Hepatitis B virus infection: A favorable prognostic factor for intrahepatic cholangiocarcinoma after resection

Table 1 Surgical procedures performed for patients

Operation	n	Combination resection	n
Partial hepatectomy	111	Abdominal wall focus resection	1
Left hemihepatectomy	30	Diaphragm wedge resection	8
Right hemihepatectomy	14	Right adrenalectomy	2
Left extended hemihepatectomy	2	Omentumectomy	7
Caudate segmentectomy	5	Gallbladder removal	3

Table 2 Univariate and multivariate analyses of prognostic factors for overall survival rate of intrahepatic cholangiocarcinoma patients included in this study

Factor	n	Survival rate (%)		P value		Hazard ratio	95% CI
		1-yr	3-yr	Univariate analysis	Multivariate analyses
Age (yr)
> 65	28	71.4	33.7
≤ 65	127	58.3	31.8	0.590	NA	NA	NA
Sex
Female	53	64.2	29.4
Male	102	58.8	33.7	0.973	NA	NA	NA
HBV infection
No	68	45.6	20.5
Yes	87	72.4	41.8	0.003	0.044	4.075	0.418-0.987
Cirrhosis
Yes	45	62.6	32.7
No	110	60	31.9	0.964	NA	NA	NA
Hepatolithiasis
Yes	12	16.7	< 0.01
No	143	64.3	34.4	0.001	0.039	4.254	1.040-4.614
Liver schistosomiasis
Yes	7	57.1	14.3
No	148	60.8	33	0.063	0.612	0.257	0.532-2.920
ALT
≤ 42 U/L	113	60.2	32.9
> 42 U/L	42	61.9	29.8	0.956	NA	NA	NA
AST
≤ 37 U/L	102	58.8	32.7
> 37 U/L	53	64.2	30.5	0.949	NA	NA	NA
TBIL
≤ 20 μmol/L	119	60.5	30.7
> 20 μmol/L	36	61.1	37.5	0.355	NA	NA	NA
r-GT
≤ 64 U/L	68	67.6	44.7
> 64 U/L	87	55.2	22.4	0.003	0.102	2.667	0.918-2.547
ALP
≤ 119 U/L	89	71.9	44.5
> 119 U/L	66	45.5	15.8	< 0.001	0.386	0.75	0.758-2.047
AFP
≤ 20 μg/L	125	58.4	32.8
> 20 μg/L	30	70	29.3	0.788	NA	NA	NA
CA19-9
≤ 37 U/mL	66	66.7	41.7
> 37 U/mL	89	56.2	24.7	0.035	0.534	0.388	0.555-1.356
Tumor number
Single	137	63.5	36
Multiple	18	38.9	11.1	0.007	0.188	1.734	0.811-2.913
Tumor size
< 5 cm	58	74.1	42.1
≥ 5 cm	97	52.6	26.1	0.014	0.563	0.335	0.737-1.754
Tumor location
Left lobe	55	52.7	32.2
Right lobe	90	70	35.8
Both lobes	10	20	< 0.01	0.008	0.314	1.015	0.962-1.128
Microscopic satellite lesion
Yes	39	43.6	11.5
No	116	66.4	38.9	< 0.001	0.002	9.418	1.287-3.140
Capsule formation
Yes	17	64.7	45.8
No	138	60.1	30.5	0.251	NA	NA	NA
Tumor differentiation
Well to moderately	118	61.9	33.3
Poorly	37	56.8	29.5	0.785	NA	NA	NA
Vascular invasion
Yes	35	51.4	22.2
No	120	63.3	36.3	0.211	NA	NA	NA
Lymphatic metastasis
Yes	32	28.1	3.1
No	123	69.1	40.8	< 0.001	0.008	7.078	1.193-3.203
Extrahepatic metastasis
Yes	10	20	< 0.01
No	145	63.4	33.7	0.001	0.225	1.474	0.743-3.541
CK19 (n = 153)1
Yes	139	59.7	30.5
No	14	71.4	45.9	0.178	NA	NA	NA

¹Number of tumors. HBV: Hepatitis B virus; TBIL: Total bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AFP: α-fetoprotein; ALP: Alkaline phosphatase; r-GT: R-glutamyltransferase; CA 19-9: Carbohydrate antigen 19-9; CK19: Cytokeratin 19; NA: Not available.

Table 3 Univariate and multivariate analyses of prognostic factors for disease-free survival rate of intrahepatic cholangiocarcinoma patients included in this study

Factor	n	Survival rate (%)		P value		Hazard ratio	95% CI
		1-yr	3-yr	Univariate analysis	Multivariate analysis
Age (yr)
> 65	20	45	25
≤ 65	112	28.6	19.4	0.243	NA	NA	NA
Sex
Female	43	34.9	20.7
Male	89	29.2	20.1	0.679	NA	NA	NA
HBV infection
Yes	71	39.4	23.5
No	61	21.3	16.4	0.087	0.351	0.869	0.524-1.258
Cirrhosis
Yes	39	25.6	25.6
No	93	33.3	18	0.606	NA	NA	NA
Hepatolithiasis
Yes	7	14.3	< 0.01
No	135	32	21.4	0.041	0.130	2.291	0.807-5.299
Liver schistosomiasis
Yes	6	< 0.01	< 0.01
No	126	32.5	21.2	0.307	NA	NA	NA
r-GT
≤ 64 U/L	59	44.1	28.3
> 64 U/L	73	20.5	13.7	0.005	0.289	1.124	0.797-2.140
ALP
≤ 119 U/L	79	41.8	27.7
> 119 U/L	53	15.1	9.4	0.001	0.589	0.293	0.713-1.813
AFP
≤ 20 μg/L	104	34.6	21.8
> 20 μg/L	28	17.9	14.3	0.212	NA	NA	NA
CA19-9
≤ 37 U/mL	55	40	27.3
> 37 U/mL	77	24.7	15.3	0.048	0.720	0.129	0.707-1.652
Tumor number
single	115	35.7	23.2
multiple	17	< 0.01	< 0.01	< 0.001	0.011	6.515	1.194-3.863
Tumor size
< 5 cm	48	39.6	24.4
≥ 5 cm	84	26.2	17.7	0.135	NA	NA	NA
Tumor location
Left lobe	43	37.2	20.9
Right lobe	81	30.9	21.9
Both lobes	8	< 0.01	< 0.01	0.105	NA	NA	NA
Microscopic satellite lesion
Yes	34	11.8	8.8
No	98	37.8	24.2	0.002	0.017	5.736	1.106-2.745
Histological inflammation
Yes	34	47.3	20.6
No	98	25.5	20.3	0.332	NA	NA	NA
Capsule formation
Yes	14	42.9	21.4
No	118	29.7	20.1	0.683	NA	NA	NA
Tumor differentiation
Well to moderately	98	33.7	21.1
Poorly	34	23.5	17.6	0.647	NA	NA	NA
Vascular invasion
Yes	31	16.1	9.7
No	101	35.6	23.5	0.005	0.025	5.030	1.072-2.812
Lymphatic metastasis
Yes	109	4.3	< 0.01
No	23	36.7	24.5	< 0.001	0.182	1.781	0.834-2.597
Extrahepatic metastasis
Yes	8	< 0.01	< 0.01
No	124	33.1	21.6	0.059	0.609	0.261	0.551-2.764
CK19 staining (n = 130)1
Positive	13	27.4	17.9
Negative	117	61.5	34.6	0.038	0.522	0.410	0.597-2.762

¹Number of available data. AFP: α-fetoprotein; ALP: Alkaline phosphatase; r-GT: R-glutamyltransferase; CA 19-9: Carbohydrate antigen 19-9; CK19: Cytokeratin19; NA: Not available.

Table 4 Clinicopathological features of intrahepatic cholangiocarcinoma patients according to their hepatitis B virus infection

	HBV infection		P value
	Yes (n = 87)	No (n = 68)
Gender (M/F)	64/23	38/30	0.021
Age (> 65 yr) (%)	17 (19.54)	13 (14.94)	0.763
Hepatolithiasis (%)	2 (2.30)	10 (14.71)	0.004
Hepatic schistosomiasis (%)	2 (2.30)	5 (7.35)	0.133
ALT (> 42 U/L) (%)	27 (34.03)	15 (22.06)	0.212
AST (> 37 U/L) (%)	38 (43.68)	15(22.06)	0.005
TBIL (> 20 μmol/L) (%)	20 (22.99)	16 (23.53)	0.937
r-GT (> 64 U/L) (%)	49 (56.32)	38 (55.88)	0.956
ALP(> 119 U/L) (%)	33 (37.93)	33 (48.53)	0.185
AFP (> 20 μg/L) (%)	25 (28.74)	5 (7.35)	0.001
CA19-9 (> 37 U/mL) (%)	44 (50.57)	45 (66.18)	0.051
CA19-9 (> 200 U/mL) (%)	20 (22.99)	32 (47.06)	0.002
Tumor location (%)			0.520
Left lobe	28 (32.18)	27 (39.71)
Right lobe	54 (62.07)	36 (52.94)
Both lobes	5 (5.75)	5 (7.35)
Tumor size
< 5 cm	38 (43.68)	20 (29.41)	0.069
≥ 5 cm	49 (56.32)	48 (70.59)
Tumor number (%)			0.958
Single	77 (88.51)	60 (88.24)
Multiple	10 (11.49)	8 (11.76)
Histological inflammation (%)	35 (40.23)	4 (11.76)	< 0.001
Cirrhosis (%)	40 (45.98)	5 (7.35)	< 0.001
Capsule formation (%)	15 (17.24)	2 (2.41)	0.005
Tumor differentiation (%)			0.036
Well	0 (< 0.01)	5 (7.35)
Moderately	66 (75.86)	47 (69.12)
Poorly	21 (24.14)	16 (23.53)
Vascular invasion (%)	22 (25.29)	13 (19.12)	0.362
Perineural infiltration (%)	0 (< 0.01)	3 (4.41)	0.082
Microscopic satellite lesion (%)	23 (26.44)	16 (23.53)	0.679
Lymphatic metastasis (%)	12 (13.79)	20 (29.41)	0.017
Extrahepatic metastasis (%)	5 (5.75)	5 (7.35)	0.749
Immunohistochemical examinations
CK18 positive staining (%) (n = 135)1	78 (89.66)	57 (86.36)	0.531
CK19 positive staining (%) (n = 139)1	75 (86.21)	64 (96.97)	0.022

¹Number of available data. HBV: Hepatitis B virus; M: Male; F: Female; TBIL: Total bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AFP: α-fetoprotein; ALP: Alkaline phosphatase; r-GT: R-glutamyltransferase; CA19-9: Carbohydrate antigen 19-9; CK: Cytokeratin.

Table 5 Univariate and multivariate analyses of prognostic factors for survival rate of intrahepatic cholangiocarcinoma patients with hepatitis B virus infection

Factor	n	HBV infection		P value		Hazard ratio	95% CI
		1-yr (%)	3-yr (%)	Univariate analysis	Multivariate analyses
r-GT
≤ 64 U/L	38	76.3	52.1
> 64 U/L	49	69.4	34.1	0.223	NA	NA	NA
ALP
≤ 119 U/L	54	85.2	53.2
> 119 U/L	33	60.6	24.2	0.001	0.028	4.800	1.075-3.662
CA19-9
≤ 37 U/mL	43	69.8	41.0
> 37 U/mL	44	75.0	42.5	0.575	NA	NA	NA
Tumor number
single	77	75.3	44.9
multiple	10	50.0	20.0	0.066	0.058	3.599	0.972-5.587
Tumor size
< 5 cm	38	86.8	52.0
≥ 5 cm	49	61.2	33.7	0.049	0.655	0.199	0.436-1.686
Tumor location
Left lobe	28	64.3	42.9
Right lobe	54	79.6	45.5
Both lobes	5	40.0	< 0.01	0.065	0.933	0.007	0.899-1.122
Microscopic satellite lesion
Yes	23	52.2	21.7
No	64	79.7	48.8	0.001	0.001	12.066	1.648-6.014
Capsule formation
Yes	15	60.0	45.7
No	72	75.0	41.0	0.979	NA	NA	NA
Tumor differentiation
Well to moderately	66	71.2	40.3
Poorly	21	76.2	47.1	0.354	NA	NA	NA
Vascular invasion
Yes	22	50.0	17.0
No	65	80.0	50.1	0.007	0.041	4.167	1.030-4.388
Lymphatic metastasis
Yes	12	33.3	< 0.01
No	75	78.7	48.5	< 0.001	0.005	7.887	1.408-6.848
Extrahepatic metastasis
Yes	5	40.0	< 0.01
No	82	74.4	43.1	0.099	0.857	0.032	0.251-3.154

NA: Not applicable; ALP: Alkaline phosphatase; r-GT: R-glutamyltransferase; CA 19-9: Carbohydrate antigen 19-9.

Table 6 Univariate and multivariate analyses of prognostic factors for survival of intrahepatic cholangiocarcinoma patients without hepatitis B virus infection.

Factor	n	No HBV infection		P value		Hazard ratio	95% CI
		1-yr (%)	3-yr (%)	Univariate analysis	Multivariate analyses
Hepatolithiasis
Yes	10	10.0	< 0.01
No	58	51.7	24.1	0.013	0.084	2.979	0.900-5.223
r-GT
≤ 64 U/L	30	56.7	36.4
> 64 U/L	38	36.8	7.9	0.001	0.041	4.157	1.035-5.614
ALP
≤ 119 U/L	35	51.4	31.4
> 119 U/L	33	39.4	9.1	0.017	0.407	0.688	0.316-1.595
CA19-9
≤ 37 U/mL	23	60.9	43.5
> 37 U/mL	45	37.8	8.9	0.001	0.173	1.858	0.806-3.311
Tumor number
Single	60	48.3	23.2
Multiple	8	25.0	< 0.01	0.050	0.392	0.734	0.609-3.540
Tumor size
< 5 cm	20	50.0	24.0
≥ 5 cm	48	43.8	18.8	0.308	NA	NA	NA
Tumor location
Left lobe	27	40.7	21.6
Right lobe	36	55.6	22.2
Both lobes	5	< 0.01	< 0.01	0.137	NA	NA	NA
Microscopic satellite lesion
Yes	16	31.2	< 0.01
No	52	50.0	26.9	0.003	0.015	5.956	1.183-4.657
Tumor differentiation
Well to moderately	52	50.0	24.9
Poorly	16	31.2	6.2	0.076	0.016	5.844	1.172-4.569
Vascular invasion
Yes	13	53.8	30.8
No	55	43.6	18.0	0.459	NA	NA	NA
Lymphatic metastasis
Yes	20	25.0	5.0
No	48	54.2	26.9	0.015	0.430	0.624	0.683-2.452
Extrahepatic metastasis
Yes	5	< 0.01	< 0.01
No	63	49.2	22.1	< 0.001	0.065	3.403	0.933-9.940

NA: Not applicable; ALP: Alkaline phosphatase; r-GT: R-glutamyltransferase; CA 19-9: Carbohydrate antigen 19-9.