Serum liver enzymes serve as prognostic factors in patients with intrahepatic cholangiocarcinoma

Figures & data

Table 1 Clinical information for intrahepatic cholangiocarcinoma patients

Variables		N=173
Age (years)	Mean ± SD	58.83±11.31
Gender	Male	107 (38.2)
	Female	66 (61.8)
Stage	Locally advanced	36 (20.8)
	Metastatic	137 (79.2)
CA19-9	<1,000 IU/mL	109 (63.0)
	≥1,000 IU/mL	64 (37.0)
ALB level	Median (range)	40.7 (26–50.9)
GELO level	Median (range)	29.9 (20.9–55)
TP level	Median (range)	71.9 (53.3–89.3)
ALP level	Median (range)	138 (51.4–1,500)
ALT level	Median (range)	26.6 (5.0–545.30)
AST level	Median (range)	32.6 (10–366.2)
TBIL level	Median (range)	12.2 (4.3–421.3)
DBIL level	Median (range)	4.7 (0.8–322.8)
GGT level	Median (range)	113 (11–2,064)
LDH level	Median (range)	192 (74–833)

Abbreviations: ALB, albumin; ALP, alkaline phosphatase; TBIL, total bilirubin; DBIL, direct bilirubin; GGT, gamma glutamyltranspeptidase; GELO, globulin; TP, total protein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; SD, standard deviation.

Figure 1 The associations of serum liver enzymes with OS in patients with ICC.

Abbreviations: ALB, albumin; GELO, globulin; TP, total protein; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; DBIL, direct bilirubin; GGT, gamma glutamyltranspeptidase; LDH, lactate dehydrogenase; OS, overall survival; ICC, intrahepatic cholangiocarcinoma.

Table 2 Univariate analysis of prognostic factors in intrahepatic cholangiocarcinoma (N=173)

Variables	Subgroup	N	MST (month)	1-year survival rate (%)	P-value
Age (years)	<60	79	5.97	34.18	0.3345
	≥60	94	8.2	35.11
Gender	Male	107	7	32.71	0.807
	Female	66	8.75	37.88
CA19-9	<1,000 IU/mL	109	10.77	44.04	<0.0001
	≥1,000 IU/mL	64	3.8	18.75
ALB	<40.7	89	6	28.57	0.013
	≥40.7	84	8.75	36.73
GELO	<29.9	91	9.7	40.24	0.3242
	≥29.9	81	6.77	29.67
TP	<71.9	86	7.62	37.21	0.4501
	≥71.9	87	7.6	32.18
ALP	<138	86	11.6	48.84	0.001
	≥138	87	4.47	20.69
ALT	<26.6	87	7.28	33.72	0.1772
	≥26.6	86	7.76	34.48
AST	<32.6	86	9.04	36.05	0.367
	≥32.6	87	5.66	33.33
TBIL	<12.2	85	10.48	44.05	0.002
	≥12.2	88	5.54	26.14
DBIL	<4.7	86	11.93	50	<0.0001
	≥4.7	87	4	19.54
GGT	<113	85	11.86	48.24	0.001
	≥113	88	4.33	21.59
LDH	<192	87	9.01	39.53	0.087
	≥192	86	5.97	29.89
Chemotherapy	Gemcitabine-based	99	8.7	38.38	0.2284
	5-fluorouracil-based	74	7.5	22.22

Abbreviations: ALB, albumin; ALP, alkaline phosphatase; TBIL, total bilirubin; DBIL, direct bilirubin; GGT, gamma glutamyltranspeptidase; GELO, globulin; TP, total protein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; MST, median survival time.

Table 3 Association of biliary enzyme with OS in patients with intrahepatic cholangiocarcinoma (N=173)

Variables	Group	Case number	HR (95% CI)	P-value	Adjusted HR (95% CI)	Adjusted P-value
ALB	<40.7/≥40.7	84/89	0.654 (0.466–0.917)	0.014	0.741 (0.521–1.053)	0.095
ALP	<138/≥138	86/87	1.818 (1.290–2.560)	0.001	1.654 (1.170–2.337)	0.004
TBIL	<12.2/≥12.2	85/88	1.692 (1.198–2.389)	0.003	1.624 (1.142–2.310)	0.007
DBIL	<4.7/≥4.7	86/87	1.984 (1.403–2.804)	<0.0001	1.856 (1.304–2.642)	0.001
GGT	<113/≥113	85/88	1.804 (1.281–2.540)	0.001	1.641 (1.160–2.321)	0.005
Chemotherapy	5-fluorouracil-based/gemcitabine-based	74/99	1.277 (0.902–1.808)	0.148	1.290 (0.914–1.821)	0.168

Note: Analysis was adjusted for CA19-9 (<1,000 vs ≥1,000) variables identified by multivariate Cox regression analyses.

Abbreviations: OS, overall survival; HR, hazard ratio; CI, confidence interval; ALB, albumin; ALP, alkaline phosphatase; TBIL, total bilirubin; DBIL, direct bilirubin; GGT, gamma glutamyltranspeptidase.

Table 4 The effect of chemotherapies on the levels of serum liver enzyme markers in patients with intrahepatic cholangiocarcinoma (N=173)

Chemotherapy	TBIL			DBIL			ALP			GGT			ALB
	Prior	Post	P-value	Prior	Post	P-value	Prior	Post	P-value	Prior	Post	P-value	Prior	Post	P-value
Gem	12.2	17.8	0.0346	4.8	8	0.0297	137.9	169.1	0.0008	117	159	0.1487	40	36.3	<0.0001
5Fu	12.3	15.3	0.6423	4.6	6.7	0.3848	138	160.3	0.4132	109.5	125.5	0.1245	41.1	36.75	<0.0001

Abbreviations: Gem, gemcitabine; 5Fu, 5-fluorouracil; TBIL, total bilirubin; DBIL, direct bilirubin; ALP, alkaline phosphatase; GGT, gamma glutamyltranspeptidase; ALB, albumin.

Figure 2 Hazard ratios (HRs) of the serum liver enzymes were analyzed in the subgroups of patients with intrahepatic cholangiocarcinoma.

Abbreviations: ALB, albumin; ALP, alkaline phosphatase; TBIL, total bilirubin; DBIL, direct bilirubin; GGT, gamma glutamyltranspeptidase.

Figure S1 The associations between morphological tumor differences and survival were analyzed.

Abbreviation: OS, overall survival.