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Clinical course and risk factors for mortality of COVID-19 patients with pre-existing cirrhosis: a multicentre cohort study
  1. Xiaolong Qi1,
  2. Yanna Liu1,
  3. Jitao Wang2,
  4. Jonathan A Fallowfield3,
  5. Jianwen Wang4,
  6. Xinyu Li5,
  7. Jindong Shi6,
  8. Hongqiu Pan7,
  9. Shengqiang Zou7,
  10. Hongguang Zhang7,
  11. Zhenhuai Chen8,
  12. Fujian Li8,
  13. Yan Luo9,
  14. Mei Mei9,
  15. Huiling Liu9,
  16. Zhengyan Wang10,
  17. Jinlin Li10,
  18. Hua Yang11,
  19. Huihua Xiang12,
  20. Xiaodan Li13,
  21. Tao Liu14,
  22. Ming-Hua Zheng15,
  23. Chuan Liu1,
  24. Yifei Huang1,
  25. Dan Xu1,
  26. Xiaoguo Li1,
  27. Ning Kang1,
  28. Qing He16,
  29. Ye Gu17,
  30. Guo Zhang18,
  31. Chuxiao Shao19,
  32. Dengxiang Liu2,
  33. Lin Zhang20,
  34. Xun Li21,
  35. Norifumi Kawada22,
  36. Zicheng Jiang23,
  37. Fengmei Wang24,
  38. Bin Xiong25,
  39. Tetsuo Takehara26,
  40. Don C Rockey27
  41. for the COVID-Cirrhosis-CHESS Group
  1. 1 CHESS Center, Institute of Portal Hypertension, The First Hospital of Lanzhou University, Lanzhou, China
  2. 2 CHESS-COVID-19 Group, Xingtai People’s Hospital, Xingtai, China
  3. 3 Centre for Inflammation Research, University of Edinburgh MRC Centre for Inflammation Research, Edinburgh, UK
  4. 4 Department of Tuberculosis and Respiratory, Wuhan Jinyintan Hospital, Wuhan, China
  5. 5 Department of Infectious Disease, Shanghai Fifth People's Hospital of Fudan University, Shanghai, China
  6. 6 Department of Respiratory Medicine, Shanghai Fifth People's Hospital of Fudan University, Shanghai, China
  7. 7 Department of Infectious Diseases and Critical Care Medicine, The Affiliated Third Hospital of Jiangsu University, Zhenjiang, China
  8. 8 Department of Respiratory Medicine, The People's Hospital of Baoding, Baoding, China
  9. 9 Department of Gastroenterology, Tianjin Haihe Hospital, Tianjin, China
  10. 10 Department of Respiratory Medicine, Suizhou Hospital, Hubei University of Medicine, Suizhou, China
  11. 11 Department of Respiratory Medicine, Minda Hospital Affiliated to Hubei University for Nationalities, Enshi, China
  12. 12 Department of Radiology, Minda Hospital Affiliated to Hubei University for Nationalities, Enshi, China
  13. 13 Department of Infectious Disease, The Central Hospital of Enshi Tujia And Miao Autonomous Prefecture, Enshi, China
  14. 14 Department of Infectious Disease, The Central Hospital of Lichuan, Enshi, China
  15. 15 MAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
  16. 16 CHESS-COVID-19 Group, The Third People's Hospital of Shenzhen, Shenzhen, China
  17. 17 CHESS-COVID-19 Group, The Sixth People’s Hospital of Shenyang, Shenyang, China
  18. 18 CHESS-COVID-19 Group, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
  19. 19 CHESS-COVID-19 Group, Zhejiang University Lishui Hospital and Lishui Central Hospital, Lishui, China
  20. 20 Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
  21. 21 The First Hospital of Lanzhou University, Lanzhou, China
  22. 22 Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
  23. 23 Department of Infectious Disease, Ankang Central Hospital, Ankang, China
  24. 24 Department of Gastroenterology and Hepatology, Tianjin Second People’s Hospital, Tianjin, China
  25. 25 Department of Radiology, Wuhan Union Hospital, Wuhan, China
  26. 26 Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
  27. 27 Division of Gastroenterology and Hepatology, Medical University South Carolina, Charleston, South Carolina, USA
  1. Correspondence to Professor Xiaolong Qi, CHESS Center, Institute of Portal Hypertension, Lanzhou University First Affiliated Hospital, Lanzhou 730000, China; qixiaolong{at}vip.163.com; Dr Bin Xiong, Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; herr_xiong{at}126.com

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COVID-19 has rapidly become a global challenge.1 We read with interest the article by Bezzio et al 1 that reported the characteristics and outcomes of COVID-19 patients with pre-existing IBD. Patients with pre-existing cirrhosis, who have immune dysfunction and poorer outcomes from acute respiratory distress syndrome (ARDS) than patients without cirrhosis, are also considered a high-risk population for COVID-19.2 3In previous studies, the proportion of COVID-19 patients with pre-existing liver conditions ranged from 2% to 11%.2 However, the clinical course and risk factors for mortality in these patients has not yet been reported.

This retrospective multicentre study (COVID-Cirrhosis-CHESS, ClinicalTrials.gov NCT04329559) included consecutive adult patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pre-existing cirrhosis from 16 designated hospitals in China between 31 December 2019 and 24 March 2020. Patient characteristics are summarised in table 1. Twenty-one COVID-19 patients with pre-existing cirrhosis (Child-Pugh class A, B and C in 16, 3 and 2 patients, respectively) were included in the analysis. The median age was 68 years; 11 (52.4%) were male. Most patients had compensated cirrhosis (81.0%) and chronic HBV infection was the most common aetiology (57.1%). Comorbidities other than cirrhosis were present in most patients (66.7%). In previous studies, older age, male sex and pre-existing comorbidities were associated with higher risk of mortality for COVID-19.4 5 Here, there were no significant differences between survivors (n=16) and non-survivors (n=5) in age, sex, comorbidities, aetiology of cirrhosis, stage of cirrhosis, Child-Pugh class, Model for End-stage Liver Disease (MELD) score, interval between onset and admission, or onset symptoms of COVID-19. Comorbidities have been associated with adverse outcomes in cirrhosis,6 but our analysis did not show clear prognostic associations—possibly due to the small size and narrow composition of the study population.

Table 1

Clinical, laboratory and radiographic findings on admission

Fever and cough were the most common symptoms on admission, similar to previous studies of COVID-19 among general populations.7 8 Elevations in aspartate transaminase, alanine aminotransferase and gamma-glutamyl transferase levels were present in 8 (38.1%), 5 (23.8%) and 5 (23.8%) patients, respectively. Leucopenia, lymphopenia and thrombocytopenia occurred in 8 (38.3%), 15 (71.4%) and 8 (38.1%) patients, respectively. Although abnormal haematological indices and portal hypertension are common in cirrhosis, patients with COVID-19 who died had lower total lymphocyte and platelet counts, and also higher direct bilirubin levels than patients who survived (p=0.040, 0.032 and 0.006, respectively). These findings are consistent with previous studies in the general COVID-19 population.9 10

Treatment and complications occurring during hospitalisation are summarised in table 2. The frequency of ARDS and GI bleeding were higher in non-survivors than survivors (100.0% vs 6.3%, p<0.001, and 60.0% vs 6.3%, p=0.028, respectively). Of the five non-survivors, all patients developed ARDS and two patients progressed to multiple organ dysfunction syndrome. One patient who died developed clear evidence of acute-on-chronic liver failure.

Table 2

Treatment, complications and outcomes

In contrast to Western populations, the main cirrhosis aetiology in this China-based study was chronic HBV, so it is unclear if our findings are generalisable to other geographic regions. To further define the clinical course of COVID-19 patients with pre-existing cirrhosis and confirm risk factors for mortality, larger prospective studies comprising patients with different cirrhosis aetiologies are expected.

In conclusion, we provide the first report of the demographic characteristics, comorbidities, laboratory and radiographic findings, and clinical outcomes in SARS-CoV-2-infected patients with pre-existing cirrhosis. The cause of death in most patients was respiratory failure rather than progression of liver disease (ie, development of acute-on-chronic liver failure). Lower lymphocyte and platelet counts, and higher direct bilirubin level might represent poor prognostic indicators in this patient population.

Acknowledgments

We thank the great support and critical comments of Xavier Dray (Saint Antoine Hospital, APHP & Sorbonne University, France), Mingkai Chen (Renmin Hospital of Wuhan University, China) and Jiahong Dong (Beijing Tsinghua Changgung Hospital, China).

References

Footnotes

  • XQ, YL, JW and JAF are joint first authors.

  • XQ, TT and DCR are joint senior authors.

  • Correction notice This article has been corrected since it published Online First. Dr Fallowfield's name has been amended.

  • Contributors Concept and design: XQ; acquisition and interpretation of data: BX, JW, XL, JS, HP, SZ, HZ, ZC, FL, YL, MM, HL, ZW, JL, HY, HX, XL, TL, M-HZ, CL, YH, DX, QH, YG, GZ, CS, DL, LZ, XL, ZJ, FW; drafting of the manuscript: YL, JW, XQ; critical revision of the manuscript: DR, JF, TT, NK; final approval: all authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Study approvals were granted by institutional ethics committees and written informed consent was waived.

  • Provenance and peer review Not commissioned; internally peer reviewed.