key: cord-0919879-vaswxlch
authors: Zhan, Ke; Liao, Shengtao; Li, Jinfang; Bai, Yang; Lv, Lin; Yu, Keqi; Qiu, Liewang; Li, Chuanfei; Yuan, Guodan; Zhang, An; Mei, Zhechuan
title: Risk factors in patients with COVID-19 developing severe liver injury during hospitalisation
date: 2020-06-22
journal: Gut
DOI: 10.1136/gutjnl-2020-321913
sha: 8952c41ed9d87899d2e1d09e3d4f62a10da4f5c1
doc_id: 919879
cord_uid: vaswxlch

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Therefore, identification of the risk factors contributing to severe liver injury during hospitalisation is essential for the treatment of COVID-19. The results indicated that the number of T lymphocyte subsets (CD3 + , CD4 + and CD8 + T cells) were significantly reduced in patients with severe liver injury, while the proportion of ritonavir, the number of neutrophils and monocytes, and the production of IL-6 and IL-10 were remarkably increased (online supplementary table 1). Univariate analysis indicated that ritonavir, CD3 + , CD4 + and CD8 + T cells, IL-6 and IL-10 were potential risk factors in patients with COVID-19 with severe liver injury during hospitalisation (p<0.05, table 1); multivariate analysis revealed that ritonavir (OR 5.63, 95% CI 2.86 to 18.63, p<0.001), IL-6 (OR 2.21, 95% CI 1.09 to 4.67, p=0.006), IL-10 (OR 1.78, 95% CI 1.08 to 3.12, p=0.014) and CD4 + T cells (OR 3.24, 95% CI 1.05 to 6.38, p<0.001) were independent risk factors in patients with COVID-19 with severe liver damage (table 1), suggesting that the progression of liver injury was associated with medication, T lymphocyte subsets and inflammatory cytokines.

SARS-CoV-2-mediated liver injury might be a key factor in liver damage. 6 SARS-CoV-2 may directly target ACE2positive cholangiocytes and hepatocytes, further leading to liver cell damage and bile duct cell dysfunction, consequently aggravating liver damage. Dysregulated immune response was observed in patients with COVID-19. 7 Furthermore, previous studies have indicated that the SARS-CoV-2 infection may primarily affect T lymphocytes, particularly CD4 + and CD8 + cells, which are involved in pro-inflammatory responses. 7 8 At present, no specific treatment is available for patients with COVID-19. The commonly used antiviral drugs lopinavir/ritonavir are mainly metabolised in the liver but exhibit side effects such as liver dysfunction. In addition, overdose of ribavirin induces hemolysis and exacerbates tissue hypoxia, leading to the elevation of serum liver enzymes. 9 10 A recent study revealed higher proportion in patients with liver dysfunction following the treatment with lopinavir/ritonavir during hospitalisation. 5 In conclusion, potential risk factors in patients with COVID-19 developing severe liver injury were ritonavir, elevated IL-6 and IL-10, and reduced CD4 + T cells. In addition, the underlying mechanisms of liver injury in patients with COVID-19 involve immune response, cytokine production, drug-induced liver injury and potential SARS-CoV-2-mediated liver damage (figure 1). Therefore, during the treatment of COVID-19, liver function, inflammatory cytokines and T lymphocyte subsets should be closely monitored, and drug-induced liver damage could be considered in clinical practice.

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