CHINAT-CD4 Score Predicts Transplant-Free Survival in Patients with Acute-on-Chronic Liver Failure

Figures & data

Figure 1 Screening of patients according to the APASL-ACLF criteria.

Abbreviations: ACLF, acute-on-chronic liver failure; APASL, Asian Pacific Association for the Study of the Liver; HBV-ACLF, HBV-related ACLF; HIV, Human Immunodeficiency Virus; HCV, hepatitis C virus.

Table 1 Clinical Characteristics of Patients with HBV-ACLF in the Derivation Set

Characteristic	Overall (n=408)	Deceased^† (n=155)	Alive^† (n=253)	p value
Male, n (%)	347 (85.0%)	131 (84.5%)	216 (85.4%)	0.813
Age, (years)	48 (39, 58)	49 (40, 60)	47 (38, 55)	0.113
Precipitating events, n (%)				0.312
HBV reactivation	278 (68.1%)	101 (65.2%)	177 (70.0%)
Active drinking	39 (9.6%)	15 (9.7%)	24 (9.5%)
Hepatotoxic drugs	22 (5.4%)	11 (7.1%)	11 (4.3%)
ALD activation	19 (4.7%)	8 (5.2%)	11 (4.3%)
Bacterial infection	8 (2.0%)	6 (3.9%)	2 (0.8%)
Superimposed HEV	7 (1.72%)	2 (1.29%)	5 (1.98%)
Superimposed HAV	3 (0.74%)	1 (0.64%)	2 (0.79%)
Unknown	32 (7.8%)	10 (6.5%)	22 (8.7%)
Organ failure, n (%)				<0.001
Liver	278 (68.1%)	135 (87.1%)	143 (56.5%)
Coagulation	166 (40.7%)	94 (60.6%)	72 (28.5%)
Cerebral	71 (17.4%)	56 (36.1%)	15 (5.9%)
Kidney	24 (5.9%)	20 (12.9%)	4 (1.6%)
Circulation	3 (0.7%)	3 (1.9%)	0
Lung	2 (0.5%)	2 (1.3%)	0
ALT, (IU/L)	145 (54, 601)	255 (81, 924)	101 (48, 392)	<0.001
AST, (IU/L)	143 (78, 426)	193 (100, 623)	123 (64, 279)	<0.001
TBIL, (μ mol/L)	310 (155, 481)	397 (256, 563)	238 (105, 419)	<0.001
ALB, (g/L)	33 (29, 36)	31 (28, 35)	33 (30, 37)	0.005
GLB, (g/L)	27 (23, 32)	27 (22, 32)	28 (23, 32)	0.049
Cr, (μmol/L)	65 (54, 81)	66 (53, 93)	64 (54, 78)	0.147
WBC, (10^9/L)	6.3 (4.5, 9.3)	6.5 (3.7, 10.1)	5.7 (4.1, 7.9)	<0.001
Neutrophils, (10^9/L)	4.3 (2.7, 7.1)	4.4 (2.8, 6.5)	3.7 (2.4, 5.6)	<0.001
Lymphocytes, (10^9/L)	1.1 (0.7, 1.6)	1.0 (0.7, 1.4)	1.2 (0.8, 1.6)	0.014
INR	2.3 (1.9, 3.2)	2.8 (2.2, 4.1)	2.1 (1.7, 2.6)	<0.001
PCT (ng/mL)	0.8 (0.4, 1.8)	0.9 (0.5, 1.8)	0.6 (0.3, 1.6)	0.007
Lymphocyte subsets (cells/ul)
CD3+ T cells	817 (499, 1114)	681 (436, 983)	881 (555, 1164)	0.001
CD8+ T cells	288 (163, 446)	245 (143, 434)	306 (172, 455)	0.031
CD4+ T cells	439 (267, 640)	360 (254, 529)	475 (297, 681)	<0.001
CD45+ T cells	1166 (795, 1588)	1009 (695, 1472)	1271 (866, 1679)	0.001

Note: ^†28-day Transplant-Free Survival.

Abbreviations: HBV-ACLF, hepatitis B virus-related acute-on-chronic liver failure; HBV, hepatitis B virus; ALD, autoimmune liver disease; HEV, hepatitis E virus; HAV, hepatitis A virus; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; TBIL, Total bilirubin; ALB, Albumin; GLB, Globulin; Cr, Creatinine; WBC, white blood cell count; INR, international normalized ratio; PCT procalcitonin.

Table 2 Seven Risk Factors Associated with the 28-Day Mortality in Patients with HBV-ACLF

Variables	HR [95% CI]	p value
Ln (AST)	1.286 (1.101–1.502)	0.002
Ln (TBIL)	1.509 (1.176–1.935)	0.001
Ln (Cr)	1.377 (1.047–1.811)	0.022
Ln (Neutrophil)	1.609 (1.253–2.067)	<0.001
Ln (INR)	2.107 (1.635–2.715)	<0.001
Ln (CD4+ T cells)	0.546 (0.425–0.701)	<0.001
HE	1.951 (1.600–2.378)	<0.001

Abbreviations: HBV-ACLF, hepatitis B virus-related acute-on-chronic liver failure; HR, hazard ratio; CI, confidence interval; AST, Aspartate aminotransferase; TBIL, Total bilirubin; Cr, Creatinine; INR, international normalized ratio; HE, hepatic encephalopathy.

Table 3 The C-Index of Prognostic Scores for Predicting the 28-/90-Day Mortality in the Derivation Set

Mortality	CHINAT-CD4	COSSH-ACLF IIs	COSSH-ACLFs	CLIF-C ACLFs	MELD	MELD-Na	HINT	AARC
28-day	0.810 (0.778–0.843)	0.778 (0.742–0.815)	0.764 (0.727–0.801)	0.753 (0.716–0.790)	0.729 (0.690–0.768)	0.721 (0.683–0.760)	0.769 (0.729–0.809)	0.761 (0.726–0.796)
*p value		0.005	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001
90-day	0.806 (0.774–0.838)	0.774 (0.739–0.810)	0.761 (0.725–0.797)	0.746 (0.710–0.783)	0.727 (0.690–0.765)	0.720 (0.683–0.757)	0.764 (0.725–0.803)	0.762 (0.728–0.796)
*p value		0.005	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

Note: *p value for comparisons between the CHINAT-CD4 score and the other scores.

Abbreviations: COSSH-ACLFs, Chinese Group on the Study of Severe Hepatitis B-ACLF score; CLIF-C ACLFs, CLIF-Consortium Acute-on-Chronic Liver Failure score; MELD, Model for End-Stage Liver Disease score; MELD-Na, MELD-sodium score; HINT, HINT score; AARC score, APASL ACLF research consortium liver failure score which includes total bilirubin, INR, grade of HE, plasma lactate and serum creatinine reliably predicts the disease severity and outcome.

Figure 2 Risk stratification of the CHINAT-CD4 score. (A) The derivation set for 28-day mortality, (B) The derivation set for 90-day mortality, (C) The validation set of HBV-ACLF for 28-day mortality, (D) The validation set of HBV-ACLF for 90-day mortality, (E) The validation set of non-HBV-ACLF for 28-day mortality, (F) The validation set of non-HBV-ACLF for 90-day mortality. *Number of liver transplant-free patients.

Table 4 The C-Index of Prognostic Scores for Predicting the 28-/90-Day Mortality in the Validation Set

Mortality	CHINAT-CD4	COSSH-ACLF IIs	COSSH-ACLFs	CLIF-C ACLFs	MELD	MELD-Na	HINT	AARC
Validation set of HBV-ACLF
28-day	0.798 (0.751–0.845)	0.740 (0.686–0.795)	0.742 (0.687–0.796)	0.733 (0.680–0.785)	0.720 (0.664–0.777)	0.719 (0.665–0.773)	0.758 (0.704–0.811)	0.755 (0.704–0.806)
*p value		0.006	0.003	0.010	<0.001	<0.001	0.040	0.019
90-day	0.793 (0.747–0.839)	0.736 (0.683–0.789)	0.737 (0.684–0.790)	0.730 (0.678–0.781)	0.713 (0.659–0.768)	0.713 (0.660–0.766)	0.754 (0.701–0.807)	0.749 (0.699–0.800)
*p value		0.005	0.003	0.011	<0.001	<0.001	0.047	0.016
Validation set of Non-HBV-ACLF
28-day	0.790 (0.738–0.842)	0.780 (0.725–0.834)	0.783 (0.730–0.835)	0.745 (0.682–0.808)	0.764 (0.708–0.820)	0.749 (0.688–0.810)	0.754 (0.695–0.814)	0.795 (0.743–0.847)
*p value		0.628	0.673	0.092	0.288	0.152	0.037	0.639
90-day	0.788 (0.737–0.839)	0.779 (0.727–0.832)	0.781 (0.730–0.833)	0.743 (0.683–0.804)	0.760 (0.706–0.815)	0.742 (0.682–0.801)	0.755 (0.697–0.813)	0.794 (0.743–0.846)
*p value		0.668	0.699	0.081	0.251	0.092	0.053	0.682

Note: *p value for comparisons between the CHINAT-CD4 score and the other scores.

Abbreviations: HBV-ACLF, HBV-related acute-on-chronic liver failure; COSSH-ACLFs, Chinese Group on the Study of Severe Hepatitis B-ACLF score; CLIF-C ACLFs, CLIF-Consortium Acute-on-Chronic Liver Failure score; MELD, Model for End-Stage Liver Disease score; MELD-Na, MELD-sodium score; HINT, HINT score; AARC score, APASL ACLF research consortium liver failure score which includes total bilirubin, INR, grade of HE, plasma lactate and serum creatinine reliably predicts the disease severity and outcome.