We read with interest the work by Weber et al
1 reporting that severe liver failure was observed in a patient during SARS-CoV-2
infection. They suggested that close monitoring of liver function is necessary, and
further investigation is required to elucidate the risk factors for liver failure
in patients with COVID-19. Previous studies have indicated that liver injury could
affect the prognosis of patients with COVID-19, and mortality rate was significantly
increased in patients with severe liver injury.2 3 However, the risk factors in patients
with COVID-19 developing severe liver injury during hospitalisation have not been
thoroughly investigated. Thus, in this study, patients with COVID-19 were recruited
to identify the risk factors in patients with COVID-19 with severe liver injury.
A total of 192 patients diagnosed with COVID-19 were consecutively hospitalised at
Chongqing Public Health Medical Center from January to March 2020, and 12 patients
with existing liver disease had been excluded in this study. Liver injury was detected
in 75 (39.06%) enrolled patients at admission and 133 (69.27%) during hospitalisation,
respectively. Interestingly, liver injury was observed in 25 out of 29 (86.21%) patients
with severe COVID-19. In consistence with our findings, Qi et al
4 revealed that 45.71% of the patients had liver injury at admission; furthermore,
Fan et al
5 reported that 48.4% of the patients with normal liver function developed liver injury
during hospitalisation, suggesting that a high percentage of patients with COVID-19
have liver injury.
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.
10.1136/gutjnl-2020-321913.supp1
Supplementary data
Table 1
Identification of putative risk factors in patients with COVID-19 developing severe
liver injury during hospitalisation
Variable
Univariable OR (95% CI)
P value
Multivariable OR (95% CI)
P value
Ritonavir
5.24 (0.69 to 16.39)
<0.001
5.63 (2.86 to 18.63)
<0.001
IL-6, pg/mL
2.13 (1.08 to 3.21)
<0.001
2.21 (1.09 to 4.67)
0.006
IL-10, pg/mL
1.82 (1.03 to 2.85)
0.004
1.78 (1.08 to 3.12)
0.014
CD4+ T cell, per μL
2.90 (1.85 to 5.96)
<0.001
3.24 (1.05 to 6.38)
<0.001
CD8+ T cell, per μL
1.88 (1.03 to 3.15)
0.005
CD4+ T/CD8+ T cell
1.08 (0.99 to 1.35)
0.163
CD3+ T cell, per μL
0.43 (0.19 to 0.88)
0.034
Neutrophil count, ×109/L
1.11 (1.02 to 1.25)
0.077
Monocyte count, ×109/L
3.41 (1.05 to 17.99)
0.106
SARS-CoV-2–mediated liver injury might be a key factor in liver damage.6 SARS-CoV-2
may directly target ACE2-positive 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.
Figure 1
Host immune responses and potential liver injury during the viral infection of SARS-CoV-2.