key: cord-0893535-ni94qi4r
authors: Vespa, Edoardo; Pugliese, Nicola; Piovani, Daniele; Capogreco, Antonio; Danese, Silvio; Aghemo, Alessio
title: Liver tests abnormalities in COVID-19: trick or treat?
date: 2020-05-27
journal: J Hepatol
DOI: 10.1016/j.jhep.2020.05.033
sha: 2c9c41851895854167e7714b58107d4d497a1f4c
doc_id: 893535
cord_uid: ni94qi4r

nan

Editor, Professor Paolo Angeli Dear Paolo, included is a revised version of the letter to the editor in response to the paper by Cai et al. We have included the reviewer's comments which we think have improved our letter. We hope that it now suitable for publication in the Journal of Hepatology. Financial support: The authors declare no financial support relevant to the study.

We read with interest the recent study by Cai et al [1] , which describes the role of liver function tests (LFTs) in a population of hospitalized patients with COVID-19. The authors' finding of a 41% prevalence of patients at admission with at least one elevated LFT appears to be higher than those previously reported in other cohorts of patients from Asia (25-30%) [2, 3] . Similarly, when analyzing a consecutive cohort of 292 RT-PCR-confirmed Covid-19 patients admitted to our center until 30 March 2020, we also noticed that the prevalence of elevated LFTs was lower in our cohort.

Increased aspartate-transaminase (AST) or alanine-transaminase (ALT) values >50 UI/L were seen in 18.5% and 26.7% of patients respectively. While an increase in gamma glutamyltranspeptidase (GGT) >55 U/L was observed in 36.2%, alkaline phosphatase (ALP) >150 U/L in 9.6%, and total bilirubin > 1.2 mg/dl in 10.6% [4] . Pre-existing advanced liver disease was reported in 6 patients (2%), while antiviral treatment with Lopinavir/Ritonavir was administered in 250 patients (85.9%).

In our case series we could not replicate the finding by Cai et al that patients presenting with abnormal LFTs at admission evolve towards a more severe form of pneumonia. Clinical deterioration occurred in 82 patients (28.1%), with 27 (9.2%) admitted to Intensive Care Unit (ICU) and 56 (19.2%) dying during observation. By performing univariable Kaplan-Meier survival analyses for any of the LFTs at admission, with the aim to assess factors associated with death or admittance to the ICU , we found none of hepatocellular injury markers (AST or ALT) to be associated with these endpoints. No significant association was also found with GGT and TBIL.

The only predictive factor associated with deterioration was the elevation of ALP above 150 UI/L (p= 0.048) (figure 1). This data is in line with other studies which reported a high prevalence of LFTs abnormalities in Covid-19 but failed to demonstrate an association with worse outcomes [3] .

Interestingly, our observation on the clinical value of ALP as a marker of poor prognosis is in contrast with the finding by Cai and colleagues that the risk of progression to severe disease was associated with hepatocellular (AST and/or ALT >3 ULN) or mixed (a combination of AST/ALT >3 ULN and ALP/GGT >2 ULN) pattern of LFTs elevation, rather than a cholestatic pattern. While the prognostic value of ALP could be explained by sars-cov-2 tropism for liver and ACE2 expression in hepatocytes and cholangiocytes, we cannot exclude isolated ALP 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. Supporting this hypothesis, is a recent study from Asia showing a correlation between the increase in LFTs and other inflammatory markers [5] .

In conclusion, we think that although LFTs alterations are common in hospitalized Covid-19 patients, it is still unclear whether they carry any prognostic value. Laboratory liver function tests should thus be interpreted with caution and always in the context of a complex multi-organ disease. 

Characteristics of Liver Tests in COVID-19 Patients

Clinical Features of COVID-19-Related Liver Damage

Liver impairment in COVID-19 patients: a retrospective analysis of 115 cases from a single center in Wuhan city

Covid-19 digestive system involvement and clinical outcomes in a large academic hospital in

Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: A retrospective study