Assessment of KL-6 as a tumor marker in patients with hepatocellular carcinoma

Table 1 Background data of the study groups

	Egyptian			Japanese
	HCC (+)	HCC (–)	P	HCC (+)	HCC (–)	P
	n = 65	n = 106		n = 45	n = 128
Mean age (SD, yr)	57±11b	47±9	<0.001	66±10b	63±10	NS
Age <50 yr	16 (25)d	65 (61)	<0.001	3 (7)d	17 (13)	NS
Male	50 (77)	82 (77)	NS	38 (84)	87 (68)	0.024
Liver disease
Viral	61 (94)	96 (91)		44 (98)	107 (84)
HCV-related	59 (91)	92 (87)	NS	36 (80)	81 (63)	0.031
HBV-related	2 (3)1	4 (4)	NS	8 (18)1	28 (22)	NS
Non-viral	4 (6)	10 (9)	NS	1 (2)	20 (16)	0.010
Cirrhosis	46 (71)	45 (42)	<0.001	40 (89)	40 (31)	<0.001
Child’s C	25 (38)f	17 (16)	0.001	4 (9)f	1 (1)	0.017
Mean±(SD)
ALT (IU/L)	73±95	66±45	0.08	55±35	50±39	NS
Serum Albumin (g/L)	3.0±0.7	3.0±0.5	NS	3.6 ±0.5	4.2±0.4	<0.001
Platelet count×1 000/mL3	186±107h	89±53	0.001	130±51h	170±71	<0.001
AFP >10 ng/mL (+)	64 (99)	28 (26)	<0.001	30 (67)	23 (18)	<0.001
PIVIKA>40 mAU/L (+)	51 (79)	38 (36)	<0.001	16 (36)	27 (21)	0.047

^bP<0.001,

^dP<0.001,

^fP<0.001,

^hP<0.001 vs Japannese,

¹P = 0.001.

Table 2 Comparison of background tumor characteristics between Egyptian and Japanese HCC patients

Tumor characteristic	Egyptian	Japanese	P
	(n = 65)	(n = 45)
Tumor multiplicity
Solitary	25 (38)	22 (49)	>0.2
Multiple	40 (62)	23 (51)	0.06
Tumor size
<3 cm	32 (49)	20 (44)	>0.2
3:< 5cm	15 (23)	14 (31)	>0.2
≥5 cm	18 (28)	11 (25)	0.13
Metastases	01 (2) >0.2
Tumor grade1
Well differentiated	5 (16)	2 (8)	>0.2
Poorly differentiated	5 (16)	4 (16)	>0.2

¹Tumor grade is analyzed in 32 of the Egyptian and 22 of the Japanese groups who passed HCC resection operation during the study period.

Table 3 Comparison of the result of different tumor markers between HCC and non-HCC group

Tumor marker (cut-off point)	Sensitivity	Specificity
	%	%
AFP (10 ng/mL)	86	78
PIVKA-II (35 mAU/L)	61	72
KL-6 (500 U/L)	34	80
AFP+PIVKA-II	861	93
AFP+KL-6	872	94
AFP+PIVKA-II+KL-6	87	99

¹All PIVKA-II (+) HCC patients are AFP (+).

²One KL-6 (+) HCC patient is AFP (–).

Table 4 Factors associated with KL-6 positivity in the study population

Factors	Total	KL-6 (+)	KL-6 (–)
Age (yr)
>=50	244	60 (24)	184 (75)
<50	100	24(24)	76 (76)
P	NS
Sex
Male	257	61 (24)	196 (76)
Female	87	23 (26)	64 (73)
P	NS
Ethnicity
Egyptian	171	53 (31)	118 (69)
Japanese	173	31 (18)	142 (82)
P	0.003
Underlying liver
disease
HCV-related	267	71 (27)	196 (73)
HBV-related	42	5 (12)	37 (88)
Non-viral	35	8 (23)	27 (77)
P	NS
Cirrhosis
(+)	169	46 (27)	123 (73)
(–)	175	38 (22)	137 (78)
P	NS
Child’s class
C	47	20 (43)	27 (57)
A&B	297	64 (21)	233 (78)
P	0.002
HCC:
(+)	110	37 (34)	73 (66)
(–)	234	47 (20)	187 (80)
P	0.008
AFP
(+)	145	49 (34)	96 (66)
(–)	199	35 (17)	164 (82)
P	<0.001

Table 5 Comparison of the clinical profile of KL-6 positive and negative patients with and without HCC

	HCC (+)			HCC (–)
	KL-6 (+)	KL-6 (–)	P	KL-6 (+)	KL-6 (–)	P
	n = 37	n = 73		n = 47	n = 187
Mean age (yr)1	59±12	62±10	NS	57±12	56±13	NS
Cirrhosis	39 (81)	55 (76)	NS	16 (34)	65 (35)	NS
Child’s C	13 (35)	15 (21)	NS	7 (15)	11 (6)	0.045
Mean ALT	74±101	62±61	NS	59±33	57±45	NS
Serum
Albumin (g/L)1	2.9±0.7	3.3±0.7	0.029	3.5±0.9	3.8±0.8	0.041
Bilirubin (mmol/L)1	2.7±2.8	2.5±3.0	0.077	2.4±2.9	1.4±1.9	0.023
ALP (IU/L)1	564±475	505±469	0.021	316±139	299±152	NS
AFP (+)	36 (97)	58 (80)	0.013	13 (28)	37 (20)	NS
PIVIKA (+)	23 (62)	44 (60)	NS	14 (30)	50 (27)	NS

¹Data is shown as mean±SD. Other data is shown as n (%).

Table 6 Comparison of mean serum KL-6 level among different study sub-groups

	Egyptian			Japanese
	HCC (+)	HCC (-)	P	HCC (+)	HCC (-)	P
Chronic liver disease1:	576 (522)	398 (185)	0.001	510 (300)	350 (147)	<0.001
HCV-related	558 (524)	400 (172)	0.008	356 (290)	382 (209)	>0.2
HBV-related	778 (663)	246 (72)	>0.2	877 (292)	340 (163)	<0.001
Non-viral	729 (538)	446 (309)	>0.2	2622 ()	357 (160)	–
Cirrhotics	599 (586)	406 (159)	0.035	510 (350)	374 (196)	0.035
Non-cirrhotics	518 (325)	398 (185)	0.045	225 (73)	349 (222)	<0.001

¹The KL-6 values are shown as mean (SD) U/L.

²Only one patient’s data.

Table 7 Difference in mean KL-6 level according to HCC size

	Egyptian	P1value	Japanese	P value
	(n = 65)		(n = 45)
Tumor size
<3 cm	485±227		618±361
3:<5 cm	643±685	>0.1	456±285	0.17
≥5 cm	581±420	>0.1	371±168	0.04

¹P value is shown for the difference group (<3 cm) and the other two groups.