Liver Injury and Its Impact on Prognosis in Patients with HBV-Related Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Combined with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors

Figures & data

Table 1 Baseline Characteristics of Enrolled Patients

Characteristics	Hepatotoxicity (n=52)	Without Hepatotoxicity (n=67)	P
Age, years	57 (35–82)	55 (19–78)	0.563
≥60	21 (45.7%)	25 (54.3%)	0.733
<60	31 (42.5%)	42 (57.5%)
Gender			1.000
Male	48 (44.0%)	61 (56.0%)
Female	4 (40.0%)	6 (60.0%)
History of alcoholism			0.421
Yes	15 (50.0%)	15 (50.0%)
No	37 (41.6%)	52 (58.4%)
Antiviral prophylaxis			0.001
Yes	34 (35.8%)	61 (64.2%)
No	18 (75.0%)	6 (25.0%)
HBsAg			0.015
Seropositive	46 (40.7%)	67 (59.3%)
Seronegative	6 (100.0%)	0 (0.0%)
HBeAg			0.155
Seropositive	4 (26.7%)	11 (73.3%)
Seronegative	48 (46.2%)	56 (53.8%)
Child-pugh grade			0.421
A	44 (42.3%)	60 (57.7%)
B	8 (53.3%)	7 (46.7%)
ALBI grade			1.000
1	25 (44.6%)	31 (55.4%)
2	26 (43.3%)	34 (56.7%)
3	1 (33.3%)	2 (66.7%)
BCLC			0.767
B	32 (42.7%)	43 (57.3%)
C	20 (45.5%)	24 (54.5%)
HBV DNA, IU/mL	0 (0–3.89×10^6)	0 (0–3.89×10^6)	0.540
Undetectable	28 (45.2%)	34 (54.8%)	0.737
Detectable	24 (42.1%)	33 (57.9%)
>2000	11 (36.7%)	19 (63.3%)	0.369
≤2000	41 (46.1%)	48 (53.9%)
ALT, U/L	37.5 (8–123)	34 (12–107)	0.556
AST, U/L	42 (17–135)	40 (15–225)	0.575
TBil, μmol/L	17 (2.8–55.6)	16.5 (5.8–78.2)	0.607
ALB, g/L	39.2±5.2	38.8±5.0	0.690
AFP, ng/mL	282.6 (2.46–21,685)	142.2 (1–164,935)	0.238
≥200	29 (48.3%)	31 (51.7%)	0.304
<200	23 (39.0%)	36 (61.0%)
WBC, ×10^9/L	4.8 (2.6–10.1)	5.4 (1.4–32)	0.125
NLR			0.802
>2.5	33 (42.9%)	44 (57.1%)
≤2.5	19 (45.2%)	23 (54.8%)
PLR	114.2 (31.4–266)	115 (37.1–696.7)	0.510

Abbreviations: AFP, alpha fetoprotein; ALB, albumin; ALBI, albumin-bilirubin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; NLR, neutrophil to lymphocyte ratio; TBil, total bilirubin; WBC, leukocyte; PLR, platelet to lymphocyte ratio.

Figure 1 The patients flowchart.

Abbreviations: Anti-HBc, antibody to hepatitis B core antigen; HBV, hepatitis B virus; HCC, hepatocarcinoma; HCV, hepatitis C virus; ICIs, immune checkpoint inhibitors; TACE, transarterial chemoembolization; TKIs, tyrosine kinase inhibitors.

Table 2 Univariate and Multivariate Logistic Regression Analysis for Risk Factors of Liver Injury

	Univariate		Multivariate
	OR (95% CI)	P	OR (95% CI)	P
Age group (≥60 years)	1.138 (0.541–2.392)	0.733
Gender (male)	1.180 (0.315–4.420)	0.806
History of alcoholism (yes)	1.405 (0.612–3.225)	0.422
Antiviral prophylaxis (yes)	0.186 (0.067–0.513)	0.001	0.149 (0.050–0.442)	0.001
HBsAg (+)	0.000 (0.000-NA)	0.999
HBeAg (+)	0.424 (0.127–1.419)	0.164
HBV DNA (detectable)	0.883 (0.427–1.825)	0.737
HBV DNA (>2000 IU/mL)	0.678 (0.289–1.588)	0.371
ALT, U/L	1.005 (0.991–1.020)	0.453
TBil, μmol/L	1.010 (0.978–1.043)	0.544
Child-pugh (B)	1.558 (0.526–4.619)	0.432
ALBI grade
1*		0.927
2	0.948 (0.455–1.975)	0.887
3	0.620 (0.053–7.240)	0.703
BCLC (C)	1.120 (0.529–2.369)	0.767
AFP (>200 ng/mL)	1.464 (0. 707–3.033)	0.305
WBC, ×10^9/L	0.867 (0.748–1.005)	0.058	0.814 (0.677–0.980)	0.030
NLR (>2.5)	0.908 (0.426–1.935)	0.802
PLR	0.999 (0.994–1.003)	0.630

Note: *Used as the reference category.

Abbreviations: AFP, alpha fetoprotein; ALBI, albumin-bilirubin; ALT, alanine aminotransferase; BCLC, Barcelona Clinic Liver Cancer; CI, confidence intervals; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; NLR, neutrophil to lymphocyte ratio; OR, odds ratio; TBil, total bilirubin; WBC, leukocyte; PLR, platelet to lymphocyte ratio.

Table 3 Univariate and Multivariate Analysis for Prognostic Factors of Survival Time

	Univariate		Multivariate
	HR (95% CI)	P	HR (95% CI)	P
Age group (≥60 years)	0.369 (0.186–0.730)	0.004	0.422 (0.211–0.844)	0.015
Gender (male)	1.314 (0.407–4.245)	0.648
History of alcoholism (yes)	0.772 (0.371–1.607)	0.490
Antiviral prophylaxis (yes)	1.137 (0.561–2.302)	0.722
HBsAg (+)	1.548 (0.374–6.406)	0.546
HBeAg (+)	0.432 (0.133–1.397)	0.161
HBV DNA (detectable)	1.911 (1.055–3.463)	0.033
HBV DNA (>2000 IU/mL)	1.747 (0.928–3.290)	0.084
Child-pugh (B)	2.673 (1.271–5.622)	0.010	2.450 (1.162–5.164)	0.019
ALBI grade
1*		0.053
2	2.151 (1.158–3.994)	0.015
3	1.779 (0.233–13.572)	0.578
AFP (≥200 ng/mL)	3.209 (1.693–6.085)	<0.001	2.392 (1.241–4.611)	0.009
NLR (>2.5)	2.041 (1.033–4.033)	0.040
Liver injury (yes)	2.080 (1.137–3.808)	0.018	1.912 (1.031–3.546)	0.040

Note: *Used as the reference category.

Abbreviations: AFP, alpha fetoprotein; ALBI, albumin-bilirubin; CI, confidence intervals; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; NLR, neutrophil to lymphocyte ratio; HR, hazard ratio.

Figure 2 Kaplan–Meier curve for overall survival (OS) time (A) in all enrolled patients, (B) in patients with or without liver injury, (C) in patients with different severity of liver injury.

Abbreviation: MST, median survival time.