Clinical characteristics of COVID-19 patients with abnormal liver tests.

To the Editor:

We read with great interest the research article “COVID-19: Abnormal liver function tests” by Cai et al. published recently in Journal of Hepatology. The authors assessed the clinical characteristics of COVID-19 in patients with abnormal liver tests and found that patients with abnormal liver tests, especially in hepatocyte type or mixed type, were at higher risk of progressing to severe disease. They found that liver impairment in patients with COVID-19 was mainly related to certain medications used during hospitalization. This study is important and interesting; however, there are still some concerns about it.

First, selection bias cannot be entirely excluded, although it is likely to be minimal as all patients with COVID-19 (severe group and not-severe group) during the study period were included and matched for age, sex, body mass index, illness severity, some biochemistry indicators and the admission time point. However, whether the included patients had taken medications before admission was still completely unclear in this study. It is noteworthy that mild liver test derangement would also be present at baseline in confirmed cases of COVID-19 who had received medications such as antipyretics (acetaminophen), antibiotics (macrolides, quinolones) or steroids before admission to hospital.

Furthermore, it has been reported that another possible contributing factor for hepatic injury in COVID-19 patients may be the high levels of positive end expiratory pressure that can cause hepatic congestion by increasing right atrial pressure and impeding venous return. However, whether the patients with COVID-19 received mechanical ventilation remained unclear in the current study. Additionally, it has been found that remdesivir treatment during COVID-19 can also induce liver impairment. In a paper describing the first 12 patients with COVID-19 in the United States, the 3 hospitalized patients who received remdesivir at the time of clinical worsening reported elevated liver enzymes. However, this issue has not been mentioned in the current study, and the authors should give some interpretation and explanation of these data in the text.

Another issue is that the authors have found that patients also tended to have underlying liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease, and chronic hepatitis B, and had cough as an initial symptom; however, the specific ratio of COVID-19 patients with liver comorbidities was still unknown in this study. Preliminary data reported by Zhang C et al. indicate that 2–11% of patients with COVID-19 had liver comorbidities, and whether the results in this study contradict the data of Zhang C et al. is not clear. If these results are contradictory, we would presume that this is caused by differences in the study populations; the patients in the current study were mainly aged less than 50 years old and more than half of the patients were from Hubei. Furthermore, the exact cause of pre-existing liver conditions has not yet been outlined in this study.

In a study of 1,099 patients with laboratory confirmed COVID-19, 23 (2.1%) patients had hepatitis B infection. Severe cases were more likely to have hepatitis B infection (2.4% vs. 0.6%) than non-severe cases. SARS patients with HBV/HCV infection were more prone to develop severe hepatitis. These data suggest more intensive immunotherapy may be required to minimize COVID-19, an issue that warrants further study. However, in patients with COVID-19 with autoimmune hepatitis, the effects of administration of glucocorticoids on disease prognosis is unclear. Given the expression of the ACE2 receptor in cholangiocytes, whether infection with SARS-CoV-2 aggravates cholestasis in patients with primary biliary cholangitis, also needs to be studied.

Finally, as a cohort study, this research can reflect the “real-world” findings and further support the conclusion, but the cohort data may be influenced by bias due to the patient selection process. Therefore, a large-scale study should be conducted in the future.

Financial support

This work was supported by grants from the (31770381).

Authors' contributions

CP and BH Zhou had the idea for and designed the study, received the grant supports and had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. CP contributed to the writing and statistical analysis of the report. All authors contributed to data acquisition, data analysis, or data interpretation, and reviewed and approved the final version.

Conflict of interest

The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.