Peripheral blood lymphocyte subset deficiency in acute-on-chronic liver failure and reconstitution following liver transplantation

Table 1 Baseline characteristics of included patients stratified by disease, mean ± SD/n (%)

Characteristics	Total (n = 83)	ACLF (n = 44)	AD (n = 16)	Cirrhosis (n = 23)	P value
Age in years	48.8 ± 9.4	47.0 ± 8.4	50.9 ± 9.3	50.7 ± 10.9	0.057
Male	67 (80.7)	41 (93.2)	12 (75.0)	14 (60.9)	0.003
Etiology1					0.038
HBV	55 (66.3)	35 (79.6)	9 (56.2)	11 (47.8)
HCV	1 (1.2)	1 (2.3)	0	0
Alcohol	8 (9.6)	2 (4.5)	3 (18.8)	3 (13.0)
Autoimmune	11 (13.3)	3 (6.8)	3 (18.8)	5 (21.8)
Mixed	5 (6.0)	3 (6.8)	1 (6.2)	1 (4.4)
Other	3 (3.6)	0	0	3 (13.0)
Laboratory data
Albumin in g/L	33.8 ± 5.4	34.4 ± 4.9	31.5 ± 5.9	34.5 ± 5.9	0.156
ALT in U/L, median IQR	42.0 (26.0-86.0)	56.5 (37.3-98.3)	37.5 (27.0-87.3)	26.0 (16.0-38.0)	< 0.001
AST in U/L, median IQR	70.0 (45.0-115.0)	99.5 (53.8-120.8)	86.0 (49.5-183.5)	41.0 (30.0-52.0)	< 0.001
TB in μmol/L	301.9 ± 240.7	461.1 ± 180.4	241.9 ± 195.9	39.0 ± 26.0	< 0.001
Creatinine in mg/dL, median IQR	0.7 (0.6-1.1)	0.8 (0.6-1.4)	0.7 (0.6-0.9)	0.7 (0.5-1.3)	0.424
Serum urea in mmol/L, median IQR	5.6 (3.8-7.9)	5.7 (3.8-9.1)	5.5 (4.1-7.5)	5.5 (3.6-7.1)	0.833
INR, median IQR	1.9 (1.4-2.6)	2.5 (2.0-3.0)	1.6 (1.4-2.0)	1.3 (1.2-1.6)	< 0.001
WBC as 109/L, median IQR	5.0 (3.5-7.9)	6.7 (4.3-8.5)	4.4 (2.2-6.6)	3.6 (2.6-4.2)	< 0.001
Neutrophil as 109/L, median IQR	3.4 (2.2-5.5)	4.7 (3.0-6.9)	2.9 (1.5-4.7)	2.1 (1.6-2.8)	< 0.001
Perioperative complications
Infection	43 (51.8)	24 (54.5)	7 (43.8)	12 (52.2)	0.800
PNF	4 (4.8)	3 (6.8)	0 (0)	1 (4.3)	0.811
EAD	31 (37.3)	20 (45.5)	2 (12.5)	9 (39.1)	0.061

¹For acute-on-chronic liver failure etiology, “mixed” refers to patients suffering from two or more types of chronic liver diseases, while “others” indicates chronic liver diseases other than hepatitis B virus, hepatitis C virus, alcohol-associated liver disease, and autoimmune liver disease.

ACLF: Acute-on-chronic liver failure; AD: Acute decompensation; HCV: Hepatitis C virus; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TB: Total bilirubin; INR: International normalized ratio; WBC: White blood cell; EAD: Early allograft dysfunction; PNF: Primary non-function; IQR: Interquartile range.

Table 2 Baseline characteristics of patients with acute-on-chronic liver failure stratified by severity, mean ± SD/n (%)

Characteristics	ACLF-1 (n = 12)	ACLF-2 (n = 22)	ACLF-3 (n = 10)	P value
Age in years	43.5 ± 8.2	47.9 ± 7.1	49.3 ± 10.5	0.213
Male	10 (83.3)	21 (95.5)	10 (100.0)	0.301
Etiology1				0.362
HBV	9 (75)	17 (77.3)	9 (90.0)
HCV	1 (8.3)	0	0
Alcohol	0	1 (4.5)	1 (10.0)
Autoimmune	2 (16.7)	1 (4.5)	0
Mixed	0	3 (13.6)	0
Other	0	0	0
Laboratory data
Albumin in g/L	34.0 ± 6.0	35.1 ± 5.0	33.2 ± 3.3	0.585
ALT in U/L, median IQR	70.0 (39.8-103.3)	49.0 (36.5-78.0)	93.0 (28.5-163.3)	0.304
AST in U/L, median IQR	107.5 (57.5-158.3)	101.0 (75.3-120.3)	58.0 (50.8-79.5)	0.126
TB in μmol/L	455.3 ± 273.0	504.7 ± 133.9	372.0 ± 94.71	0.155
Creatinine in mg/dL, median IQR	1.3 (0.7-2.0)	0.7 (0.6-1.0)	0.7 (0.5-1.3)	0.142
Serum urea in mmol/L, median IQR	10.3 (5.7-18.3)	5.4 (4.1-7.8)	4.1 (2.9-6.2)	0.039
INR, median IQR	1.9 (1.5-2.2)	2.6 (2.3-3.0)	3.3 (2.7-4.9)	< 0.001
WBC as 109/L, median IQR	5.7 (4.1-7.1)	6.8 (4.0-8.6)	8.2 (6.7-9.4)	0.113
Neutrophil as 109/L, median IQR	3.9 (2.7-4.7)	4.8 (2.7-7.0)	5.7 (4.6-8.2)	0.183
Organ failure
Liver	10 (83.3)	22 (100.0)	10 (100.0)	0.117
Kidney	2 (16.7)	2 (9.1)	2 (20.0)	0.614
Coagulation	0 (0)	15 (68.2)	9 (90.0)	< 0.001
Brain	0 (0)	5 (22.7)	9 (90.0)	< 0.001
Respiratory	0 (0)	0 (0)	2 (20.0)	0.048
Circulation	0 (0)	0 (0)	1 (10.0)	0.227
Predictive scores
CTP	10.8 ± 1.2	11.4 ± 1.0	12.7 ± 1.3	0.001
ALBI	-1.2 ± 0.4	-1.2 ± 0.4	-1.1 ± 0.3	0.549
CLIF-C OF	9.0 (8.3-10.0)	11.0 (10.0-11.0)	12.0 (12.0-13.3)	< 0.001
CLIF-C ACLF	39.3 (33.5-40.9)	44.3 (42.8-47.4)	54.3 (52.0-58.8)	< 0.001
MELD	27.3 ± 5.0	31.0 ± 4.0	32.5 ± 7.4	0.050
MELD-Na	28.2 ± 5.1	32.0 ± 3.6	32.5 ± 7.4	0.077
Perioperative complications
Infection	8 (66.7)	8 (36.4)	8 (80.0)	0.054
PNF	0 (0)	0 (0)	3 (30.0)	0.009
EAD	4 (33.3)	8 (36.4)	8 (80.0)	0.054

¹For acute-on-chronic liver failure etiology, “mixed” refers to patients suffering from two or more types of chronic liver diseases, while “others” indicates chronic liver diseases other than hepatitis B virus, hepatitis C virus, alcohol-associated liver disease, and autoimmune liver disease.

ACLF: Acute-on-chronic liver failure; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HCV: Hepatitis C virus; HBV: Hepatitis B virus; TB: Total bilirubin; INR: International normalized ratio; WBC: White blood cell; CTP: Child-Turcotte-Pugh; ALBI: Albumin-bilirubin; CLIF-C: Chronic liver failure-consortium; OF: Organ failure; MELD: Model for end-stage liver disease; MELD-Na: Model for end-stage liver disease-sodium; EAD: Early allograft dysfunction; PNF: Primary non-function; IQR: Interquartile range.

Table 3 Association between peripheral blood lymphocyte subset levels before liver transplantation and long-term survival

PBLS	HR (95%CI)	P value
CD3+ T cell	1.00 (1.00-1.00)	0.773
CD4+ T cell	1.00 (1.00-1.00)	0.995
CD8+ T cell	1.00 (0.99-1.00)	0.725
B cell	0.99 (0.96-1.01)	0.331
NK cell	1.00 (1.00-1.00)	0.205

CD: Cluster of differentiation; CI: Confidence interval; HR: Hazard ratio; NK: Natural killer; PBLS: Peripheral blood lymphocyte subset.

Table 4 Association between peripheral blood lymphocyte subset levels before liver transplantation and perioperative complications

Variables	Univariate analysis		Multivariable analysis
	OR (95%CI)	P value	OR (95%CI)	P value
EAD
CD3+ T cell	1.00 (1.00-1.00)	0.329
CD4+ T cell	1.00 (1.00-1.01)	0.151
CD8+ T cell	1.00 (1.00-1.00)	0.815
B cell	1.00 (1.00-1.01)	0.117
NK cell	1.01 (0.99-1.03)	0.366
PNF
CD3+ T cell	1.00 (0.99-1.00)	0.317
CD4+ T cell	0.99 (0.98-1.00)	0.205
CD8+ T cell	1.00 (0.99-1.00)	0.895
B cell	1.00 (1.00-1.01)	0.051
NK cell	0.95 (0.82-1.01)	0.275
Infection
CD3+ T cell	1.00 (1.00-1.00)	0.126
CD4+ T cell	1.00 (0.99-1.00)	0.142
CD8+ T cell	1.00 (0.99-1.00)	0.120
B cell	1.00 (1.00-1.00)	0.435
NK cell	0.96 (0.93-0.99)	0.016	0.97 (0.94-1.00)	0.067

CD: Cluster of differentiation; OR: Odds ratio; CI: Confidence interval; EAD: Early allograft dysfunction; NK: Natural killer; PNF: Primary non-function.