Since the start of the COVID-19 pandemic, several studies have described the disease characteristics including different organ injuries and particularly liver injury.[1–7] Several mechanisms have been suggested, one being direct liver toxicity through angiotensin-converting enzyme 2 (ACE-2) receptors expressed in cholangiocytes. Also, sepsis induced by COVID-19 may promote cytokine storm and more specifically Interleukin-6 production which regulates hepatic homeostasis and liver regeneration. Ultimately, COVID-19-specific drugs may induce liver injury.
To our best knowledge, this is the first study exploring liver abnormalities in European COVID-19 patients. In our study, two-thirds of patients had abnormal liver tests on admission which is slightly higher than reported previously.[1,2,4,6] This is likely to be due to the different and older, more comorbid population who had a higher prevalence of chronic liver disease, diabetes, cardiovascular diseases and arterial hypertension compared to previous Chinese studies.[1,12] Although our patients did not have a higher body mass index (BMI) than Chinese cohort, we observed a higher prevalence of severe pneumonia upon admission in our study which may explain higher prevalence of liver tests abnormalities on admission. Only a few of our patients (3.8%) had underlying liver disease, and there were no significantly different comorbidities (alcohol consumption or metabolic syndrome) between the two groups of patients with or without abnormal liver tests on admission, suggesting that liver changes may be COVID-19 related and not due to pre-existing liver disease. However, we had little information about viral status (hepatitis B and C viruses) in the whole population, since viral screening does not currently form part of the management. Also drug-induced liver injury (DILI) could be ruled out as abnormal liver tests pre-existed to specific COVID-19 medication. Whether SARS-CoV-2 directly infects liver cells is unclear and further studies including liver biopsy specimens may be needed. Patients with abnormal liver test on admission were more frequently directly admitted to ICU, which might suggest that these patients had more severe COVID-19 disease at presentation. One may expect that it was related to time delay of disease evolution, but we failed to find any difference in elapsed time from symptoms onset to admission to the hospital between the two groups. Nevertheless, abnormal liver tests on admission, together with CRP and age, were independent predictive risk factors for in-hospital aggravation also reported by Cai et al. Furthermore, abnormal liver tests on admission were independently associated with in-hospital mortality that underlines once again its reliability to the disease severity. Several studies have linked the disease severity to SARS-CoV-2 viral load[13,14] but further studies are needed to confirm this hypothesis.
The severity of liver damage was not the main clinical issue in this cohort since the biological abnormalities were moderate in our study; however, these liver abnormalities could be a surrogate marker for the severity of the viral infection and the risk of death. The mechanisms of liver injury in COVID-19 require further study. We could observe that ACEI/ARB exposure was not associated with abnormal liver tests on admission nor with clinical outcomes which supports actual recommendations to continue them during COVID-19 pandemic.
Our study is limited by the relatively small sample size and its retrospective nature. Information regarding the potential liver toxicity due to COVID-19 experimental drugs was not assessed. Nevertheless, this preliminary study conducted in a European population confirms a high prevalence of abnormal liver parameters on admission reflecting severe disease and higher in-hospital mortality in COVID-19 patients.
ACE-2, angiotensin-converting enzyme 2; ALP, alkaline phosphatase; ALT, alanine transaminase; BMI, body mass index; CEI, angiotensin-converting enzyme inhibitors; CI, confidence interval; COVID-19, Coronavirus disease 2019; CRP, C-reactive protein; CT, computed tomography; CU, intensive care unit; DILI, drug-induced liver injury; GGT, gamma-glutamyl transferase; OR, odds ratio; RB, angiotensin receptor blockers; RT-PCR, reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; SD, standard deviation; ST, aspartate aminotransferase; TBil, total bilirubin; ULN, upper limit of normal.
Liver International. 2020;40(8):1860-1864. © 2020 Blackwell Publishing