Prognostic Value of Combined CA19-9 with Aspartate Aminotransferase to Lymphocyte Ratio in Patients with Intrahepatic Cholangiocarcinoma After Hepatectomy

Figures & data

Table 1 Baseline Characteristics of 530 ICC Patients Who Underwent Hepatectomy

Variables	All Patients (n=530)	Derivation Cohort (n=265)	Validation Cohort (n=265)	P-value
Age, <60/≥60	289/241	150/115	139/126	0.383
Gender, male/female	256/274	124/141	132/133	0.543
HBsAg, ±	153/377	78/187	75/190	0.774
Hepatolithiasis, ±	89/441	48/217	41/224	0.486
White blood count, median (IQR)	6.46 (5.28–7.72)	6.34 (5.18–7.72)	6.62 (5.41–7.75)	0.671
Neutrophils, median (IQR)	4.52 (3.22–5.38)	4.12 (3.13–5.36)	5.41 (4.12–6.63)	0.321
Hemoglobin, median (IQR)	134 (125–137)	132 (127–138)	130 (123–136)	0.712
GGT, median (IQR)	69 (33–145)	72 (30–167)	67 (36–125)	0.823
Tumor size, <5/≥5	226/304	118/147	108/177	0.506
Tumor number, single/multiple	373/157	194/71	179/86	0.183
Differentiation, well/moderate-poor	22/508	11/254	11/254	1.000
MVI, ±	54/476	28/237	26/239	0.886
Node invasion, ±	129/401	61/204	68/197	0.544
Perineural invasion, ±	80/450	33/232	47/218	0.114
Cirrhosis, ±	148/382	76/189	72/193	0.772
TNM stage, I–II/III	157/373	88/177	69/196	0.087
CA19-9, <22/≥22	150/380	78/187	72/193	0.630
ALRI grade, low/high	175/355	92/173	83/182	0.460
CAC grade, 1/2/3	64/197/269	35/100/130	29/97/139	0.385

Abbreviations: ICC, intrahepatic cholangiocarcinoma; GGT, gamma glutamyl transferase; MVI, microvascular invasion; CA19-9, carbohydrate antigen 19-9; TNM, tumor-node-metastasis; ALRI, aspartate aminotransferase-to-lymphocyte ratio; CAC, combine ALRI and CA19-9; IQR, interquartile range.

Table 2 Correlation Between CAC Grade and Clinicopathological Characteristics in the Derivation Cohort

Variables	CAC Grade			P-value
	1 (n=35)	2 (n=100)	3 (n=130)
Age, <60/≥60	19/16	60/40	71/59	0.697
Gender, male/female	16/19	44/56	64/66	0.745
HBsAg, ±	9/26	29/71	40/90	0.870
Hepatolithiasis, ±	7/28	19/81	22/108	0.884
White blood count, median (IQR)	132 (124–138)	133 (129–135)	135 (125–141)	0.873
Neutrophils, median (IQR)	3.96 (3.14–5.09)	3.96 (2.92–5.06)	4.29 (3.37–5.88)	0.421
Hemoglobin, median (IQR)	6.35 (5.46–7.58)	6.34 (4.95–7.29)	6.15 (5.18–8.03)	0.526
GGT, median (IQR)	68 (25–126)	59 (26–116)	52 (36–152)	0.723
Tumor size, <5/≥5	22/13	50/50	56/74	0.001
Tumor number, single/multiple	31/4	82/18	81/49	0.001
Differentiation, well/moderate-poor	3/32	4/96	4/126	0.364
MVI, ±	2/33	13/87	13/117	0.467
Node invasion, ±	6/29	16/84	39/91	0.033
Perineural invasion, ±	2/33	10/90	21/109	0.165
Cirrhosis, ±	9/26	31/69	36/94	0.806
TNM stage, I–II/III	17/18	33/67	38/92	0.015

Abbreviations: ICC, intrahepatic cholangiocarcinoma; GGT, gamma glutamyl transferase; MVI, microvascular invasion; CA19-9, carbohydrate antigen 19-9; TNM, tumor-node-metastasis; ALRI, aspartate aminotransferase-to-lymphocyte ratio; CAC, combine ALRI and CA19-9; IQR, interquartile range.

Figure 1 The flow-chart of patient selection.

Table 3 Cox Regression Analysis for OS of ICC Patients in the Derivation Cohort

Variables	Univariate			Multivariate
	HR	95% CI	P	HR	95% CI	P
Age, ≥60/<60	0.999	0.986–1.013	0.884
Gender, female/male	0.931	0.696–1.245	0.631
HBsAg, ±	1.283	0.945–1.744	0.111	1.286	0.908–1.822	0.157
Hepatolithiasis, ±	1.211	0.850–1.725	0.289
White blood count	1.163	0.895–1.222	0341
Neutrophils	1.160	0.982–1.224	0.524
Hemoglobin	0.926	0.782–1.182	0.762
GGT	1.042	0.982–1.052	0.425
Tumor size, ≥5/<5	1.403	1.048–1.877	0.023	1.246	0.918–1.691	0.158
Tumor number, multiple/single	1.718	1.258–2.346	0.001	1.717	1.240–2.376	0.001
Differentiation, moderate-poor/well	7.248	1.797–29.235	0.005	4.859	1.177–19.981	0.029
MVI, ±	1.621	1.044–2.517	0.032	1.257	0.796–1.987	0.327
Node invasion, ±	2.524	1.835–3.472	<0.001	2.087	1.464–2.973	<0.001
Perineural invasion, ±	1.643	1.075–2.511	0.022	1.672	1.046–2.671	0.032
Cirrhosis, ±	0.767	0.563–1.046	0.094	0.724	0.511–1.025	0.069
TNM stage, III/I–II	1.378	1.007–1.887	0.045	1.059	0.747–1.503	0.747
CA19-9, ≥22/<22	2.083	1.463–2.967	<0.001
ALRI grade, high/low	1.894	1.371–2.617	<0.001
CAC grade	1.868	1.485–2.350	<0.001	1.716	1.355–2.172	<0.001

Abbreviations: ICC, intrahepatic cholangiocarcinoma; GGT, gamma glutamyl transferase; MVI, microvascular invasion; CA19-9, carbohydrate antigen 19-9; TNM, tumor-node-metastasis; ALRI, aspartate aminotransferase-to-lymphocyte ratio; CAC, combine ALRI and CA19-9; OS, overall survival.

Table 4 Cox Regression Analysis for DFS of ICC Patients in the Derivation Cohort

Variables	Univariate			Multivariate
	HR	95% CI	P	HR	95% CI	P
Age, ≥60/<60	0.998	0.985–1.011	0.777
Gender, female/male	0.976	0.739–1.290	0.865
HBsAg, ±	1.359	1.012–1.826	0.042	1.367	0.978–1.912	0.067
Hepatolithiasis, ±	1.042	0.735–1.479	0.816
White blood count	1.151	0.964–1.213	0.721
Neutrophils	1.145	0.965–1.210	0.311
Hemoglobin	0.972	0.912–1.124	0.572
GGT	1.021	0.972–1.176	0.325
Tumor size, ≥5/<5	1.390	1.052–1.837	0.021	1.212	0.906–1.621	0.195
Tumor number, multiple/single	1.961	1.453–2.646	<0.001	1.802	1.314–2.472	<0.001
Differentiation, moderate-poor/well	5.858	1.870–18.354	0.002	4.523	1.314–14.505	0.011
MVI, ±	1.735	1.138–2.644	0.010	1.331	0.937–1.891	0.111
Node invasion, ±	1.821	1.331–2.490	<0.001	1.246	0.794–1.955	0.339
Perineural invasion, ±	1.702	1.140–2.543	0.009	2.036	1.302–3.183	0.002
Cirrhosis, ±	0.800	0.593–1.080	0.145	0.781	0.557–1.095	0.152
TNM stage, III/I–II	1.320	0.979–1.781	0.069	1.059	0.759–1.476	0.736
CA19-9, ≥22/<22	1.520	1.104–2.092	0.010
ALRI grade, high/low	1.836	1.356–2.485	<0.001
CAC grade	1.587	1.288–1.956	<0.001	1.499	1.209–1.858	<0.001

Abbreviations: ICC, intrahepatic cholangiocarcinoma; GGT, gamma glutamyl transferase; MVI, microvascular invasion; CA19-9, carbohydrate antigen 19–9; TNM, tumor-node-metastasis; ALRI, aspartate aminotransferase-to-lymphocyte ratio; CAC, combine ALRI and CA19-9; DFS, disease-free survival.

Figure 2 Kaplan-Meier curves for DFS and OS stratified by ALRI (A and D), CA19-9 (B and E), and CAC grade (C and F) in the derivation cohort.

Figure 3 Kaplan-Meier curves for DFS and OS stratified by ALRI (A and D), CA19-9 (B and E), and CAC grade (C and F) in the validation cohort.

Figure 4 Comparison of AUCs of ALRI, CA19-9 and CAC grade in predicting OS (A) and DFS (B) in the derivation cohort.