COVID-19 and liver dysfunction in children: Current views and new hypotheses

Table 1 Laboratory features of coronavirus disease 2019-related liver injury in children

Ref.	Number of patients	Age range	Abnormal liver function	E-ALT	E-AST	E-ALP	E-GGT	E-TBIL	D-albumi, n (%)
Alkan et al[19]	294	14 d-18 years	130 (44.2%)	15 (5.1%)	98 (33.3%)	19 (6.6%)	26 (8.9%)	11 (3.8%)	NA
Esmaeili et al[20]	18	3-10 years	6 (33.3%)	5 (27.8%)	7 (38.9%)	0	NA	3 (16.7%)	3 (16.7%)
Liu et al[21]	46	0-1 year	20 (43.5%)	11 (25.0%)	20 (45.5%)	NA	NA	6 (13.6%)	8 (18.2%)
Parri et al[22]	130	0-17 years	NA	8/68 (11.8%)	11/60 (18.3%)	NA	NA	NA	NA
Du et al[23]	182	0-15 years	NA	9/180 (5.0%)	24/180 (13.3%)	11/174 (6.3%)	NA	NA	NA
Sun et al[24]	8	2 mo-15 years	4 (50.0%)	4 (50.0%)	0	NA	NA	0	NA

E-ALT: Elevated alanine aminotransferase; E-AST: Elevated aspartate aminotransferase; E-ALP: Elevated alkaline phosphatase; E-GGT: Elevated gamma-glutamyl transferase; E-TBIL: Elevated total bilirubin; D-albumin: Decreased albumin; NA: Not available.

Table 2 The frequencies of different coronavirus disease 2019-related liver injury types in adults and children

CRLI types	Liver test parameters[18]	Adults[18]	Children[19]
Hepatocyte type	ALT/AST ≥ 3×ULN	66 (20.8%)	24 (18.5%)
Cholangiocyte type	ALP/GGT ≥ 2×ULN	93 (29.2%)	93 (71.5%)
Mixed type	ALT/AST ≥ 3×ULN and ALP/GGT ≥ 2×ULN	138 (43.4%)	13 (10.0%)

CRLI: Coronavirus disease 2019-related liver injury; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; ULN: Upper limit of normal.

Table 3 Immune features in pediatric patients with varying degrees of coronavirus disease 2019

Biomarker	Severe	Moderate	Mild/asymptomatic
T lymphocyte[45-47]	CD3+↓; CD4+ ↓; CD8+ ↓; CD3+CD4+ ↓; CD3+CD8+ ↓	CD3+ →; CD4+ →/↑; CD8+ →	CD3+ →; CD4+ →; CD8+ →
B lymphocyte[23,46]	↓	→/↑	→/↑
Innate cell[23,46]	Monocytes ↑; Neutrophils ↑; NK cells ↓	Monocytes ↑; NK cells ↑; Neutrophils ↓	Monocytes →; Neutrophils →; NK cells →
Immunological parameters[23,46]	IgE ↑; IgG ↓; IgA ↑; IgM ↓; C3 ↑/↓; C4 ↑/↓	IgE →/↑; IgG →/↑; IgA →/↑; IgM →; C3 ↑/↓; C4 ↑	IgE →/↑; IgG →/↑; IgA →/↑; IgM →; C3 ↑/↓; C4 →
Inflammatory cytokine[23,46,47]	IL-2 ↑; IL-4 ↑; IL-6 ↑; IL-10 ↑; IFN-γ ↑; TNF-α ↑	IL-2 →; IL-4 →; IL-6 →; IL-10 ↑; IFN-γ →; TNF-α →	IL-2 →; IL-4 →; IL-6 →; IL-10 →; IFN-γ →; TNF-α →
Chemokines[49]	CXCL10 →; CXCL8 →; CCL2 →	CXCL10 →; CXCL8 →; CCL2 →	CXCL10 →; CXCL8 →; CCL2 →

↑: Increased; ↓: Decreased; →: Unchanged.

NK: Nature killer; Ig: Immunoglobulin; C: Complement; IL: Interleukin; IFN: Interferon; TNF: Tumor necrosis factor; CXCL: Chemokine (C-X-C motif) ligand; CCL: CC chemokine ligand.