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. 2020 May 5;24:190. doi: 10.1186/s13054-020-02924-4

Liver injury in critically ill patients with COVID-19: a case series

Filipe S Cardoso 1,, Rui Pereira 1, Nuno Germano 1
PMCID: PMC7198236  PMID: 32366282

Dear Editor,

Almost all reports on liver injury in patients with 2019 coronavirus disease (COVID-19) found blood liver tests to be frequently abnormal, especially in patients with more severe disease, but with substantial heterogeneity [1]. Moreover, blood liver tests’ abnormalities were frequently thought to be of doubtful clinical value.

Most studies have described blood liver tests in a single time point, usually at inclusion [2, 3]. Therefore, we used our case series of the first 20 consecutive patients with COVID-19 admitted to the intensive care unit (ICU) at Curry Cabral Hospital in Lisbon, Portugal, from March 10, 2020, onwards, to describe the temporal evolution of blood liver tests.

Median (interquartile range (IQR)) age was 67 (52–74) years with 18 (90%) males (Table 1). Median (IQR) time from symptom onset to hospital admission was 7.5 (5.5–8.5) days, and median time from hospital admission to ICU admission was 1.1 (0.7–2.1) days. All patients required invasive mechanical ventilation on ICU admission. Median (IQR) sequential organ failure assessment (SOFA) score on ICU admission and peak was 8 (7–9) and 9 (8–11), respectively. As of April 10, following a median (IQR) of 21.5 (11.2–25.4) days post ICU admission, 3 (15%) patients died of multi-organ failure, 14 (70%) were discharged to the ward, and 3 (15%) remained in the ICU.

Table 1.

Baseline characteristics and outcomes of patients

Characteristic Median (IQR) or n (%)
Age (years) 67 (52–74)
Sex (male) 18 (90%)
BMI (kg/m2) 29 (26–32)
Parameters on ICU admission
 PaO2/FiO2 138 (128–163)
 Lactate (mmol/L) 1.1 (0.8–1.2)
 Creatinine (mg/dL) 1.11 (1.04–1.26)
Organ support during ICU stay
 Invasive mechanical ventilation 20 (100%)
 Vasopressors 19 (95%)
 Renal replacement therapy 7 (35%)
SOFA score
 ICU admission 8 (7–9)
 Peak 9 (8–11)
 ICU discharge 3 (2–6)
APACHEII score 18 (14–21)
ICU mortality 3 (15%)
Hospital mortality 3 (15%)
ICU length of stay (days) 10.3 (8.0–12.3)
Hospital length of stay (days) 22.4 (14.1–26.7)

IQR interquartile range, BMI body mass index, PaO2/FiO2 oxygen partial pressure/oxygen inspired fraction, SOFA Sequential Organ Failure Assessment, ICU intensive care unit, APACHEII Acute Physiology and Chronic Health Evaluation II

No patient had documented liver disease prior to hospitalization. During the first 10 days post ICU admission, all patients had at least one abnormal blood liver test. Overtime, only median gamma-glutamiltranspeptidase (GGT), alanine transferase (ALT), and aspartate transferase (AST) showed any increase from upper limit of normal (ULN) and only median GGT had a ≥ 3 fold increase from ULN (Table 2). Median peak GGT was on day 8 post ICU admission. Patients with peak C-reactive protein ≥ 250 mg/L (day 4 post ICU admission) had higher but non-significant median peak GGT (298 vs. 125 IU/L), ALT (101 vs. 42 IU/L), or AST (72 vs. 57 IU/L) than others (P > 0.50 for all comparisons).

Table 2.

Temporal evolution of median levels of blood tests

Test (upper limit of normal) H adm ICU adm D2 D3 D4 D5 D6 D7 D8 D9 D10
INR (≤ 1.2) 1.18 1.17 1.20 1.16 1.17 1.18 1.17 1.15 1.17 1.17 1.16
Bilirubin (≤ 1.2 mg/dL) 0.65 0.80 1.01 1.16 0.80 0.86 1.05 0.92 1.15 0.87 0.97
ALP (≤ 150 IU/L) 61 59 61 74 83 89 101 95 116 125 111
GGT (≤ 64 IU/L) 55 52 53 66 92 73 102 214 237 211 225
ALT (≤ 55 IU/L) 31 30 33 31 43 48 56 67 82 55 72
AST (≤ 34 IU/L) 51 51 51 44 49 57 69 62 60 53 46
CRP (≤ 5 mg/L) 176 207 239 257 271 258 198 153 97 76 74

H adm hospital admission, ICU adm intensive care unit admission, INR international normalized ratio, ALP alkaline phosphatase, GGT gamma-glutamiltranspeptidase, ALT alanine aminotransferase, AST aspartate aminotransferase, CRP C-reactive protein

In our case series, liver injury was frequent but generally transient and non-severe. While synthetic function was largely preserved, late cholestasis was frequently observed. Cholestasis may have been associated to the critical illness itself (inflammation), parenteral nutrition (only 2 patients required parenteral nutrition), or drug toxicity (all patients were on antibiotics, for example ceftriaxone, amoxicillin-clavulanate, or azithromycin) [4, 5]. While cholestasis could have been multifactorial, the differential diagnosis was not easy to perform with precision. Overall, attention to modifiable factors, such as control of inflammation, timing of parenteral nutrition, and avoiding drugs with worse liver toxicity profile, may be important to prevent cholestasis progression in these patients. Further studies are needed to understand liver injury in critically ill patients with COVID-19, especially if there is any direct viral effect on the liver cells.

Acknowledgements

Not applicable.

Abbreviations

ALT

Alanine transferase

ALP

Alkaline phosphatase

AST

Aspartate transferase

COVID-19

2019 coronavirus disease

CRP

C-reactive protein

ICU

Intensive care unit

IMV

Invasive mechanical ventilation

INR

International normalized ratio

IQR

Interquartile range

GGT

Gamma-glutamiltranspeptidase

Authors’ contributions

FSC collected, analyzed, and interpreted the data. FSC drafted the manuscript. The authors read and approved the final manuscript.

Funding

The authors declare that they have no funding source.

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available due to confidentiality but are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

The ethics committee at Curry Cabral Hospital, Lisbon, Portugal, waived the need for consent because the study was observational.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Footnotes

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Filipe S. Cardoso, Email: filipe_sousacardoso@hotmail.com

Rui Pereira, Email: rui.pereira@mail.com.

Nuno Germano, Email: nuno.m.germano@gmail.com.

References

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The datasets generated and/or analyzed during the current study are not publicly available due to confidentiality but are available from the corresponding author on reasonable request.


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