key: cord-0715923-hisla4gp
authors: Cai, Qingxian; Xu, Lin; Chen, Jun
title: Reply to “Liver tests abnormalities in COVID-19: trick or treat?”
date: 2020-07-04
journal: J Hepatol
DOI: 10.1016/j.jhep.2020.06.041
sha: 45f199c58ba291df1696513ca0f48b612913a0b7
doc_id: 715923
cord_uid: hisla4gp

nan

Foundation.

The authors declare no conflicts of interest that pertain to this work.

Electronic word count: 626

Number of Tables: 1 Author's contributions: J Chen designed the study, received the grant support, had full access to all data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. QX Cai and L Xu contributed to the writing and statistical analysis of the report. All authors contributed to data acquisition, data analysis, and data interpretation, and reviewed and approved the final version of the manuscript.

To the Editor:

We thank the Humanitas COVID-19 Task Force for their interest in our manuscript and for their thoughtful comments.

In their letter, Vespa et al., pointed out that our finding of a 41% prevalence of elevated liver function tests (LFTs) at admission appears to be higher than rates reported throughout Asia and particularly, the rates reported in their cohort. We reviewed and summarized the articles mentioned in their letter (Table 1 ). [1] [2] [3] [4] [5] [6] We found that the prevalence of elevated LFTs at admission in our study was significantly lower than that reported by Vespa et al [2] , as refer to ALT (54/417 vs 78/292, P<0.001), GGT (68/417 vs 106/292, P<0.001) or ALP (20/417 vs 28/292, P=0.012) and higher for TBIL (97/417 vs 31/292, P<0.001), but comparable with other patient series from Asia [3] [4] [5] [6] . In fact, due to the differences in the cut-off values of elevated LFTs, underlying liver disease, and demographic factors, the prevalence of elevated LFTs in patients with COVID-19 at admission may vary widely. Of note, it has been observed that the prevalence of elevated LFTs would increase in the course of COVID-19, as seen in our study, [2] which found that the time from disease onset to hospitalization significantly influenced the elevated rate of LFTs at admission.

Because of the limited medical resources available during the beginning of the pandemic, many hospitals in high pandemic areas may have only received patients with severe disease, which would result in seeing patients with more severe liver injury. In our study, all laboratory-confirmed COVID-19 patients who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 were included. Elevated LFTs were defined as the following criteria: So far, older age has been acknowledged as one of the most important risk factors for deterioration due to COVID-19. [7] Others at highest risk for severe COVID-19 are people with certain underlying conditions, including hypertension，cardiovascular disease，diabetes，chronic respiratory disease, cancer, renal disease, and obesity. [8] Some studies have also reported that abnormal LFTs were associated with overall prognosis. [3, 4] Fan et al., for example, reported that baseline abnormal liver function was associated with prolonged hospital stay. [3] In a recent systematic review, Kunutsor and Laukkanen conducted a meta-analysis of sixteen retrospective cohort studies based in China and concluded that elevated levels of liver injury markers, particularly, aminotransferases, may be associated with progression to severe disease or death [9] .

As seen in Table 1 , the cohorts with higher mortality usually had more severe LFTs changes.

In the study by Vespa et al., [2] elevated ALP above 150 UI/L was associated with deterioration (p=0.048) and became non-significant after adjustment for age and sex (P=0.13). In our study, GGT was substantially elevated at admission, whereas the increase in ALP was not pronounced in patients with COVID-19. This finding was consistent with other cohorts. [3] [4] [5] [6] The patients with COVID-19 showed elevated GGT levels and normal ALP, which may controvert the hypothesis that SARS-CoV-2 directly injures the cholangiocytes. Therefore, we agree that ALP or GGT elevation may just be a marker of patient frailty or represent a stronger systemic inflammatory response to SARS-CoV-2 infection, rather than a sign of cholestatic liver injury. Liver and lung injuries share the same underlying mechanism, which may be directly or indirectly induced by SARS-CoV-2 infection. Laboratory liver function tests should thus be interpreted with caution and always in the context of a complex, multi-organ disease. ALT, alanine aminotransferase; AST, aspartate transaminase; TBIL, total bilirubin abnormal; GGT, gamma glutamyl-transpeptidase; ALP, alkaline phosphatase; ICU, intensive care unit; n/a, not available.

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