Clinical Characteristics of Non-ICU Hospitalized Patients With Coronavirus Disease 2019 and Liver Injury

A Retrospective Study

Hansheng Xie; Jianming Zhao; Ningfang Lian; Su Lin; Qunfang Xie; Huichang Zhuo

Disclosures

Liver International. 2020;40(6):1321-1326. 

In This Article

Discussion

This retrospective study found that nearly 1/3 non-ICU hospitalized patients with COVID-19 had liver injury. Males and those who had higher levels of white blood cells, neutrophils, CRP and CT lesions are more likely to have liver injury.

Previous studies have found that liver injury was common in critically ill patients with COVID-19.[4,8–10] Autopsy results of patients with COVID-19 revealed degeneration of hepatocytes, focal necrosis with neutrophil infiltration; lymphocytic and monocyte infiltration in the hepatic manifold area and microthrombosis. The results of the study by Huang et al suggested that the median values of ALT and AST in the non-ICU group were 27.0 (19.5–40.0) and 34.0 (24.0–40.5) U/L, respectively, which were at normal range in ICU group; the median values of ALT and AST in the group were 49.0 (29.0 to 115.0) and 44.0 (30.0 to 70) U/L respectively.[9] The study failed to investigate the cause of elevated serum transaminase. Wang et al[9] found that the median AST of ICU patients was 52 (30–70) U/L, but the study did not explore the cause of abnormal AST in the ICU group. In this study, we focused on non-ICU residents. Although the median values of ALT and AST were in the normal range, nearly one-third patients had elevated ALT or AST. The clinical findings suggested that even in non-critical COVID-19 patients, liver injury was common, while most patients had slight elevated aminotransferases and good prognosis.

The mechanisms of liver injury that occurred during 2019 new coronavirus (2019-nCoV) infection remain largely unclear.[4] To explore the reasons of liver injury in patients, we compared the clinical characteristics of patients with and without liver injury. To avoid the impact of previous liver disease on the results of the study, we excluded patients with a previous history of liver disease during the patient enrolment process. Although the median time from symptom onset to hospitalization was 12 days, none of these patients had undergone regular antiviral therapy, so possibility of liver injury in these patients resulting from drug may be excluded. COVID-19 with liver injury group had increased white blood cells, neutrophils and CRP. The results indicated that the levels of body's inflammation may have certain effects on the liver function of COVID-19. The severity of lung CT lesions can reflect the severity of COVID-19 to a certain extent. In this study, we found that COVID-19 with liver injury had higher CT score; and CT score was the predictor factor of liver injury in COVID-19. Although it is not confirmed whether there is a causal relationship between changes in lung CT and liver injury, the above results suggest that patients with severe imaging lesions need to undergo close monitoring of liver function to identify patients with liver damage for early intervention. Liver injury was associated with prolonged hospital stay in our study, so liver damage may be related to prognosis of patients with COVID-19.

Angiotensin converting enzyme II (ACE2) may also be the main receptor for 2019-nCoV.[11] Single-cell sequencing showed that ACE2 was mainly expressed in bile duct epithelial cells in normal liver tissues, but very low in hepatocytes; But ACE2 expression is upregulated in a mouse model of acute liver injury.[12] Proliferation of bile duct epithelium in the manifold area is involved in liver damage repair. This phenomenon may suggest that ACE2-expressing bile duct epithelial cells dedifferentiate and proliferate and become new liver cells. During this compensatory process, some neonatal hepatocytes still retain the characteristics of expressing ACE2 and are susceptible to 2019-nCoV.[13] This may be the cause of liver injury in COVID-19. The study found a higher proportion of male in COVID-19 with liver damage. Whether it is related to the number of ACE2 receptors in male hepatocytes remains unclear. It is worth to further investigate in the future.

The study had some limitations. (a) The study was a single-centre, retrospective study with a small sample size. The nature of this study might compromise the conclusion. (b) Underlying liver diseases were the major confounding factors in this study. Although we tried to eliminate the influence of chronic liver disease by excluding viral hepatitis, alcoholic hepatitis or malignancy, we still could not completely rule out the impact of non-alcoholic fatty liver disease. The diagnosis of fatty liver disease requires the radiology examination in liver, which cannot be widely carried out when the medical resource is limited during the outbreak of COVID-19. However, the liver enzymes after treatment between patients with and without liver injury were not significantly different, suggesting the elevated liver enzymes on admission were more likely to be resulted from COVID-19 infection than any other underlying liver disease.

The results of this retrospective study suggested that COVID-19 with liver injury in non-ICU hospitalized patients was common, and it may be related to the degree of CT lesions in the lung. Therefore, the close monitoring and evaluation of liver function in patients with severe pulmonary imaging lesions should be considered.

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