Presentation, patterns and predictive value of baseline liver tests on outcomes in COVID-19 patients without chronic liver disease

Table 1 Baseline characteristics of the study population (n = 10614)

Demographics
Sex
Male	6243 (58.8%)
Female	4371 (41.2%)
Race
White	4037 (38.0%)
Black	2248 (21.2%)
Asian	914 (8.6%)
Other/multiracial	2942 (27.7%)
Unknown	473 (4.5%)
Ethnicity
Non-Hispanic or Latino or other/unknown	8338 (78.6%)
Hispanic or Latino	2276 (21.4%)
Age (yr)	65 (54-77)
Body mass index (kg/m2)1	28.3 (24.9-32.6)
< 30	5120 (61.4%)
≥ 30	3220 (38.6%)
Presence of co-morbid conditions
Hypertension	6204 (58.5%)
Diabetes mellitus	3764 (35.5%)
Coronary artery disease	1328 (12.5%)
Heart failure	832 (7.8%)
Malignancy	791 (7.5%)
Chronic obstructive pulmonary disease	608 (5.7%)
Chronic kidney disease (stage I-IV)	391 (3.7%)
End-stage renal disease	434 (4.1%)
Liver chemistries (within 24 h)
AST (IU/L)1	46 (31-72)
Normal	4377 (41.3%)
> 1 to ≤ 4 × ULN	5713 (53.8%)
> 4 to ≤ 10 × ULN	437 (4.1%)
> 10 × ULN	85 (0.8%)
ALT (IU/L)	33 (21-56)
Normal	4883 (46.0%)
> 1 to ≤ 4 × ULN	5159 (48.6%)
> 4 to ≤ 10 × ULN	484 (4.6%)
> 10 × ULN	88(0.8%)
Alkaline phosphatase (IU/L)1	75 (59-98)
Normal	9242 (87.1%)
> 1 to ≤ 4 × ULN	1333 (12.6%)
> 4 to ≤ 10 × ULN	35(0.3%)
> 10 × ULN	2 (0.02%)
Bilirubin (mg/dL)1	0.5 (0.4-0.7)
Normal	10119 (95.4%)
> 1 to ≤ 4 × ULN	486 (4.6%)
> 4 to ≤ 10 × ULN	5 (0.05%)
> 10 × ULN	3 (0.03%)

¹Missing data for some patients: Body mass index (n = 2274), alkaline phosphatase (n = 2), aspartate aminotransferase (n = 2), and bilirubin (n = 1).

Data summarized as n (%) for categorical variables and median (interquartile range) for continuous variables. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ULN: Upper limit of normal.

Table 2 Correlations between baseline liver chemistry elevations and demographic characteristics of the study population

	Elevated ALP	P value	Elevated AST	P value	Elevated ALT	P value	Elevated Bilirubin	P value
Sex		0.001		< 0.001		0.34		< 0.001
Female	619 (14.2%)		2191 (50.1%)		2336 (53.4%)		124 (2.8%)
Male	751 (12.0%)		4044 (64.8%)		3395 (54.4%)		370 (5.9%)
Race		< 0.001		< 0.001		< 0.001		0.51
Asian	134 (14.7%)		613 (67.1%)		533 (58.3%)		43 (4.7%)
Black	228 (10.1%)		1332 (59.3%)		1146 (51.0%)		117 (5.2%)
Other/multiracial	468 (15.9%)		1845 (62.7%)		1836 (62.4%)		139 (4.7%)
Unknown	74 (15.6%)		300 (63.4%)		304 (64.3%)		17 (3.6%)
White	466 (11.6%)		2145 (53.2%)		1912 (47.4%)		178 (4.4%)
Ethnicity		< 0.001		< 0.001		< 0.001		0.51
Hispanic or Latino	398 (17.5%)		1410 (62.0%)		1450 (63.7%)		97 (4.3%)
Non-Hispanic or Latino	864 (11.3%)		4384 (57.3%)		3852 (50.4%)		361 (4.7%)
Unknown or other	108 (15.7%)		441 (64.0%)		429 (62.3%)		36 (5.2%)
BMI (kg/m2)		< 0.001		0.08		< 0.001		< 0.001
< 30	730 (14.3%)		2996 (58.5%)		2694 (52.6%)		269 (5.3%)
≥ 30	336 (10.5%)		1946 (60.4%)		1885 (58.5%)		111 (3.5%)
Diabetes mellitus		0.03		< 0.001		< 0.001		< 0.001
No	920 (13.4%)		1158 (60.7%)		3897 (56.9%)		356 (5.2%)
Yes	450 (12.0%)		2077 (55.2%)		1834 (48.7%)		138 (3.7%)
Hypertension		< 0.001		< 0.001		< 0.001		0.36
No	642 (14.6%)		2683 (60.9%)		2649 (60.1%)		215 (4.9%)
Yes	728 (11.7%)		3552 (57.3%)		3082 (49.7%)		279 (4.5%)
Coronary artery disease		0.69		0.006		< 0.001		0.09
No	1194 (12.9%)		5501 (59.3%)		5184 (55.8%)		420 (4.5%)
Yes	176 (13.3%)		734 (55.3%)		547 (41.2%)		74 (5.6%)
Congestive heart failure		< 0.001		< 0.001		< 0.001		< 0.001
No	1223 (12.5%)		5811 (59.4%)		5419 (55.4%)		432 (4.4%)
Yes	147 (17.7%)		424 (51.0%)		312 (37.5%)		62 (7.5%)
COPD		0.24		< 0.001		< 0.001		0.46
No	1301 (13.0%)		5939 (59.4%)		5504 (55.0%)		462 (4.6%)
Yes	69 (11.4%)		296 (48.7%)		227 (37.3%)		32 (5.3%)
CKD (stage I-IV)		0.82		0.001		< 0.001		0.59
No	1321 (12.9%)		6036 (59.1%)		5582 (54.6%)		478 (4.7%)
Yes	49 (12.5%)		199 (50.9%)		149 (38.1%)		16 (4.1%)
End-stage renal disease		< 0.001		< 0.001		< 0.001		0.09
No	1265 (12.4%)		6044 (59.4%)		5621 (55.2%)		481 (4.7%)
Yes	105 (24.2%)		191 (44.0%)		110 (25.4%)		13 (3.0%)
Malignancy		0.58		< 0.001		< 0.001		0.049
No	1273 (13.0%)		5827 (59.3%)		5380 (54.8%)		446 (4.5%)
Yes	97 (12.3%)		408 (51.7%)		351 (44.4%)		48 (6.1%)

ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; CKD: Chronic kidney disease; COPD: Chronic obstructive pulmonary disease.

Table 3 Associations between liver chemistries and outcomes

	In-hospital mortality				In-hospital mortality or need for mechanical ventilation
	Unadjusted analysis-HR (95%CI)	P value	Adjusted analysis1-HR (95%CI)	P value	Unadjusted analysis-HR (95%CI)	P value	Adjusted analysis1-HR (95%CI)	P value
AST
Normal	Ref.		Ref.		Ref.		Ref.
> 1 to ≤ 4 × ULN	1.29 (1.17-1.42)	< 0.001	1.65 (1.47-1.85)	< 0.001	1.29 (1.13-1.46)	< 0.001	1.73 (1.47-2.04)	< 0.001
> 4 to ≤ 10 × ULN	1.66 (1.38-1.99)	< 0.001	1.69 (1.33-2.14)	< 0.001	1.67 (1.27-2.20)	< 0.001	2.09 (1.42-3.07)	< 0.001
> 10 × ULN	3.50 (2.56-4.78)	< 0.001	2.64 (1.73-4.04)	< 0.001	3.89 (2.48-6.10)	< 0.001	3.38 (1.78-6.40)	< 0.001
ALT
Normal	Ref.		Ref.		Ref.		Ref.
> 1 to ≤ 4 × ULN	0.84 (0.77-0.91)	< 0.001	1.21 (1.09-1.34)	< 0.001	0.72 (0.63-0.81)	< 0.001	1.20 (1.02-1.40)	0.02
> 4 to ≤ 10 × ULN	0.88 (0.71-1.09)	0.24	1.22 (0.93-1.61)	0.15	0.79 (0.57-1.09)	0.15	1.40 (0.87-2.26)	0.16
> 10 × ULN	1.71 (1.20-2.45)	0.003	1.34 (0.81-2.22)	0.26	1.42 (0.80-2.51)	0.23	1.36 (0.58-3.19)	0.48
Alkaline phosphatase
Normal	Ref.		Ref.		Ref.		Ref.
Elevated	1.27 (1.14-1.43)	< 0.001	1.29 (1.12-1.48)	< 0.001	1.19 (1.01-1.42)	0.04	1.39 (1.12-1.72)	0.003
Bilirubin
Normal	Ref.		Ref.		Ref.		Ref.
Elevated	1.55 (1.32-1.82)	< 0.001	1.12 (0.92-1.37)	0.27	1.69 (1.34-2.13)	< 0.001	0.96 (0.71-1.30)	0.79
AST:ALT ratio
≤ 1	Ref.		Ref.		Ref.		Ref.
> 1	2.08 (1.82-2.37)	< 0.001	1.72 (1.46-2.02)	< 0.001	2.61 (2.13-3.19)	< 0.001	1.84 (1.41-2.40)	< 0.001
Pattern of liver injury2
Normal or non-severe	Ref.		Ref.		Ref.		Ref.
Hepatocellular	0.93 (0.80-1.09)	0.39	0.90 (0.74-1.11)	0.33	0.84 (0.66-1.07)	0.15	1.18 (0.85-1.65)	0.33
Mixed	1.14 (0.74-1.75)	0.56	1.06 (0.65-1.73)	0.82	1.00 (0.52-1.93)	0.99	1.02 (0.44-2.37)	0.96
Cholestatic	1.17 (0.85-1.61)	0.33	1.57 (1.07-2.28)	0.02	1.25 (0.81-1.93)	0.31	2.05 (1.17-3.58)	0.01

¹Adjusted for age (time-varying), sex (time-varying), race (time-varying), ethnicity, and comorbidities (obesity, hypertension, diabetes, coronary artery disease, chronic kidney disease, end-stage renal disease, chronic obstructive pulmonary disease, heart failure, and cancer).

²Defined as: Normal or non-severe [alanine aminotransferase (ALT) ≤ 3 × ULN and alkaline phosphatase ≤ 2 × upper limit of normal (ULN)], hepatocellular (ALT > 3 × ULN and alkaline phosphatase ≤ 2 × ULN), mixed (ALT > 3 × ULN and alkaline phosphatase > 2 × ULN), and cholestatic (ALT ≤ 3 × ULN and alkaline phosphatase > 2 × ULN).

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; CI: Confidence interval; HR: Hazard ratio; ULN: Upper limit of normal.