Skip to main content
main-content

05.05.2020 | COVID-19 | Research Letter | Ausgabe 1/2020 Open Access

Critical Care 1/2020

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

Zeitschrift:
Critical Care > Ausgabe 1/2020
Autoren:
Filipe S. Cardoso, Rui Pereira, Nuno Germano
Wichtige Hinweise

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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
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/m 2)
29 (26–32)
Parameters on ICU admission
 P aO 2/FiO 2
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, P a O 2 /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.

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.
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​. The Creative Commons Public Domain Dedication waiver ( http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher’s Note

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

Weitere Artikel der Ausgabe 1/2020

Critical Care 1/2020 Zur Ausgabe

Coronavirus Corona-Update

Die aktuelle Entwicklung im Überblick: Nachrichten, Webinare, Übersichtsarbeiten.

Bildnachweise