Abnormal Liver Function Tests Predict Transfer to Intensive Care Unit and Death in COVID-19

Salvatore Piano; Andrea Dalbeni; Elia Vettore; Devis Benfaremo; Massimo Mattioli; Carmine G. Gambino; Viviana Framba; Lorenzo Cerruti; Anna Mantovani; Andrea Martini; Michele M. Luchetti; Roberto Serra; Annamaria Cattelan; Roberto Vettor; Paolo Angeli

Disclosures

Liver International. 2020;40(10):2394-2406. 

In This Article

Abstract and Introduction

Abstract

Background: The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID-19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non-critically ill patients with COVID-19.

Methods: In this multicentre, retrospective study, we collected data about 565 inpatients with COVID-19. Data on LFTs were collected at admission and every 7 ± 2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU).

Results: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20% vs 8%; P < .001), acute kidney injury (22% vs 13%, P = .009), need for mechanical ventilation (14% vs 6%; P = .005) and mortality (21% vs 11%; P = .004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR = 3.53; P < .001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint.

Conclusions: LFTs abnormality is common at admission in patients with COVID-19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.

Introduction

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly emerged as a relevant threat for humans worldwide.[1] The main clinical feature of COVID-19 is pneumonia, which is characterized by a high mortality rate, however, increasing data suggest that COVID-19 is a systemic disease affecting also other organs/systems including liver, heart, kidney and coagulation.[2–5] An increase in liver function tests (LFTs) has been found in patients with COVID-19, ranging 14%-75%.[2,3,6–11] Some studies found higher levels of transaminases in patients with severe COVID-19 pneumonia and in patients dying for COVID-19.[2,11–13] The clinical relevance of LFTs abnormalities has been controversial, with some studies suggesting its association with the severity of COVID-19 pneumonia, whereas others not.[9,14] Some limitations affected those studies involving the lack of information about concomitant or previous use of hepatotoxic drugs among the others. Overall, there is a paucity of studies assessing the prevalence, the pattern (hepatocellular, cholestatic, mixed) and the clinical impact of LFTs, in particular in Caucasian patients. On clinical ground, it is still uncertain whether LFTs abnormalities should be considered a marker of severity of COVID-19 or not. Thus, the aim of this study was to assess the prevalence, the clinical features and the clinical impact of abnormal LFTs in hospitalized, non-critically ill patients with COVID-19.

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