High rates of 30-day mortality in patients with cirrhosis and COVID-19

Massimo Iavarone, Roberta D'Ambrosio, Alessandro Soria, Michela Triolo, Nicola Pugliese, Paolo Del Poggio, Giovanni Perricone, Sara Massironi, Angiola Spinetti, Elisabetta Buscarini, Mauro Viganò, Canio Carriero, Stefano Fagiuoli, Alessio Aghemo, Luca S Belli, Martina Lucà, Marianna Pedaci, Alessandro Rimondi, Maria Grazia Rumi, Pietro Invernizzi, Paolo Bonfanti, Pietro Lampertico, Massimo Iavarone, Roberta D'Ambrosio, Alessandro Soria, Michela Triolo, Nicola Pugliese, Paolo Del Poggio, Giovanni Perricone, Sara Massironi, Angiola Spinetti, Elisabetta Buscarini, Mauro Viganò, Canio Carriero, Stefano Fagiuoli, Alessio Aghemo, Luca S Belli, Martina Lucà, Marianna Pedaci, Alessandro Rimondi, Maria Grazia Rumi, Pietro Invernizzi, Paolo Bonfanti, Pietro Lampertico

Abstract

Background & aims: Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities, but its impact on patients with cirrhosis is currently unknown. Herein, we aimed to evaluate the impact of COVID-19 on the clinical outcome of patients with cirrhosis.

Methods: In this multicentre retrospective study, patients with cirrhosis and a confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were enrolled between 1st and 31th March 2020. Clinical and biochemical data at diagnosis of COVID-19 and at the last outpatient visit were obtained through review of medical records.

Results: Fifty patients with cirrhosis and confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or a prolonged stay if already in hospital. Respiratory support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with a model for end-stage liver disease (MELD) score ≥15 increased from 13% to 26% (p = 0.037), acute-on-chronic liver failure and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4-13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. The severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. In patients with cirrhosis, mortality was significantly higher in those with COVID-19 than in those hospitalized for bacterial infections.

Conclusion: COVID-19 is associated with liver function deterioration and elevated mortality in patients with cirrhosis.

Lay summary: Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities. Herein, we assessed its impact on patients with cirrhosis. Infection with COVID-19 was associated with liver function deterioration and elevated mortality in patients with cirrhosis.

Keywords: HBV; HCV; Hepatitis; Hepatocellular carcinoma; Liver transplantation; SARS-CoV-2.

Conflict of interest statement

Conflict of interest Massimo Iavarone: Speaking/Teaching, consultant and advisory board for Bayer, Gilead Sciences, BMS, Janssen, Ipsen, MSD, BTG-Boston Scientific, AbbVie, Guerbet, EISAI; Roberta D'Ambrosio: teaching and speaking for AbbVie, Gilead, MSD; Advisory Board for AbbVie, MSD, Research Grant from Gilead; Alessandro Soria: Speaking/Teaching, consultant and advisory board for AbbVie, MSD, Gilead; Mauro Viganò: speaking and teaching for Fujirebio, Intercept, Gilead; Alessio Aghemo: Advisory Board/Speaker Bureau for: Gilead, AbbVie, Intercept, MSD, Mylan and Alfasigma, Research grants from Gilead and Abbvie; Stefano Fagiuoli: Advisory Board/Speaker Bureau for Gilead, AbbVie, Novartis, MSD, Bayer, Intercept, Kedrion; Pietro Invernizzi: Advisory Board/Speaker Bureau for Gilead, Intercept, Bruschettini, AbbVie, MSD; Pietro Lampertico: Advisory Board/Speaker Bureau for BMS, Roche, Gilead, GSK, AbbVie, MSD, Arrowhead, Alnylam, Janssen, Spring Bank, MYR, Eiger. The other authors declare no conflict of interest. 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
30-day cumulative probability of overall mortality and COVID-19-related or liver-related mortality. (A) 30-day cumulative probability of overall mortality and (B) 30-day cumulative probability of either COVID-19-related or liver-related mortality; survival curves were estimated by the Kaplan-Meier method.
Fig. 2
Fig. 2
30-day cumulative probability of overall mortality according to liver function at COVID-19 diagnosis. 30-day cumulative probability of overall mortality according to (A) MELD ≥15 status at COVID-19 diagnosis and (B) CLIF-OF >9 status at COVID-19 diagnosis; survival curves were estimated by the Kaplan-Meier method with a significance level of p ≤0.05.

References

    1. World Health Organization Novel coronavirus — China. January 12, 2020.
    1. Guzzetta G., Poletti P., Ajelli M., Trentini F., Marziano V., Cereda D., et al. Potential short-term outcome of an uncontrolled COVID-19 epidemic in Lombardy, Italy, February to March 2020. Euro Surveill. 2020;25:2000293.
    1. Istituto Superiore di Sanità “COVID-19 epidemic. 2 April 2020 national update” Appendix to the bulletin with a regional breakdown.
    1. Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X., et al. China Medical Treatment Expert Group for Covid-19 Clinical characteristics of 2019 novel coronavirus infection in China. N Engl J Med. 2020;382:1708–1720.
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
    1. 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;395:507–513.
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., et al. Clinical characteristics of 138 hospitalised patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–1069.
    1. Shi H., Han X., Jiang N., Cao Y., Alwalid O., Gu J., et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis. 2020;20:425–434.
    1. Xu X.W., Wu X.X., Jiang X.G., Xu K.J., Ying L.J., Ma C.L., 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.
    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;8:475–481.
    1. Grasselli G., Zangrillo A., Zanella A., Antonelli M., Cabrini L., Castelli A., et al. COVID-19 Lombardy ICU Network Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA. 2020;323:1574–1581.
    1. Piano S., Brocca A., Mareso S., Angeli P. Infections complicating cirrhosis. Liver Int. 2018;38(S1):126–133.
    1. Premkumar M., Devurgowda D., Dudha S., Maiwall R., Bihari C., Grover S., et al. A/H1N1/09 influenza is associated with high mortality in liver cirrhosis. J Clin Exp Hepatol. 2019;9:162–170.
    1. Park J.H., Choi J., Jun D.W., Han S.W., Yeo Y.H., Nguyen M.H. Low alanine aminotransferase cut-off for predicting liver outcomes; A nationwide population-based longitudinal cohort study. J Clin Med. 2019;8:1445.
    1. European Association for the Study of the Liver EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–460.
    1. Cao Y., Liu X., Xiong L., Cai K. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis. J Med Virol. 2020 doi: 10.1002/jmv.25822.
    1. Zhang C., Shi L., Wang F.S. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. 2020;5:428–430.
    1. Ji D., Qin E., Xu J., Zhang D., Cheng G., Wang Y., et al. Implication of non-alcoholic fatty liver diseases (NAFLD) in patients with COVID-19: a preliminary analysis. J Hepatol. 2020 PII: S0168-8278(20)30206-3.
    1. 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 2020.02.03.9317766.
    1. Sun J., Aghemo A., Forner A., Valenti L. COVID-19 and liver disease. Liver Int. 2020;40:1278–1281.

Source: PubMed

3
Abonner