Chronic hepatitis-C infection in COVID-19 patients is associated with in-hospital mortality

doi:10.12998/wjcc.v9.i29.8749

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World J Clin Cases. Oct 16, 2021; 9(29): 8749-8762
Published online Oct 16, 2021. doi: 10.12998/wjcc.v9.i29.8749

Table 1 Comparison between patients with and without hepatitis C virus, n (%)

	All patients (n = 1193)			Propensity score matched¹ (n = 98)
	No HCV (n = 1143)	HCV (n = 50)	P value	No HCV (n = 48)	HCV (n = 50)	P value
Age (yr)	62 ± 16	64 ± 9	0.402	64 ± 15	64 ± 9	0.803
Gender (female)	456 (39.90)	14 (28.00)	0.092	20 (41.67)	14 (28.00)	0.155
Body mass index (kg/m²)	30 ± 7	27.7 ± 8.5	0.026	27.9 ± 6.8	28 ± 9	0.917
Hypertension	703 (61.50)	31 (62.00)	0.944	33 (68.75)	31 (62.00)	0.483
Diabetes mellitus)	530 (46.37)	17 (34.00)	0.086	17 (35.42)	17 (34.00)	0.883
Human immune-deficiency virus	58 (05.07)	21 (42.00)	< 0.001	17 (35.42)	21 (42.00)	0.504
Asthma	144 (12.60)	10 (20.00)	< 0.001	9 (18.75)	10 (20.00)	0.612
Chronic obstructive pulmonary disease	105 (09.19)	14 (28.00)	< 0.001	9 (18.75)	14 (28.00)	0.280
Hepatitis B infection	1 (00.09)	3 (06.00)	< 0.001	0 (00.00)	3 (06.00)	0.085
Congestive heart failure	105 (09.19)	12 (24.00)	0.001	10 (20.83)	12 (24.00)	0.707
Coronary artery disease	119 (10.41)	6 (12.00)	0.720	6 (12.50)	6 (12.00)	0.940
Chronic kidney disease	89 (07.79)	9 (18.00)	0.01	5 (10.42)	9 (18.00)	0.284
End stage renal disease	77 (06.74)	5 (10.00)	0.372	2 (04.17)	5 (10.00)	0.262
Fever	753 (65.88)	31 (62.00)	0.525	26 (54.17)	31 (62.00)	0.585
Cough	771 (67.45)	24 (48.00)	0.003	27 (56.25)	24 (48.00)	0.294
Shortness of breath	787 (68.85)	40 (80.00)	0.110	34 (70.83)	40 (80.00)	0.478
Myalgia	352 (30.80)	11 (22.00)	0.175	19 (39.58)	11 (22.00)	0.04
Chest discomfort	144 (12.60)	5 (10.00)	0.572	3 (06.25)	5 (10.00)	0.538
Atypical symptoms	392 (34.30)	19 (38.00)	0.611	20 (41.67)	19 (38.00)	0.585
Symptom onset to hospitalization (d)	5.85 ± 5.56	3.79 ± 4.04	0.034	6.2 ± 5.7	3.8 ± 4.04	0.053
Length of hospital stay (d)	8.05 ± 7.05	6.2 ± 4.3	0.072	7 ± 5.79802	6.2 ± 4.3	0.454
Hemoglobin	13.0 ± 2.2	12.2 ± 2.7	0.021	12.5 ± 2.1	12.2 ± 2.7	0.598
Total white count	8.6 ± 6.6	9.8 ± 13.1	0.244	7.78 ± 3.5	9.8 ± 13.1	0.300
Platelets	221.7 ± 103.3	183 ± 73.5	0.015	234.4 ± 100	183 ± 73	0.007
Neutrophilic count	6.8 ± 4.05	6.1 ± 3.8	0.224	6.3 ± 3.4	6.1 ± 3.8	0.780
Lymphocyte count	1.18 ± 4.86	2.86 ± 12.3	0.037	0.99 ± 0.52	2.86 ± 12.3	0.302
D-dimer	3115 ± 9997	2270 ± 5383	0.582	6883 ± 28017	2270 ± 5383	0.293
Lactate dehydrogenase	581 ± 393	623 ± 391	0.477	523 ± 419	623 ± 391	0.248
High sensitivity C-reactive protein	143 ± 113	98 ± 76	0.013	129 ± 89	98 ± 75	0.095
Ferritin	1148 ± 1574	1265 ± 2098	0.647	1053 ± 1267	1265 ± 2098	0.576
Lactate	2.3 ± 1.9	2.7 ± 2.6	0.265	2.07 ± 1.3	2.7 ± 2.6	0.189
Prothrombin time (s)	14 ± 10.7	13.4 ± 2.5	0.716	13.6 ± 2.3	13.4 ± 2.4	0.700
Activated partial thromboplastin time (s)	32.2 ± 7.9	32.7 ± 6.3	0.67	31.4 ± 5.4	32.7 ± 6.3	0.317
Creatinine	1.9 ± 2.6	3.3 ± 3.5	< 0.001	2.01 ± 2.4	3.3 ± 3.5	0.039
Alanine transaminase	43.7 ± 66.4	53.2 ± 121.7	0.386	40.8 ± 37.5	53.2 ± 121.7	0.538
Aspartate transaminase	68.6 ± 90.8	128.1 ± 367.2	0.001	59.8 ± 43.5	128.2 ± 367	0.246
Alkalaine phosphatase	94.2 ± 86.4	111.5 ± 143	0.224	82.3 ± 40.7	111.5 ± 143	0.217
Total bilirubin	0.6 ± 0.7	0.8 ± 0.86	0.111	0.54 ± 0.41	0.8 ± 0.9	0.087
Combined bilirubin	0.27 ± 0.45	0.45 ± 0.68	0.02	0.26 ± 0.28	0.45 ± 0.68	0.115
Total protein	6.98 ± 0.83	7.2 ± 0.98	0.163	6.91 ± 0.72	7.2 ± 0.98	0.175
Albumin	3.59 ± 0.55	3.44 ± 0.56	0.089	3.6 ± 0.5	3.4 ± 0.6	0.209
Procalcitonin	2.34 ± 9.4	7.27 ± 21.4	0.02	3.08 ± 8.8	7.3 ± 21.4	0.453
Hydroxychloroquine	878 (76.82)	36 (72.00)	0.711	33 (68.75)	36 (72.00)	0.725
Azithromycin	839 (73.40)	32 (64.00)	0.303	35 (72.92)	32 (64.00)	0.343
Tocilizumab	78 (06.82)	0 (00.00)	0.149	4 (08.33)	0 (00.00)	0.054
Mechanical ventilation	449 (39.28)	29 (58.00)	0.003	4 (08.33)	29 (58.00)	< 0.001
Death	386 (33.77)	28 (56.00)	0.004	7 (14.58)	28 (56.00)	< 0.001

¹Patients without hepatitis C virus (HCV) were matched to patients with HCV using propensity score matching for age, sex, body mass index, and all risk factors. HCV: Hepatitis C virus.

Table 2 Cox regression model for all patients and hepatitis C virus patients for prediction of mortality

	All patients (n = 1193)				Propensity score matched (n = 98)
	Univariate		Multivariate		Univariate		Multivariate
	Exp (B)	Sig.	Exp (B)	Sig.	Exp (B)	Sig.	Exp (B)	Sig.
Age (yr)	1.028	< 0.001	1.029	< 0.001	1.022	0.183	-	-
Gender (female)	0.675	< 0.001	0.865	0.42	0.488	0.05	0.714	0.110
Body mass index (kg/m²)	0.991	0.184	-	-	1.014	0.514	-	-
Hypertension	1.611	< 0.001	0.843	0.386	2.87	0.004	2	0.051
Diabetes mellitus	1.394	0.001	1.208	0.277	1.06	0.864	-	-
Human immune-deficiency virus	1.797	< 0.001	1.251	0.492	1.92	0.064	-	-
Asthma	0.864	0.341	-	-	1.39	0.357	-	-
Chronic obstructive pulmonary disease	1.435	0.013	1.043	0.879	1.222	0.591	-	-
Hepatitis B infection	1.984	0.237	-	-	1.04	0.962	-	-
HCV	2.224	< 0.001	2.435	0.041	3.88	0.001	3.46	0.004
Congestive heart failure	1.4	0.02	1.249	0.356	1.253	0.545	-	-
Coronary artery disease	1.387	0.023	1.092	0.734	1.05	0.923	-	-
End stage renal disease	1.208	0.305	-	-	1.013	0.983	-	-
Chronic kidney disease	1.437	0.016	1.188	0.535	1.024	0.957	-	-
Hemoglobin	0.966	0.123	-	-	0.925	0.337	-	-
Total white count	1.006	0.376	-	-	1.004	0.736	-	-
Platelets	0.998	< 0.001	0.999	0.438	0.999	0.525	-	-
Neutrophilic count	1.023	0.028	0.991	0.658	1.072	0.145	-	-
Lymphocyte count	0.993	0.641	1	0.163	1.000	0.976	-	-
D-dimer	1	< 0.001	1.001	< 0.001	1.000	0.09	-	-
Lactate dehydrogenase	1.001	< 0.001	1.001	0.374	1.000	0.714	-	-
High sensitivity C-reactive protein	1.002	< 0.001	1	0.553	0.999	0.788	-	-
Ferritin	1	0.002	1.053	0.028	1.000	0.902	-	-
Prothrombin time (s)	1.001	0.89	-	-	1.1	0.281	-	-
Activated partial thromboplastin time (s)	0.998	0.804	-	-	0.966	0.281	-	-
Creatinine	1.072	< 0.001	-	-	1.08	0.91	-	-
Alanine transaminase	0.999	0.325	-	-	0.998	0.371	-	-
Aspartate transaminase	1	0.391	-	-	0.999	0.402	-	-
Alkalaine phosphatase	0.999	0.222	-	-	0.275	0.995	-	-
Total bilirubin	1.131	0.002	1.026	0.925	1.16	0.475	-	-
Combined bilirubin	1.327	< 0.001	1.091	0.733	1.17	0.510	-	-
Total protein	0.932	0.235	-	-	0.892	0.560	-	-
Albumin	0.681	< 0.001	0.933	0.678	0.613	0.114	-	-
Procalcitonin	1.014	< 0.001	1.001	0.793	1.008	0.544	-	-

HCV: Hepatitis C virus.

Table 3 Comparison between liver enzymes, acute liver injury, chronic liver disease, and fibrosis score between patients with and without hepatitis C virus, n (%)

	All (n = 1065)	ALI patients (n = 1065)			Propensity score matched (n = 81)
	All (n = 1065)	No HCV (n = 1014)	HCV (n = 41)	P value	No HCV (n = 40)	HCV (n = 41)	P value
AST/ALT	1.88 ± 1.5	1.86 ± 1.5	2.4 ± 1.3	0.023	1.8 ± 0.88	2.4 ± 1.27	0.015
Any liver enzyme elevated	639 (60)	610 (60)	29 (71)	0.174	25 (63)	29 (71)	0.423
Normal liver enzymes	416 (39)	311 (31)	10 (24)	0.242	15 (38)	10 (24)	0.223
Only ALT elevated	6 (1)	6 (1)	0 (0)		0 (0)	0 (0)
Only AST elevated	432 (41)	409 (40)	23 (56)		15 (38)	2356
Both elevated	201 (19)	195 (19)	6 (15)		10 (25)	6 (15)
AST > ALT	423 (40)	399 (39)	20 (49)	0.394			0.394
All AST > ALT	633 (59)	604 (60)	29 (71)	0.153	25 (63)	29 (71)	0.423
Fatty liver	50 (5)	48 (5)	2 (5)	0.931	1 (3)	2 (5)	0.582
History of cirrhosis	6 (1)	5 (1)	1 (2)	0.228	2 (5)	1 ()	0.534
Fib-4 score	3.43 ± 5.5	3.47 ± 5.6	3.1 ± 3.6	0.642	3.4 ± 2.25	3.1 ± 3.6	0.249
ALI¹	107 (10)	100 (10)	7 (17)	0.128	3 (8)	7 (17)	0.166

¹Acute liver injury; defined as any of the following criteria: Both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevated 2 times above the upper normal; and Limit or any of AST or ALT elevated 2 times above the upper normal level, and at least one of the following: Elevated combined bilirubin, total bilirubin or elevated PT more than 2 times the normal limit. HCV: Hepatitis C virus; ALI: Acute liver injury AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 4 Comparison between Liver enzymes, acute liver injury, and fibrosis score between patients with and without hepatitis C virus for prediction of mortality, n (%)

	ALl patients (n = 1065)				Propensity score matched (n = 81)
	Univariate		Multivariate		Univariate		Multivariate
	Exp (B)	Sig.	Exp (B)	Exp (B)	Sig.	Exp (B)	Sig.	Sig.
AST/ALT	1.1	< 0.001	1.06	< 0.001	1.204	0.221	-	-
Any liver enzyme elevated	1.427	0.002	0.001	0.823	1.204	0.624	-	-
All AST > ALT	1.455	0.001	0.001	0.852	1.204	0.624	-	-
History of cirrhosis	1.368	0.659	-	-	1.95	0.513	-	-
ALI¹	1.418	0.015	1.045	0.792	1.132	0.817	-	-
Fib-4 score	1.02	< 0.001	1.022	< 0.001	1.1	0.042	1.1	0.08
HCV	2.224	< 0.001	2.15	< 0.001	3.88	0.001	3.75	0.002

Table 5 Subgroup comparisons and cox-regression predictors of outcomes for a subset composed of patients with chronic hepatitis C virus and propensity score matched patients without hepatitis C virus, n (%)

	Propensity score matched (n = 72)
	Comparison between groups			Cox-regression analysis
	Comparison between groups			Univariate		Multivariate
	NO HCV (n = 48)	HCV with viral load (n = 24)	P value	Exp (B)	Sig.	Exp (B)	Sig.
Age (yr)	64.4 ± 15.1	64.4 ± 9.8	0.995	1.021	0.293	-	-
Gender (female)	28 (58)	17 (71)	0.302	0.481	0.088	-	-
Body mass index (kg/m²)	27.9 ± 6.8	26.0 ± 6.2	0.252	1.014	0.625	-	-
Hypertension	33 (69)	16 (67)	0.858	3.03	0.014	2.55	0.035
Diabetes mellitus	17 (35)	7 (29)	0.596	1.05	0.902	-	-
Human immune-deficiency virus	17 (35)	9 (38)	0.862	1.79	0.185	-	-
Asthma	9 (19)	4 (17)	0.828	1.81	0.251	-	-
Chronic obstructive pulmonary disease	9 (19)	5 (21)	0.833	1.386	0.483	-	-
Hepatitis B infection	1 (0.2)	0 (0)	0.476	1.04	0.976	-	-
HCV	0 (0)	24 (100)	-	3.47	0.007	3.2	0.014
Congestive heart failure	10 (21)	5 (21)	1.000	1.41	0.448	-	-
Coronary artery disease	6 (13)	2 (8)	0.596	1.12	0.845	-	-
End stage renal disease	2 (0.4)	1 (4)	1.000	1.65	0.628	-	-
Chronic kidney disease	5 (10)	6 (25)	0.105	1.1	0.875	-	-
Hemoglobin	12.5 ± 2.1	11.7 ± 2.6	0.166	0.921	0.424	-	-
Total white count	7.8 ± 3.5	12 ± 17.9	0.122	1.006	0.618	-	-
Platelets	234.4 ± 100.3	185 ± 86.2	0.051	1.000	0.978	-	-
Neutrophilic count	6.27 ± 3.4	6.24 ± 4.3	0.981	1.11	0.056	-	-
Lymphocyte count	0.99 ± 0.5	4.62 ± 17.0	0.145	1.002	0.897	-	-
D-dimer	6883 ± 28017	1154 ± 1807	0.333	1.000	0.054	-	-
Lactate dehydrogenase	523 ± 419	649 ± 484	0.273	1.000	0.898	-	-
High sensitivity C-reactive protein	129 ± 90	113 ± 89	0.518	0.999	0.751	-	-
Ferritin	1053 ± 1267	1373 ± 2775	0.533	1.000	0.661	-	-
Prothrombin time (s)	13.6 ± 2.3	13.5 ± 2.5	0.820	1.05	0.636	-	-
Activated partial thromboplastin time (s)	31.4 ± 5.4	32.9 ± 7.28	0.365	0.935	0.138	-	-
Creatinine	2.01 ± 2.4	3.2 ± 4.	0.132	1.06	0.315	-	-
Alanine transaminase	40.8 ± 37.5	62.1 ± 169.8	0.448	0.998	0.427	-	-
Aspartate transaminase	59.8 ± 43.5	169.8 ± 518.6	0.185	0.999	0.433	-	-
Alkaline phosphatase	82.3 ± 40.7	114.5 ± 165.7	0.246	0.996	0.376	-	-
Total bilirubin	0.54 ± 0.4	0.93 ± 1.1	0.05	1.236	0.336	-	-
Combined bilirubin	0.26 ± 0.28	0.58 ± 0.9	0.05	1.223	0.428	-	-
Total protein	6.91 ± 0.72	7.0 ± 0.95	0.618	0.813	0.380	-	-
Albumin	3.6 ± 0.51	3.3 ± 0.52	0.073	0.509	0.079	-	-
Procalcitonin	3.1 ± 8.8	4.6 ± 11.7	0.695	0.984	0.538	-	-
Hydroxychloroquine	33 (69)	18 (75)	0.582	-	-	-	-
Azithromycin	35 (73)	13 (54)	0.112	-	-	-	-
Tocilizumab	4 (8)	0 (0)	0.146	-	-	-	-
Mechanical ventilation	4 (8)	15 (63)	< 0.001	-	-	-	-
Death	7 (15)	15 (63)	< 0.001	-	-	-	-

HCV: Hepatitis C virus.

Citation: Ronderos D, Omar AMS, Abbas H, Makker J, Baiomi A, Sun H, Mantri N, Choi Y, Fortuzi K, Shin D, Patel H, Chilimuri S. Chronic hepatitis-C infection in COVID-19 patients is associated with in-hospital mortality. World J Clin Cases 2021; 9(29): 8749-8762
URL: https://www.wjgnet.com/2307-8960/full/v9/i29/8749.htm
DOI: https://dx.doi.org/10.12998/wjcc.v9.i29.8749