Efficacy and Safety of Transarterial Chemoembolization for the Treatment of Unresectable Hepatocellular Carcinoma Associated with Bile Duct Tumor Thrombus: A Real-World Retrospective Cohort Study

Figures & data

Figure 1 Flowchart of screening all HCC patients with BDTT who underwent either TACE or CM as initial treatment.

Abbreviations: HCC, hepatocellular carcinoma; BDTT, bile duct tumor thrombus; TACE, transarterial chemoembolization; CM, conservative management; ECOG-PS, Eastern Cooperative Oncology Group performance status; RFA, radiofrequency ablation; RT, radiotherapy.

Table 1 Baseline Characteristics of HCC Patients with BDTT

Clinical Variables	TACE Group (n=40)	CM Group (n=60)	Statistic	P
Age, years	55 (45–62)	55 (42–61)	0.232	0.816
Sex			0.009	0.923
Male	31 (77.5%)	46 (76.7%)
Female	9 (22.5%)	14 (23.3%)
Child–Pugh class			28.976	< 0.001
A	28 (70.0%)	10 (16.7%)
B	12 (30.0%)	50 (83.3%)
HBsAg			0.082	0.774
Positive	31 (77.5%)	45 (75.0%)
Negative	9 (22.5%)	15 (25.0%)
HBeAg			0.915	0.339
Positive	9 (22.5%)	9 (15.0%)
Negative	31 (77.5%)	51 (85.0%)
Anti-HCV			0.916	0.338
Positive	2 (5.0%)	1 (1.7%)
Negative	38 (95.0%)	59 (98.3%)
HBV DNA, copies/mL			0.032	0.857
≤ 1000	28 (70.0%)	43 (71.7%)
> 1000	12 (30.0%)	17 (28.3%)
WBC, 10^9/L	5.2 (3.8–7.2)	6.4 (4.8–7.6)	1.787	0.074
HGB, g/L	128 (119–134)	123 (108–136)	0.827	0.408
PLT, 10^9/L	169 (120–220)	177 (128–263)	0.697	0.486
ALB, g/L	37.7 (4.5)	36.2 (5.8)	1.555	0.123
TBil on admission, μmol/L	27.3 (19.7–44.1)	211.8 (82.8–334.4)	6.294	< 0.001
ALT (U/L)	50.5 (29.8–104.8)	68.6 (47.6–116.8)	1.763	0.078
GGT (U/L)	324.0 (188.3–523.3)	269.5 (126.0–527.0)	1.031	0.303
ALP (U/L)	179.5 (133.5–269.5)	198.0 (141.0–308.8)	1.270	0.204
PT (s)	12.3 (11.5–13.8)	12.3 (11.6–14.0)	0.011	0.992
Scr (μmol/L)	65.3 (14.1)	64.1 (16.6)	0.398	0.691
CA 19–9 (U/mL)	71.5 (29.9–145.2)	259.0 (56.5–932.6)	3.380	0.001
AFP (ng/mL)			0.245	0.621
≤ 400	24 (60.0%)	33 (55.0%)
> 400	16 (40.0%)	27 (45.0%)
Tumor diameter (cm)	7.0 (4.5–8.9)	4.7 (3.1–6.8)	2.396	0.017
Tumor number			6.566	0.010
Solitary	26 (65.0%)	52 (86.7%)
Multiple	14 (35.0%)	8 (13.3%)
Major vascular invasion			8.488	0.004
Presence	10 (25.0%)	3 (5.0%)
Absence	30 (75.0%)	57 (95.0%)

Abbreviations: HCC, hepatocellular carcinoma; BDTT, bile duct tumor thrombus; TACE, transarterial chemoembolization; CM, conservative management; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HCV, hepatitis C virus; HBV DNA, hepatitis B virus deoxyribonucleic acid; WBC, white blood cell; HGB, hemoglobin; PLT, platelet; ALB, albumin; TBil, total bilirubin; ALT, alanine aminotransferase; GGT, γ-glutamyltransferase; ALP, alkaline phosphatase; PT, prothrombin time; Scr, serum creatinine; CA19-9, carbohydrate antigen 19–9; AFP, α-fetoprotein.

Table 2 Univariate and Multivariate Analysis for Prognostic Factors of OS in HCC Patients with BDTT

Clinical Variables	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	P	HR (95% CI)	P
Treatment allocation, TACE vs CM	0.365 (0.238–0.560)	< 0.001	0.421 (0.243–0.730)	0.002
Age (per 1 year increase)	0.998 (0.979–1.018)	0.871
Sex, male vs female	1.006 (0.627–1.614)	0.979
Child–Pugh class, B vs A	1.639 (1.081–2.485)	0.020	2.529 (1.300–4.920)	0.006
HBsAg, positive vs negative	1.063 (0.664–1.700)	0.800
HBeAg, positive vs negative	1.457 (0.845–2.512)	0.176
Anti-HCV, positive vs negative	2.854 (0.685–11.889)	0.150
HBV DNA, >1000 vs ≤1000 copies/mL	1.377 (0.875–2.167)	0.167
WBC (per 1*10^9/L increase)	1.077 (0.995–1.165)	0.066
HGB (per 1 g/L increase)	1.001 (0.994–1.009)	0.781
PLT (per 1*10^9/L increase)	1.001 (0.999–1.003)	0.352
ALB (per 1 g/L increase)	0.990 (0.951–1.032)	0.647
TBil on admission (per 1 μmol/L increase)	1.006 (1.004–1.007)	< 0.001	1.007 (1.004–1.009)	< 0.001
ALT (per 1 U/L increase)	0.999 (0.996–1.002)	0.366
GGT (per 1 U/L increase)	1.000 (0.999–1.001)	0.652
ALP (per 1 U/L increase)	1.001 (0.999–1.002)	0.354
PT (per 1 second increase)	1.030 (0.941–1.126)	0.523
Scr (per 1 μmol/L increase)	1.006 (0.993–1.019)	0.357
CA 19–9, > 40 vs ≤ 40 U/mL	1.276 (0.800–2.038)	0.306
AFP, > 400 vs ≤ 400 ng/mL	1.051 (0.699–1.581)	0.811
Tumor diameter, > 5 vs ≤ 5 cm	1.264 (0.845–1.890)	0.255
Tumor number, multiple vs solitary	1.036 (0.642–1.673)	0.884
Major vascular invasion, yes vs no	1.519 (0.842–2.743)	0.165

Abbreviations: HCC, hepatocellular carcinoma; BDTT, bile duct tumor thrombus; TACE, transarterial chemoembolization; CM, conservative management; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; HCV, hepatitis C virus; HBV DNA, hepatitis B virus deoxyribonucleic acid; WBC, white blood cell; HGB, hemoglobin; PLT, platelet; ALB, albumin; TBil, total bilirubin; ALT, alanine aminotransferase; GGT, γ-glutamyltransferase; ALP, alkaline phosphatase; PT, prothrombin time; Scr, serum creatinine; CA19-9, carbohydrate antigen 19–9; AFP, α-fetoprotein.

Figure 2 Kaplan–Meier curves of overall survival in HCC patients with BDTT who underwent TACE or CM (P < 0.001).

Abbreviations: HCC, hepatocellular carcinoma; BDTT, bile duct tumor thrombus; TACE, transarterial chemoembolization; CM, conservative management.

Figure 3 Subgroup analysis of overall survival in HCC patients with BDTT who underwent initial TACE or CM stratified using baseline liver function (Child–Pugh class A or B) and total bilirubin concentration (≤51 or >51 μmol/L). (A) survival curves for HCC patients with BDTT with Child–Pugh class A liver function (P < 0.001); (B) survival curves for HCC patients with BDTT with Child–Pugh class B liver function (P = 0.003); (C) survival curves for HCC patients with BDTT with total bilirubin level ≤51 μmol/L (P = 0.079); (D) survival curves for HCC patients with BDTT with total bilirubin level >51 μmol/L (P = 0.005).

Abbreviations: HCC, hepatocellular carcinoma; BDTT, bile duct tumor thrombus; TACE, transarterial chemoembolization; CM, conservative management.