Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study)

Shiv Kumar Sarin, Ashok Choudhury, George K Lau, Ming-Hua Zheng, Dong Ji, Sherief Abd-Elsalam, Jaeseok Hwang, Xiaolong Qi, Ian Homer Cua, Jeong Ill Suh, Jun Gi Park, Opass Putcharoen, Apichat Kaewdech, Teerha Piratvisuth, Sombat Treeprasertsuk, Sooyoung Park, Salisa Wejnaruemarn, Diana A Payawal, Oidov Baatarkhuu, Sang Hoon Ahn, Chang Dong Yeo, Uzziel Romar Alonzo, Tserendorj Chinbayar, Imelda M Loho, Osamu Yokosuka, Wasim Jafri, Soeksiam Tan, Lau Ing Soo, Tawesak Tanwandee, Rino Gani, Lovkesh Anand, Eslam Saber Esmail, Mai Khalaf, Shahinul Alam, Chun-Yu Lin, Wan-Long Chuang, A S Soin, Hitendra K Garg, Kemal Kalista, Badamnachin Batsukh, Hery Djagat Purnomo, Vijay Pal Dara, Pravin Rathi, Mamun Al Mahtab, Akash Shukla, Manoj K Sharma, Masao Omata, APASL COVID Task Force, APASL COVID Liver Injury Spectrum Study (APCOLIS Study-NCT 04345640), Shiv Kumar Sarin, Ashok Choudhury, George K Lau, Ming-Hua Zheng, Dong Ji, Sherief Abd-Elsalam, Jaeseok Hwang, Xiaolong Qi, Ian Homer Cua, Jeong Ill Suh, Jun Gi Park, Opass Putcharoen, Apichat Kaewdech, Teerha Piratvisuth, Sombat Treeprasertsuk, Sooyoung Park, Salisa Wejnaruemarn, Diana A Payawal, Oidov Baatarkhuu, Sang Hoon Ahn, Chang Dong Yeo, Uzziel Romar Alonzo, Tserendorj Chinbayar, Imelda M Loho, Osamu Yokosuka, Wasim Jafri, Soeksiam Tan, Lau Ing Soo, Tawesak Tanwandee, Rino Gani, Lovkesh Anand, Eslam Saber Esmail, Mai Khalaf, Shahinul Alam, Chun-Yu Lin, Wan-Long Chuang, A S Soin, Hitendra K Garg, Kemal Kalista, Badamnachin Batsukh, Hery Djagat Purnomo, Vijay Pal Dara, Pravin Rathi, Mamun Al Mahtab, Akash Shukla, Manoj K Sharma, Masao Omata, APASL COVID Task Force, APASL COVID Liver Injury Spectrum Study (APCOLIS Study-NCT 04345640)

Abstract

Background and aims: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis.

Methods: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19.

Results: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients.

Conclusions: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Keywords: Acute liver injury; COVID-19; Chronic liver disease; SARS CoV2.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flow diagram. Enrolment of patients and acute liver injury. Acute liver injury was seen at presentation in 20% of CLD without cirrhosis, 16% of compensated and 55.6% of decompensated cirrhosis. Further acute liver injury was noted in 32.4% of those without cirrhosis and in 48% of compensated cirrhosis. Where as among the decompensated cirrhotics 27% had new onset acute liver injury
Fig. 2
Fig. 2
COVID-19 and Spectrum of CLD. a The incidence of severe disease due to COVID-19 increases progressively among non-cirrhotics to compensated to decompensated cirrhosis (p = 0.03) as the synthetic function decreased. b There is similar trend for acute liver injury (p = 0.02). c The mortality increased with SARS CoV2 infection significantly among cirrhotics than those without cirrhosis (p < 0.001) and with decompensation. The mortality is highest (43%) in the spectrum with onset of liver injury. d Among cirrhosis those exposed to SARS CoV2 infection, the outcome is poor with CTP score 9 or more [AUROC 0.94, sensitivity 86% and specificity of 94%, HR = 19.2 (95 CI 2.3–163.3), p < 0.001]

References

    1. Coronavirus disease (COVID-19) Situation Report – 113. Data as received by WHO from national authorities. 2020. .
    1. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574. doi: 10.1016/S0140-6736(20)30251-8.
    1. 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 doi: 10.1056/NEJMoa2002032.
    1. 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 doi: 10.1016/s2213-2600(20)30079-5.
    1. Chen C, Zhang XR, Ju ZY, He WF. Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies. Zhonghua Shaoshang Zazhi. 2020;36:E005.
    1. Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol. 2020 doi: 10.1002/jmv.25726.
    1. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020 doi: 10.1038/s41368-020-0074-x.
    1. Xie H, Zhao J, Lian N, et al. Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: a retrospective study. Liver Int. 2020 (online ahead of print)
    1. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020 doi: 10.1016/S2468-1253(20)30057-1.
    1. Fan Z, Chen L, Li J, et al. Clinical features of COVID-19-related liver damage. medRxiv. 10.1101/2020.02.26.20026971
    1. Li J, Jian-Gao F. Characteristics and mechanism of liver injury in 2019 coronavirus disease. J Clin Transl Hepatol. 2020 doi: 10.14218/JCTH.2020.00019.
    1. Feng G, Zheng KI, Yan Q-Q, et al. COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies. J Clin Transl Hepatol. 2020;8(1):18–24. doi: 10.14218/JCTH.2020.00018.
    1. Tian S, Xiong Y, Liu H, et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod Pathol. 2020 doi: 10.1038/s41379-020-0536-x.
    1. D'Antiga L. Coronaviruses and immunosuppressed patients. The facts during the third epidemic. Liver Transpl. 2020 (online ahead of print)
    1. Sarin SK. Fast, faster, and fastest: science on the run during COVID-19 drama—do not forget the liver. Hepatol Int. 2020 doi: 10.1007/s12072-020-10042-0.
    1. Eslam M, Sanyal AJ, George J, on behalf of the International Consensus Panel et al. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158(7):1999–2014.e1. doi: 10.1053/j.gastro.2019.11.312.
    1. Yang AP, Liu J, Tao W, Li HM. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharmacol. 2020 doi: 10.1016/j.intimp.2020.106504.
    1. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61(6):1385–1396. doi: 10.1016/j.jhep.2014.08.010.
    1. Sarin SK, Choudhury A. Acute-on-chronic liver failure. Curr Gastroenterol Rep. 2016;18(12):61. doi: 10.1007/s11894-016-0535-8.
    1. Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. WHO Interim guidance. COVID-19: Laboratory and diagnosis. 2020. .
    1. Clinical management of COVID-19. WHO interim guidance. COVID-19: Clinical care. 2020. .
    1. Stefan N, Birkenfeld AL, Schulze MB, et al. Obesity and impaired metabolic health in patients with COVID-19. Nat Rev Endocrinol. 2020 doi: 10.1038/s41574-020-0364-6.
    1. 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 Clin Res Rev. 2020;14:535–545. doi: 10.1016/j.dsx.2020.04.044.
    1. 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 doi: 10.1016/j.jhep.2020.03.044.
    1. Zhang Y, Zheng L, Liu L, et al. Liver impairment in COVID-19 patients: a retrospective analysis of 115 cases from a single center in Wuhan City, China. Liver Int. 2020 (online ahead of print)
    1. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘cytokine storm’ in COVID-19. J Infect. 2020 doi: 10.1016/j.jinf.2020.03.037.
    1. Cai Q, Huang D, Yu H, et al. COVID-19: abnormal liver function tests. J Hepatol. 2020 doi: 10.1016/j.jhep.2020.04.006.
    1. Lei F, Liu YM, Zhou F, Qin JJ, Zhang P. Longitudinal association between markers of liver injury and mortality in COVID-19 in China. Hepatology. 2020 doi: 10.1002/hep.31301.
    1. Kullak-Ublick GA, Andrade RJ, Merz M, et al. Drug-induced liver injury: recent advances in diagnosis and risk assessment. Gut. 2017;66:1154–1164. doi: 10.1136/gutjnl-2016-313369.
    1. Sarin SK, Choudhury A, Sharma MK, APASL ACLF Research Consortium (AARC) for APASL ACLF working Party et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int. 2019;13(4):353–390. doi: 10.1007/s12072-019-09946-3.

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