Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites

Table 1 Baseline characteristics of patients from the polymorphism group and the wild-type group

	Polymorphism group (n = 28)	Wild-type group (n = 230)	P value
Age (yr)	65.93 ± 12.1	64.90 ± 12.7	0.74
Gender (male/female)	17 (60.7)/ 11 (39.3)	128 (55.7)/ 102 (44.3)	0.69
Cause of cirrhosis (%)			0.07
Alcohol	14 (50)	125 (54.3)
Hepatitis C virus	11 (39.3)	82 (35.7)
Hepatitis B virus	0 (0)	8 (3.5)
Alcohol + HCV/HVB	6 (21.4)	18 (7.8)
Others	3 (10.7)	22 (9.6)
Active alcoholism (%)	9/20 (45)	80/143 (55.9)	0.84
Diabetes mellitus (%)	9 (32.1)	75 (32.6)	1.00
Child-Pugh score	8.25 ± 1	8.31 ± 1.6	0.95
MELD score	15.29 ± 4.8	15.35 ± 6.2	0.69
Previous decompensations (%)	20 (71.4)	160 (69.6)	1.00
Previous ascites (%)	19 (67.9)	151 (65.7)	1.00
Previous encephalopathy (%)	13 (46.4)	51 (22.2)	0.009
Previous variceal bleeding (%)	7 (25)	54 (23.5)	0.82
Previous spontaneous bacterial peritonitis (%)	3 (10.7)	16 (7)	0.44
Hepatocellular carcinoma (%)	4 (14.3)	26 (11.3)	0.55
Norfloxacin prophylaxis (%)	4 (14.3)	18 (7.8)	0.28
Beta-blockers (%)	10 (35.7)	74 (32.2)	0.68
Diuretics (%)	15 (53.6)	135 (58.7)	0.69
Serum sodium (mmol/L)	135.14 ± 6.3	135.14 ± 9.8	0.78
Serum urea (mmol/L)	9.6 ± 4.1	9.6 ± 9.1	0.18
Serum creatinine (μmol/L)	117.29 ± 59.6	100.6 ± 59.9	0.01
Serum bilirubin (μmol/L)	54.7 ± 59.7	43 ± 34.1	0.64
Serum albumin (g/L)	26.6 ± 5.5	27.9 ± 5.5	0.43
Prothrombin time ratio	1.51 ± 0.24	1.57 ± 0.67	0.65
Ascitic fluid total protein (g/L)	13.9 ± 6.6	15.6 ± 10.7	0.30
First decompensation1
Ascites (%)	19 (67.8)	165 (71.7)	0.66
Encephalopathy (%)	3 (10.7)	6 (2.6)	0.06
Variceal bleeding (%)	4 (14.3)	44 (19.1)	0.79
Infection (%)	2 (7.1)	12 (5.2)	0.65
Cause of current admission2
Ascites (%)	8 (28.6)	101 (43.9)	0.15
Encephalopathy (%)	5 (17.9)	22 (9.6)	0.18
Variceal bleeding (%)	3 (10.7)	31 (13.5)	1.00
Spontaneous bacterial peritonitis (%)	6 (21.4)	33 (14.3)	0.39
Other infection (%)	3 (10.7)	13 (5.7)	0.39
Other (%)	3 (10.7)	30 (13)	1.00

¹Refers to the first decompensation that patients presented in the past (in patients with previous decompensation) or at present admission (in patients without previous decompensation);

²Main cause of the hospitalization in which the patient was included to the study. Data are presented as mean ± SD or frequencies (%). MELD: Model for end-stage liver disease; HCV: Hepatitis C virus; HBV: Hepatitis B virus.

Table 2 Overall incidence, number of episodes and causative bacteria of infections in patients from the polymorphism group and the wild-type group during follow-up

	Polymorphism group (n = 28)	Wild-type group (n = 230)	P value
Total infections
Patients (%)	22 (78.6)	171 (74.3)	0.81
Number of infections	63	437
Number per patient	2.25 ± 2.40	1.92 ± 2.19	0.46
Infections caused by gram-negative bacilli
Patients (%)	11 (39.2)	102 (44.3)	0.84
Number per patient	0.86 ± 1.84	0.77 ± 1.25	0.75
Infections caused by gram-positive cocci
Patients (%)	14 (50)	87 (37.8)	0.22
Number per patient	0.64 ± 0.73	0.60 ± 1.009	0.83

Data are presented as mean ± SD or frequencies (%).

Table 3 Type of infections in patients from the polymorphism group and the wild-type group during follow-up

	Polymorphism group (n = 28)	Wild-type group (n = 230)	P value
Spontaneous bacterial peritonitis
Patients (%)	10 (35.7)	81 (35.2)	1.00
Number of spontaneous bacterial peritonitis episodes	15	109
Number per patient	0.54 ± 0.92	0.47 ± 0.79	0.70
Caused by gram-negative bacilli (%)	0 (0)	20 (8.7)	0.14
Caused by gram-positive cocci (%)	3 (10.7)	24 (10.4)	1.00
Culture negative (%)	12 (42.8)	57 (24.8)	0.06
Bacteremia
Patients (%)	4 (14.3)	47 (20.4)	0.61
Number of bacteremia episodes	4	57
Number per patient	0.14 ± 0.36	0.25 ± 0.55	0.41
Caused by gram-negative bacilli (%)	1 (3.6)	26 (11.3)	0.79
Caused by gram-positive cocci (%)	3 (10.7)	31 (13.5)	0.87
Urinary infections
Patients (%)	13 (46.4)	111 (48.3)	1.00
Number of urinary infection episodes	30	209
Number per patient	1.07 ± 2.08	0.91 ± 1.42	0.90
Caused by gram-negative bacilli (%)	10 (35.7)	80 (34.8)	0.92
Caused by gram-positive cocci (%)	7 (25)	49 (21.3)	0.74
Other infections
Patients (%)	9 (32.1)	59 (25.9)	0.50
Pneumonia (%)	5 (17.9)	20 (8.7)	0.16
Bacteriascites (%)	2 (7.1)	15 (6.5)	1.00
Cellulitis (%)	2 (7.1)	13 (5.7)	0.67

Data are presented as mean ± SD or frequencies (%).

Table 4 Univariate and multivariate analysis of baseline characteristics regarding the risk of death during follow-up in all patients

Variables	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age (yr)	1.042 (1.026-1.056)	< 0.001	1.035 (1.016-1.054)	< 0.001
HCV etiology	1.99 (1.385-2.865)	< 0.001
Diabetes mellitus	1.583 (1.097-2.283)	0.010
Active alcohol intake	0.353 (0.230-0.542)	< 0.001	0.568 (0.345-0.935)	0.020
Child-Pugh score	1.170 (1.041-1.317)	0.008	1.263 (1.113-1.432)	< 0.001
MELD score	1.036 (1.007-1.066)	0.010
Previous decompensation	2.33 (1.473-3.690)	< 0.001
Previous ascites	2.50 (1.620-3.860)	< 0.001
Previous encepalophathy	2.794 (1.908-4.092)	< 0.001	2.216 (1.493-3.290)	< 0.001
Hepatocellular carcinoma	2.872 (1.097-4.817)	< 0.001	2.381 (1.411-4.018)	< 0.001
Previous β-blockers	1.727 (1.194-2.498)	0.004
Previous diuretics	1.957 (1.334-2.869)	0.001
Serum creatinine (μmol/L)	1.006 (1.004-1.008)	< 0.001	1.005 (1.002-1.007)	< 0.001
Serum urea (mmol/L)	1.026 (1.013-1.040)	< 0.001
Platelet count (× 109/L)	0.997 (0.995-1.00)	0.032
TLR4 polymorphisms	1.372 (0.770-2.445)	0.280

HCV: Hepatitis C virus; MELD: Model for end-stage liver disease.