Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19

Table 1 Baseline characteristics of the total population and according to metabolic associated fatty liver disease presence

Characteristics	All, n = 457	No MAFLD, n = 253	MAFLD, n = 204	P value
Demographic features
Sex as male/female, %	65.2/34.8	63.6/36.4	67.2/32.8	0.432
Age in yr	50.4 ± 13.3	52.4 ± 14.0	47.8 ± 11.8	< 0.0001
BMI in kg/m2	30.1 ± 5.6	28.7 ± 4.9	31.8 ± 5.8	< 0.0001
Comorbidities, n (%)
Malnutrition	10 (2.8)	7 (3.4)	3 (1.9)	< 0.0001
Normal weight	49 (13.6)	43 (21.0)	6 (3.9)
Overweight	136 (37.9)	82 (40.0)	54 (35.1)
Obesity G1	110 (30.6)	51 (24.9)	59 (38.3)
Obesity G2	36 (10.0)	16 (7.8)	20 (13.0)
Obesity G3	18 (5.0)	6 (2.9)	12 (7.8)
T2DM	107 (23.5)	47 (18.7)	60 (29.6)	0.006
Hypertension	122 (26.8)	60 (23.8)	62 (30.5)	0.107
Chronic kidney disease	8 (1.8)	6 (2.4)	2 (1.0)	0.225
Pulmonary obstructive disease	4 (0.9)	1 (0.4)	3 (1.5)	0.235
Autoimmune disease	6 (1.3)	3 (1.2)	3 (1.5)	0.551
Immunosuppression	3 (0.7)	3 (1.2)	0 (0)	0.169
Metabolic syndrome	155 (36.0)	61 (25.5)	94 (49.0)	< 0.0001
Prognostic scores
qSOFA	1 (0-1)	1 (0-1)	1 (0-1)	0.800
SOFA	2 (1-2)	2 (1-2)	2 (1-2)	0.034
NEWS	6.7 ± 2.3	6.6 ± 2.3	6.8 ± 2.2	0.190
PSI/PORT	62 (50-80)	62 (50-82)	61 (49-77)	0.316
SMART COP	3 (2-4)	3 (2-4)	3 (2-4)	0.091
Biochemical values
CRP, ref: 0-1 mg/dL	13.2 (6.6-20.7)	13.1 (6.6-20.0)	13.7 (6.2-21.5)	0.286
Ferritin, ref: 11.0-306.8 ng/mL	747.8 ± 665.0	717.2 ± 662.0	784.0 ± 668.0	0.290
D-dimer, ref: 0-500 ng/mL	707 (426-1146)	699 (413-1138)	721 (451-1182)	0.418
LDH, ref: 120-246 U/L	388 ± 160	374 ± 149	406 ± 173	0.032
Troponin, ref: < 15 pg/mL	4.7 (3.2-8.2)	4.7 (3.1-10.4)	4.6 (3.2-7.1)	0.525
CPK, ref: 30-233 U/L	110 (59-242)	98 (55-210)	133 (66-311)	0.006
Bilirubin, ref: 0/3-1 mg/dL	0.68 ± 0.49	0.66 ± 0.54	0.69 ± 0.43	0.593
ALT, ref: 7-52 U/L	37.5 (25.0-56.0)	33.0 (23.8-54.7)	41.0 (28.0-59.0)	0.004
AST, ref: 13-39 U/L	42.0 (30.0-62.0)	40.0 (29.0-58.0)	43.9 (32.9-64.3)	0.051
Globulins, ref: 1.9-3.7 g/dL	3.2 ± 0.4	3.2 ± 0.4	3.2 ± 0.4	0.560
Albumin, ref: 3.5-5.7 g/dL	3.7 ± 0.4	3.6 ± 0.4	3.7 ± 0.4	0.051
ALP, ref: 34-104 U/L	86 (70-111)	86 (70-113)	85 (69-109)	0.505
Creatinine, ref: 0.6-1.2 mg/dL	0.9 (0.8-1.1)	0.9 (0.8-1.1)	0.9 (0.7-1.1)	0.877
Glucose, ref: 70-99 mg/dL	116 (102-144)	110 (99-131)	124 (105-184)	< 0.0001
Leukocytes, ref: 4-12 × 103/μL	7.6 (5.6-10.0)	7.2 (5.4-9.8)	7.9 (5.7-10.3)	0.191
Lymphocytes, ref: 1-3.9 × 103/μL	881.6 ± 509.0	835.0 ± 352.0	938.0 ± 649.0	0.043
Platelets, ref: 150-450 K/μL	239 ± 88	248 ± 95	227 ± 78	0.012
25 (HO) vitamin D, ref: 30-100 ng/mL	21.5 ± 8.0	21.6 ± 8.1	21.5 ± 8.0	0.917
Triglycerides, ref: < 150 mg/dL	159 ± 85	155 ± 60	165 ± 110	0.264
CT scan results, pulmonary involvement
Mild, < 20%	91 (20.0)	51 (20.3)	40 (19.6)	0.281
Moderate, 20%-50%	172 (37.8)	102 (40.6)	70 (34.3)
Severe, > 50%	192 (42.2)	98 (39.0)	94 (46.1)
Treatment, n (%)
Antibiotics	402 (88.4)	228 (90.8)	174 (85.3)	0.096
Antimalarials	132 (28.9)	72 (28.5)	60 (29.4)	0.823
Tocilizumab	51 (11.2)	26 (10.3)	25 (12.3)	0.504
Remdesivir	9 (2.0)	7 (2.8)	2 (1.0)	0.152
PaO2/FiO2 ratio	233.9 ± 109.9	239.0 ± 91.0	227.0 ± 130.0	0.011
Neutrophil/lymphocyte ratio	7.0 (4.4-11.6)	7.2 (4.5-12.0)	6.7 (4.0-10.8)	0.860
Days between the beginning of symptoms and hospitalization	8.2 ± 4.4	8.6 ± 4.6	7.8 ± 4.0	0.110

BMI: Body mass index; T2DM: Type 2 diabetes mellitus; q-SOFA: Quick sequential organ failure assessment; SOFA: Sequential organ failure assessment; NEWS: National early warning score; PSI/PORT: Pneumonia severity index; CRP: C-reactive protein; LDH: Lactate dehydrogenase; CPK: Creatine phosphokinase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; CT: Computed tomography; MAFLD: Metabolic associated fatty liver disease; PaO2/FiO2 ratio: Ratio of arterial oxygen partial pressure to fractional inspired oxygen.

Table 2 Diagnostic yield of the LFN-COVID-19 index in patients with metabolic associated fatty liver disease

Diagnostic yield
Sensitivity	0.787 (0.643-0.893)
Specificity	0.638 (0.563-0.709)
Positive predictive value, %	0.360 (0.273-0.468)
Negative predictive value, %	0.910 (0.855-0.960)
+ Likelihood ratio	2.18 (1.70-2.80)
- Likelihood ratio	0.33 (0.20-0.60)
AUROC	0.770 (0.709-0.823), P < 0.0001
Youden index	0.4257

AUROC: Area under the receiver operating characteristic.

Table 3 Characteristics and outcomes in patients with metabolic associated fatty liver disease according to the LFN-COVID-19 index

	< 1.67, n = 115	> 1.67, n = 89	P value
Demographic features
Sex as male/female, %	63.5/36.5	71.9/28.1	0.203
Age in yr	46 ± 10	50 ± 12	0.011
BMI in kg/m2	31.1 ± 4.8	32.5 ± 6.9	0.111
Prognostic scores
qSOFA	1 (0-1)	1 (1-1)	0.007
SOFA	2 (1-2)	2 (2-3)	0.004
NEWS	7 (5-8)	7 (6-9)	0.035
PSI/PORT	56 (47-69)	66 (53-85)	< 0.0001
SMART COP	3 (2-4)	4 (3-4)	0.012
Biochemical values
CRP, ref: 0-1 mg/dL	8.5 (4.2-18.1)	17.2 (11.6-23.8)	< 0.0001
Ferritin, ref: 11.0-306.8 ng/mL	503 (266-970)	795 (412-1114)	0.003
D-dimer, ref: 0-500 ng/mL	587 (399-962)	967 (606-1549)	< 0.0001
LDH, ref: 120-246 μ/L	312 ± 86	529 ± 180	< 0.0001
Troponin, ref: < 15 pg/mL	3.7 (2.9-5.7)	6.1 (3.8-10.9)	< 0.0001
CPK, ref: 30-223 μ/L	107 (58-222)	190 (78-414)	0.001
Bilirubin, ref: 0/3-1 mg/dL	0.62 ± 0.30	0.78 ± 0.54	0.017
ALT, ref: 7-52 U/L	43.2 (31.0-61.2)	37.0 (26.3-52.8)	0.026
AST, ref: 13-39 U/L	38.3 (27.8-52.2)	52.4 (42.0-73.7)	< 0.0001
Globulins, ref: 1.9-3.7 g/dL	3.22 ± 0.39	3.29 ± 0.43	0.259
Albumin, ref: 3.5-5.7 g/dL	3.90 ± 0.42	3.50 ± 0.40	< 0.0001
ALP, ref: 34-104 μ/L	85 (70-109)	85 (67-110.5)	0.786
Creatinine, ref: 0.6-1.2 mg/dL	0.85 (0.69-1.00)	0.95 (0.79-1.16)	0.005
Glucose, ref: 70-99 mg/dL	118 (102-180)	135 (114-187)	0.03
Leukocytes, ref: 4-12 × 103/μL	7.6 (5.6-9.9)	8.3 (6.3-10.8)	0.089
Lymphocytes, ref: 1-3.9 × 103/μL	937 (693-1210)	715 (510-967)	< 0.0001
Platelets, ref: 150-450 K/μL	228 ± 78	226 ± 79	0.827
25 (HO) vitamin D, ref: 30-100 ng/mL	21.9 ± 7.8	20.9 ± 8.3	0.488
Triglycerides, ref: < 150 mg/dL	151 (118-187)	137 (111-184)	0.13
PaO2/FiO2 ratio	240 (161-287)	159 (96-245)	< 0.0001
Neutrophil/lymphocyte ratio	5.9 (3.5-9.9)	9.6 (6.4-13.7)	< 0.0001
Other, n (%)
Metabolic syndrome	49.0 (46.2)	45.0 (52.3)	0.401
Severe COVID-19, PaO2/FiO2 < 100 mmHg	9 (8.2)	23 (26.7)	< 0.0001
Orotracheal intubation	13 (11.3)	36 (40.9)	< 0.0001
Acute kidney injury	11 (11)	26 (34.7)	< 0.0001
Thrombotic event	1 (1.0)	2 (2.7)	0.576
Death	6 (5.3)	25 (29.8)	< 0.0001
Days between the beginning of symptoms and hospitalization	7.2 ± 3.4	8.6 ± 4.9	0.027
Length of hospital stay in days	7 (4-10)	8 (6-10)	0.131
Days in ICU	7 (5-12)	12 (6-13)	0.395
Days between ICU requirement and death	7 (6-7)	5 (3-7)	0.203

BMI: Body mass index; q-SOFA: Quick-sequential organ failure assessment; SOFA: Sequential organ failure assessment; NEWS: National early warning score; PSI/PORT: Pneumonia severity index; CRP: C-reactive protein; LDH: Lactate dehydrogenase; CPK: Creatine phosphokinase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; COVID-19: Coronavirus disease 2019; ICU: Intensive care unit; PaO2/FiO2 ratio: Ratio of arterial oxygen partial pressure to fractional inspired oxygen.

Table 4 Logistic regression analysis to evaluate the association between LFN-COVID-19 index and clinical outcomes

Orotracheal intubation					Acute kidney injury
	OR	95%CI	B coefficient	P value	OR	95%CI	B coefficient	P value
LFN-COVID-19 index	1.900	1.481-2.437	0.642	0.000	1.849	1.366-2.504	0.615	0.000
Sex	0.605	0.288-1.271	-0.502	0.185	0.280	0.103-0.765	-1.272	0.013
Age	0.966	0.939-0.993	-0.035	0.015	1.021	0.988-1.054	0.021	0.209
BMI	1.054	0.997-1.114	0.053	0.061	1.085	1.011-1.164	0.081	0.023

OR: Odds ratio; CI: Confidence interval; BMI: Body mass index; COVID-19: Coronavirus disease 2019.

Table 5 Cox proportional hazard multivariate analysis for mortality in patients with metabolic associated fatty liver disease according to the LFN-COVID-19 index

	OR	B coefficient	P value	95%CI
LFN-COVID-19 index	0.241	-1.422	0.013	0.079-0.741
PaO2/FiO2 ratio	1.000	0.000	0.877	0.996-1.004
Neutrophil/lymphocyte ratio	1.043	0.042	0.030	1.004-1.083
Creatine phosphokinase	1.001	0.001	0.340	0.999-1.002
Body mass index in kg/m2	1.093	0.089	0.002	1.033-1.157

OR: Odds ratio; CI: Confidence interval; COVID-19: Coronavirus disease 2019; PaO2/FiO2 ratio: Ratio of arterial oxygen partial pressure to fractional inspired oxygen.