Hepatitis B virus and hepatitis C virus play different prognostic roles in intrahepatic cholangiocarcinoma: A meta-analysis

Table 1 Main characteristics of all the studies included in the meta-analysis

Study	Study region	n	Mean age	Gender (M/F)	Clinical stage	Study design	Tumor type	Marker detection	Clinicopathological features	HR	Outcome	Quality assessment
Li et al[26], 2014	China	283	55.0 (18.0–79.0)	174/109	I-IV	Prospective	MF/PI/IG	HBsAg	NR	R	OS	8
Luo et al[27], 2014	China	1333	54.1 ± 10.9	912/421	I-IV	Retrospective	MF	HBsAg/anti-HCV	NR	R	OS	9
Uenishi et al[28], 2014	Japan	90	NR	61/29	I-IV	Retrospective	MF	HBsAg/anti-HCV	G	R	OS	9
Zhang et al[29], 2014	China	127	55.5 ± 11.8	102/25	I-IV	Retrospective	MF/PI/IG	HBsAg/anti-HCV	NR	R	OS/DFS	9
Liu et al[30], 2013	China	81	59.0 (30.0-76.0)	48/33	NR	Retrospective	MF/PI/IG	HBsAg/HBcAb	NR	R	OS	9
Wu et al[31], 2013	China	138	55	107/31	I-IV	Retrospective	MF/PI/IG	HBsAg/HBcAb	G, ALT, AST, TB, γ-GT, AFP, CA19-9, C, CF, D, TN, TS, LNM, VI	E	OS	8
Jiang et al[32], 2011	China	76	51.0 (40.0–60.0)	53/23	I-IV	Retrospective	MF/PI/IG	HBsAg	NR	R	OS	9
Peng et al[33], 2011	China	62	NR	NR	NR	Retrospective	MF/PI/IG	HBsAg/HBcAb	AFP, CA19-9, C, CF, D, TL, TN, TS, LNM, VI	NR	NR	8
Uenishi et al[34], 2011	Japan	35	61.0 (35.0-83.0)	11/24	II-IV	Retrospective	MF	HBsAg/anti-HCV	NR	E	OS	8
Zhou et al[11], 2011	China	155	55.0 ± 10.7 (27.0-76.0)	102/53	NR	Retrospective	MF/PI/IG	HBsAg	G, ALT, AST, TB, γ-GT, AFP, CA19-9, C, CF, D, TL, TN, TS, LNM, VI	R	OS/DFS	9
Zhang et al[12], 2010	China	40	56.0 (34.0-74.0)	24/16	I-IV	Retrospective	MF/PI/IG	HBsAg/HBcAb	NR	E	OS	8
Zhou et al[10], 2010	China	317	53.1 ± 10.5	223/94	NR	Retrospective	MF/PI/IG	HBsAg	G, ALT, AST, TB, γ-GT, AFP, CA19-9, C, CF, D, TL, TN, LNM, VI	NR	NR	8
Hai et al[13], 2005	Japan	38	NR	23/15	I-IV	Retrospective	MF/PI/IG	anti-HCV	G	E	OS	8
Asayama et al[35], 2002	Japan	67	62.0 (33.0-83.0)	36/31	NR	Retrospective	MF/PI/IG	HBsAg/anti-HCV	G	E	OS	8

n: Number of patients; M: Male; F: Female; HR: Hazard ration; R: Reported; NR: Not reported; E: Estimated; OS: Overall survival; DFS: Disease-free survival; MF: Mass-forming; PI: Periductal infiltrating; IG: Intraductal growth; G: Gender; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TB: Total bilirubin; γ-GT: γ-glutamyl transpeptidase; AFP: Alpha fetoprotein; CA19-9: Carbohydrate antigen 19-9; C: Cirrhosis; CF: Capsule formation; D: Differentiation; TL: Tumor location; TN: Tumor number; TS: Tumor size; LNM: Lymph node metastasis; VI: Vascular invasion.

Table 2 Subgroup meta-analysis for the correlation between hepatitis B virus infection and overall survival

Subgroup	n	Analytical model	HR	95%CI	Heterogeneity
					I2(%)	P value
Sample size
Sample size ≥ 100	5	FEM	0.72	0.65-0.81	33.3	0.200
Sample size < 100	6	FEM	0.84	0.72-0.98	28.7	0.219
Tumor type
MF, PI or IG	8	REM	0.75	0.62-0.90	51.8	0.043
MF only	3	FEM	0.74	0.64-0.85	0.00	0.709
Study region
China	8	FEM	0.75	0.69-0.82	40.7	0.107
Non-China	3	FEM	1.10	0.67-1.80	0.00	0.476
Mean age
Mean age ≥ 55	8	FEM	0.71	0.62-0.82	37.6	0.130
Mean age < 55	2	REM	0.80	0.67-0.95	59.7	0.115

FEM: Fixed-effects model; REM: Random-effects model; HR: Hazard ration; CI: Confidence interval; MF: Mass-forming; PI: Periductal infiltrating; IG: Intraductal growth.

Table 3 Meta-analysis of hepatitis B virus infection and clinicopathological features

Clinicopathological features	n	Cases	Analytical model	OR	95%CI	Heterogeneity
						I2(%)	P value
Gender (male vs female)	4	677	REM	1.91	1.06-3.44	55.0	0.084
ALT (≥ 42 U/L vs < 42 U/L)	3	610	REM	1.23	0.64-2.35	63.3	0.066
AST (≥ 37 U/L vs < 37 U/L)	3	610	REM	1.93	1.11-3.35	52.8	0.120
TBIL(≥ 20 μmol/L vs < 20 μmol/L)	3	610	FEM	0.91	0.62-1.33	0.00	0.979
γ-GT (≥ 64 U/L vs < 64 U/L)	3	610	REM	0.77	0.43-1.38	61.7	0.074
AFP (≥ 20 ng/mL vs < 20 ng/mL)	4	669	FEM	3.86	2.58-5.78	0.00	0.804
CA19-9 (≥ 37 U/mL vs < 37 U/mL)	4	668	FEM	0.47	0.34-0.65	0.00	0.806
Cirrhosis (yes vs no)	4	672	FEM	6.44	4.33-9.56	38.8	0.179
Capsule formation (yes vs no)	4	672	FEM	6.04	3.56-10.26	31.9	0.221
Differentiation (well/moderate vs poor)	4	672	REM	0.86	0.41-1.80	73.5	0.010
Tumor location (both lobes vs one lobe)	3	534	FEM	0.76	0.31-1.87	0.00	0.995
Tumor number (multiple vs single)	4	672	FEM	0.91	0.57-1.46	0.00	0.983
Tumor size (≥ 5 cm vs < 5 cm)	3	355	FEM	0.72	0.46-1.14	37.9	0.200
Lymph node metastasis (yes vs no)	4	672	FEM	0.39	0.25-0.58	0.00	0.990
Vascular invasion(yes vs no)	4	672	REM	1.10	0.49-2.43	69.0	0.021

FEM: Fixed-effects model; REM: Random-effects model; OR: Odds ratio; CI: Confidence interval; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; γ-GT: γ-glutamyl transpeptidase; AFP: Alpha fetoprotein; CA19-9: Carbohydrate antigen 19-9.