S., Luo J., Ye C., Zhu S., Zhong N. Clinical characteristics of 2019 novel coronavirus infection in China. N. Engl. J. Med. 2020; 382 (18): 1708-1720. https://doi.org/10.1056/NEJMoa2002032.

18. Ji D., Qin E., Xu J., Zhang D., Cheng G., Wang Y., Lau G. Implication of non-alcoholic fatty liver diseases (NAFLD) in patients with COVID-19: a preliminary analysis. J. Hepatol. 2020; 73 (2): 451-453. https://doi.org/10.1016/j.jhep.2020.03.044.

19. Shi H., Han X., Jiang N., Cao Y., Alwalid O., Gu J., Zheng C. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect. Dis. 2020; 20 (4): 425-434. http://dx.doi.org/10.1016/S1473-3099(20)30086-4.

20. Kumar P., Sharma M., Kulkarni A., Rao P.N. Pathogenesis of liver injury in coronavirus disease 2019. J. Clin. Exp. Hepatol. 2020; May 20. (in press, corrected proof available online [accessed: 2020 June 01]) https://www.jcehepatology.com/article/S0973-6883(20)30074-8/abstract. https://doi.org/10.1016/j.jceh.2020.05.006.

21. 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. Preprint February 04, 2020. https://doi.org/10.1101/2020.02.03.931766.

22. Hanley B., Lucas S.B., Youd E., Swift B., Osborn M. Autopsy in suspected COVID-19 cases. J. Clin. Pathol. 2020; 73 (5): 239242. https://doi.org/10.1136/jclinpath-2020-206522.

23. Hodgman M.J., Garrard A.R. A review of acetaminophen poisoning. Crit. Care Clin. 2012; 28 (4): 499-516. https://doi.org/10.1016/j.ccc.2012.07.006.

24. Fan Z., Chen L., Li J., Cheng X., Yang J., Tian C., Zhang Y., Huang S., Liu Z., Cheng J. Clinical features of COVID-19-related liver damage. Clin. Gastroenterol. Hepatol. 2020; 18 (7): 1561-1566. https://doi.org/10.1016/j.cgh.2020.04.002.

25. Zhang X.J., Cheng X., Yan Z.Z., Fang J., Wang X., Wang W.., Liu Z.-Y., Shen L.-J., Zhang P. , Wang P.-X., Liao R., Ji Y.-X., Wang J.-Y., Tian S., Zhu X.-Y., Zhang Y., Tian R.-F., Wang L., Ma X.-L., Huang Z., She Z.-G., Li H.. An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemiareperfusion injury. Nat. Med. 2018; 24 (1): 73-83. https://doi.org/10.1038/nm.4451.