Bacterial infection triggers and complicates acute-on-chronic liver failure in patients with hepatitis B virus-decompensated cirrhosis: A retrospective cohort study

Table 1 Demographic and clinical characteristics, laboratory tests, and severity scores of patients on admission

Characteristic	All patients (n = 1281)	Without BI (n = 921)	With BI (n = 360)	P value
Median age (IQR) -yr	51 (42-57)	52 (43-57)	50 (42-57)	0.16
Male sex (%)	1012 (79)	726 (78.8)	286 (79.4)	0.88
Concomitant etiology of cirrhosis (%)
Alcohol	142 (11.1)	102 (11.1)	40 (11.1)	1.00
Others	48 (3.7)	36 (3.9)	12 (3.3)	0.74
HBeAg positive HBV (%)1	421/1122 (37.5)	298/794 (37.5)	123/328 (37.5)	1.00
Experience of anti-HBV treatment (%)1	284/1176 (24.2)	183/851 (21.5)	101/325 (31.1)	< 0.001
Decompensations (%)2
Ascites	1099 (85.8)	773 (83.9)	326 (90.6)	< 0.01
Jaundice	534 (41.7)	297 (32.2)	237 (65.8)	< 0.001
Gastrointestinal variceal bleeding	336 (26.2)	280 (30.4)	56 (15.6)	< 0.001
Hepatic encephalopathy	190 (14.8)	82 (8.9)	108 (30)	< 0.001
ACLF at admission (%)	284 (22.2)	130 (14.1)	154 (42.8)	< 0.001
Median value for laboratory tests (IQR)
Log10 HBV DNA (copies/mL)3	4.7 (3.1-6.1)	4.8 (3-6.2)	4.6 (3.1-5.7)	0.33
Hemoglobin (g/L)	103 (83-121)	102 (82-119)	107 (87-127)	< 0.001
White cell count: × 109 cells/L	4.7 (2.9-7.5)	4.2 (2.7-6.1)	6.9 (4.3-10.9)	< 0.001
Platelet count: × 109 cells/L	63 (40-102)	60 (40-96)	70 (42-117.5)	< 0.01
International normalized ratio	1.6 (1.3-2)	1.4 (1.3-1.9)	1.8 (1.5-2.6)	< 0.001
Serum sodium (mmol/L)	136 (131.2-139)	136 (132.3-139.3)	134 (129-137)	< 0.001
Serum creatinine (mg/dL)	0.8 (0.7-1)	0.8 (0.7-1)	0.8 (0.6-1.1)	0.20
Aspartate aminotransferase (IU/L)	67 (42-124)	60 (40-107)	97 (56.5-192)	< 0.001
Alanine aminotransferase (IU/L)	47 (30-97)	42 (29-80)	67 (37-185.8)	< 0.001
Total bilirubin (mg/dL)	3.4 (1.5-15.5)	2.6 (1.4-8)	10.9 (3-27.4)	< 0.001
Serum albumin (g/dL)	2.8 (2.5-3.2)	2.9 (2.5-3.3)	2.8 (2.4-3.1)	< 0.001
Median value for severity scores (IQR)
Child-Pugh	11 (9-12)	10 (8-12)	12 (10-13)	< 0.001
MELD	16.8 (11.8-25.5)	14.8 (11.1-22.3)	24.4 (17.1-30.2)	< 0.001

¹Number/number of patients with available data.

²Some patients had more than one decompensating event.

³Analysis was performed in 1031 patients with available data. IQR: Interquartile range; ACLF: Acute-on-chronic liver failure; MELD: Model for end stage liver disease; HBV: Hepatitis B virus.

Table 2 Characteristics of bacterial infection according to in-hospital outcome

Characteristic	All patient (n = 1281)	Survivors (n = 1101)	Non-survivors (n = 180)	P value1
Bacterial infection	360 (28.1)	247 (22.4)	113 (62.8)	< 0.001
Source of acquisition
Community-acquired	76 (5.9)	58 (5.3)	18 (10)	0.02
Healthcare-associated	136 (10.6)	89 (8.1)	47 (26.1)	< 0.001
Nosocomial infection	162 (12.6)	107 (9.7)	55 (30.6)	< 0.001
Single site
Pneumonia	126 (9.8)	75 (6.8)	51 (28.3)	< 0.001
Spontaneous bacterial peritonitis	69 (5.4)	47 (4.3)	22 (12.2)	< 0.001
Urinary tract infection	29 (2.3)	26 (2.4)	3 (1.7)	0.79
Spontaneous bacteremia	16 (1.3)	14 (1.3)	2 (1.1)	1.00
Skin or soft tissue infection	9 (0.7)	7 (0.6)	2 (1.1)	0.37
Others2	17 (1.3)	15 (1.4)	2 (1.1)	1.00
Multi sites	34 (2.7)	20 (1.8)	14 (7.8)	< 0.001
Unknown site3	60 (4.7)	43 (3.9)	17 (9.4)	< 0.01

¹P value corresponds to the comparisons between survivors and non-survivors;

²Other infections included cholangitis (n = 7), enterocolitis (n = 5), secondary bacterial peritonitis (n = 1), appendicitis (n = 1), spontaneous bacterial empyema (n = 2), and spleen abscess (n = 1);

³Unknown site denotes the presence of fever and leukocytosis requiring antibiotic therapy without any identifiable source.

Table 3 Univariate competing risk analysis of risk factors for in-hospital survival

Parameters	Without ACLF at admission		ACLF at admission
	sHR (95%CI)	P value	sHR (95%CI)	P value
Age (yr)	1.01 (0.99-1.03)	0.22	1.02 (1.00-1.03)	0.03
Male sex (%)	1.37 (0.74-2.54)	0.32	0.97 (0.59-1.60)	0.91
Ascites (%)	2.88 (1.05-7.93)	0.04	1.11 (0.57-2.17)	0.76
V Gastrointestinal variceal bleeding (%)	0.65 (0.37-1.14)	0.13	0.64 (0.22-1.81)	0.40
Hepatic encephalopathy (%)	0.96 (0.36-2.57)	0.93	1.90 (1.28-2.83)	< 0.01
Jaundice (%)	5.10 (3.10-8.39)	< 0.001	2.45 (1.20-5.03)	< 0.001
Bacterial infection (%)	4.94 (3.08-7.94)	< 0.001	2.34 (1.52-3.59)	< 0.001
Pneumonia (%)	4.79 (2.86-8.03)	< 0.001	2.06 (1.39-3.05)	< 0.001
Spontaneous bacterial peritonitis (%)	4.05 (2.19-7.48)	< 0.001	1.49 (0.88-2.53)	0.13
Urinary tract infection (%)	0.94 (0.23-3.81)	0.93	1.34 (0.67-2.68)	0.41
HBeAg positive HBV (%)	0.92 (0.56-1.54)	0.76	1.08 (0.78-1.63)	0.70
Log10 HBV DNA (copies/mL)	1.04 (0.90-1.21)	0.57	1.10 (0.96-1.25)	0.18
White cell count (× 109 cells/L)	1.11 (1.07-1.16)	< 0.001	1.04 (1.01-1.06)	0.02
Total bilirubin (mg/dL)	1.05 (1.03-1.06)	< 0.001	1.02 (1.01-1.03)	< 0.01
Serum creatinine (mg/dL)	1.87 (0.59-5.93)	0.29	1.05 (0.96-1.15)	0.25
International normalized ratio	1.97 (1.56-2.49)	< 0.001	1.09 (0.93-1.29)	0.31
Serum albumin (g/dL)	0.41 (0.27-0.64)	< 0.001	0.63 (0.45-0.88)	< 0.01
Serum sodium (mmol/L)	0.91 (0.88-0.93)	< 0.001	0.98 (0.95-1.01)	0.14

sHR: Subdistribution hazard ratio; CI: Confidence interval; ACLF: Acute-on-chronic liver failure; HBV: Hepatitis B virus.

Table 4 Multivariate competing risk analysis of risk factors for in-hospital survival

Parameters	Estimate	Standard error	sHR (95%CI)	P value
	Without ACLF at admission
Bacterial infection	1.1872	0.2708	3.28 (1.93-5.57)	< 0.001
Total bilirubin at admission	0.0292	0.0104	1.03 (1.01-1.05)	< 0.01
Albumin at admission	-0.7695	0.2357	0.46 (0.29-0.74)	< 0.01
Sodium at admission	-0.0738	0.0178	0.93 (0.9-0.96)	< 0.001
	ACLF at admission
Pneumonia	0.6250	0.2106	1.87 (1.24-2.82)	< 0.01
Hepatic encephalopathy	0.5453	0.2068	1.73 (1.15-2.59)	< 0.01
Total bilirubin at admission	0.0277	0.0081	1.03 (1.01-1.04)	< 0.001
Albumin at admission	-0.7110	0.1945	0.49 (0.34-0.72)	< 0.001

sHR: Subdistribution hazard ratio; CI: Confidence interval; ACLF: Acute-on-chronic liver failure.