Dear Editor:
Dr Fan et al1 assessed the clinical characteristics of corona virus disease 2019 (COVID-19) in 148 patients with liver damage and found that more than one-third of patients admitted to the hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection had abnormal liver function, and 48.4% of patients with normal liver function had liver injury after admission, with a higher proportion in patients receiving lopinavir/ritonavir. Although the article by Fan et al provides valuable information for clinical treatment in COVID-19, we still have some concerns about it.
First, because patients were from a single, large city in China, these findings cannot be generalized to rural communities or other regions. Thus, selection bias cannot be entirely excluded. Furthermore, the data of other causes of liver injury in the patients progressing to liver injury, such as herbal medicines or other drugs used as self-medication before developing COVID-19 pneumonia, were not available for patients in current study. However, since the COVID-19 outbreak in China in December 2019, discussion about COVID-19 has spread rapidly on the Internet and has quickly become the focus of worldwide attention. Shanghai is one of the most developed cities in China, and access to the Internet is widespread, which means many in the population would have a high degree of awareness of the disease. Most patients (>70%) went to the hospital within 5 days after the onset of disease symptoms and rarely used over-the-counter medicine to self-treat because medical insurance is widely available in Shanghai. Hence, although the data on herbs and other drugs used as self-medication before developing COVID-19 pneumonia were not available in this study, their influence on the results cannot be ignored.
Second, high levels of positive end-expiratory pressure might contribute to liver injury in patients with COVID-19. Previous studies have shown that high levels of positive end-expiratory pressure can contribute to hepatic congestion by increasing right atrial pressure and impeding venous return.2 However, whether the COVID-19 patients admitted to hospital with liver blood test abnormalities received mechanical ventilation remained unclear in current study. Furthermore, lymphocytes are important for inhibiting overactive innate immune responses during viral infection. Typical lymphopenia during SARS-CoV-2 infection may result in increases in interleukin 6, interleukin 10, and interferon-γ levels and aggravated inflammatory responses, leading not only to pulmonary injury but also the injury of non-pulmonary organs including the liver.3 A study by Lu et al4 investigated the risk factors involved with hepatic injury in patients with COVID-19 and found that lymphopenia and C-reactive protein level were independently associated with liver injury. However, there was no statistical difference between abnormal and normal groups in lymphopenia; the cause of these results that contradicted the data of Lu et al is also still unknown in this study.
Another issue is that the COVID-19 patients have been confirmed to tend to have underlying liver diseases, including nonalcoholic fatty liver disease, alcoholic 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 unknown in this study. Preliminary data reported by Zhang et al5 indicate that 2%–11% of patients with COVID-19 had liver comorbidities, and whether the results in this study contradict the data of Zhang et al was unclear in this study. In addition, remdesivir treatment during COVID-19 can also induce liver impairment. In an article 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, had elevated liver enzymes.6 However, this issue has not been mentioned in the current study, and the authors should give some interpretation and explanation of these data.
Last, the authors did not apply the definition of drug-induced liver injury from the European Association for the Study of the Liver Clinical Practice Guidelines,7 because currently there was no evidence indicating that the abnormal liver injury during hospitalization was fully induced by the drugs used.
Acknowledgments
The authors thank Fuchao Chen, Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, P.R. China, for providing relevant literature.
Footnotes
Conflicts of interest The authors disclose no conflicts.
Funding Supported by grants from the National Natural Science Foundation of China (31770381).
References
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