J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 10, Number 10, October 2018, pages 765-771

Number of Nodules but not Size of Hepatocellular Carcinoma Can Predict Refractoriness to Transarterial Chemoembolization and Poor Prognosis

Figure 1. Estimates of cumulative survival rates according to response to TACE (Kaplan-Meier method). There was a significant difference in cumulative survival (P < 0.001, log-rank test) between Response P patients and Response NP patients.

Figure 2. Receiver operating characteristic curves for response grades and pre-TACE tumor numbers (Response P vs. NP). The AUC value was high (0.877). The cut-off value was 7.5.

Figure 3. Estimates of cumulative survival rates according to pre-treatment tumor number (Kaplan-Meier method). There was a significant difference in cumulative survival (P < 0.001, log-rank test) between patients with a tumor number > 8 and those with a tumor number ≤ 7. N represents the number of tumor nodules.

**Table 1.** Patient Characteristics
Item	Data
Values are expressed as mean ± SD. The range of numbers is shown in parenthesis. Child-Pugh score was not assessed in two patients due to missing data. Numbers of tumors ≥ 11 are expressed as 11. **Values of PIVKA-II < 30 are expressed as 0. B: hepatitis B virus; C: hepatitis C virus; NBNC: non-B non-C; Al: alcohol; AFP: alfa-feto protein; PIVKA-II: protein induced by vitamin K absence or antagonist-II.
Age (years)	71.6 ± 6.6
Sex (male/female)	41/9
Etiology (B/C/NBNC/Al)	10/31/4/5
Total bilirubin (mg/dL)	0.91 ± 0.33
Prothrombin time (%)	86.5 ± 10.2
Albumin (g/dL)	3.83 ± 0.0.35
Platelets (× 10⁴/µL)	12.5 ± 5.6
Child-Pugh classification (A/B/C)	45/3/0*
Number of tumor nodules**	4.5 ± 3.6
Max size of tumor (mm)	31.3 ± 23.0 (10 - 135)
Up-to-7 criteria (in/out)	28/22
AFP (ng/mL)	1,745.6 ± 11,253.1 (2 - 78,845)
PIVKA-II (mAU/mL)	2,331.4 ± 10,923.1 (0*** - 75,000)

Table 1. Patient Characteristics

Item

Data

Values are expressed as mean ± SD. The range of numbers is shown in parenthesis. *Child-Pugh score was not assessed in two patients due to missing data. **Numbers of tumors ≥ 11 are expressed as 11. ***Values of PIVKA-II < 30 are expressed as 0. B: hepatitis B virus; C: hepatitis C virus; NBNC: non-B non-C; Al: alcohol; AFP: alfa-feto protein; PIVKA-II: protein induced by vitamin K absence or antagonist-II.

Age (years)

71.6 ± 6.6

Sex (male/female)

41/9

Etiology (B/C/NBNC/Al)

10/31/4/5

Total bilirubin (mg/dL)

0.91 ± 0.33

Prothrombin time (%)

86.5 ± 10.2

Albumin (g/dL)

3.83 ± 0.0.35

Platelets (× 10⁴/µL)

12.5 ± 5.6

Child-Pugh classification (A/B/C)

45/3/0*

Number of tumor nodules**

4.5 ± 3.6

Max size of tumor (mm)

31.3 ± 23.0 (10 - 135)

Up-to-7 criteria (in/out)

28/22

AFP (ng/mL)

1,745.6 ± 11,253.1 (2 - 78,845)

PIVKA-II (mAU/mL)

2,331.4 ± 10,923.1 (0*** - 75,000)

**Table 2.** Univariate and Multivariate Analyses to Investigate Factors Predicting Response P Versus NP
	Univariate	Multivariate
HR: hazard ratio; M: male; F: female; C: hepatitis C virus; AFP: alfa-feto protein; PIVKA-II: protein induced by vitamin K absence-II.
Age (years)	1.060	0.998 - 1.127	0.059
Sex (M vs. F)	0.997	0.309 - 3.214	0.996
Etiology (C vs. others)	0.979	0.426 - 2.249	0.960
Total bilirubin (mg/dL)	4.166	1.396 - 12.432	0.011
Prothrombin time (%)	0.965	0.927 - 1.004	0.080
Albumin (g/dL)	0.629	0.248 - 1.596	0.329
Platelets (× 10⁴/µL)	0.889	0.808 - 0.978	0.016
AFP (≥ 10 vs. < 10)	2.202	0.878 - 5.521	0.092
PIVKA-II (≥ 75 vs. < 75)	3.252	1.366 - 7.739	0.008	4.539	1.214 - 16.966	0.025
Tumor number	1.590	1.365 - 1.854	0.000	1.475	1.245 - 1.747	0.000
Tumor size	0.997	0.977 - 1.019	0.811
Up to 7 (in vs. out)	0.098	0.036 - 0.266	0.000
Past TACE number	1.711	1.333 - 2.194	0.000	1.472	1.058 - 2.048	0.022

Table 2. Univariate and Multivariate Analyses to Investigate Factors Predicting Response P Versus NP

Univariate

Multivariate

95% CI

HR: hazard ratio; M: male; F: female; C: hepatitis C virus; AFP: alfa-feto protein; PIVKA-II: protein induced by vitamin K absence-II.

Age (years)

1.060

0.998 - 1.127

0.059

Sex (M vs. F)

0.997

0.309 - 3.214

0.996

Etiology (C vs. others)

0.979

0.426 - 2.249

0.960

Total bilirubin (mg/dL)

4.166

1.396 - 12.432

0.011

Prothrombin time (%)

0.965

0.927 - 1.004

0.080

Albumin (g/dL)

0.629

0.248 - 1.596

0.329

Platelets (× 10⁴/µL)

0.889

0.808 - 0.978

0.016

AFP (≥ 10 vs. < 10)

2.202

0.878 - 5.521

0.092

PIVKA-II (≥ 75 vs. < 75)

3.252

1.366 - 7.739

0.008

4.539

1.214 - 16.966

0.025

Tumor number

1.590

1.365 - 1.854

0.000

1.475

1.245 - 1.747

0.000

Tumor size

0.997

0.977 - 1.019

0.811

Up to 7 (in vs. out)

0.098

0.036 - 0.266

0.000

Past TACE number

1.711

1.333 - 2.194

0.000

1.472

1.058 - 2.048

0.022

**Table 3.** Univariate and Multivariate Analyses to Investigate Factors Associated With Post-TACE Survival
	Univariate	Multivariate
HR: hazard ratio; M: male; F: female; C: hepatitis C virus; AFP: alfa-feto protein; PIVKA-II: protein induced by vitamin K absence-II.
Age (years)	1.031	0.976 - 1.089	0.276
Sex (M vs. F)	0.629	0.515 - 2.998	0.629
Etiology (C vs. others)	0.921	0.468 - 1.815	0.813
Total bilirubin (mg/dL)	6.842	2.080 - 22.510	0.002
Prothrombin time (%)	0.995	0.922 - 0.989	0.010
Albumin (g/dL)	0.352	0.265 - 1.032	0.059
Platelets (×104/µL)	0.871	0.798 - 0.951	0.002	0.876	0.803 - 0.955	0.003
AFP (≥ 10 vs. < 10)	1.669	0.773 - 3.606	0.192
PIVKA-II (≥ 75 vs. < 75)	1.716	0.843 - 3.497	0.137
Tumor number	1.307	1.174 - 1.456	0.000	1.330	1.178-1.501	0.000
Tumor size	1.003	0.987 - 1.019	0.734
Up to 7 (in vs. out)	0.296	0.150 - 0.588	0.000
Past TACE number	1.103	0.907 - 1.341	0.327

Table 3. Univariate and Multivariate Analyses to Investigate Factors Associated With Post-TACE Survival

Univariate

Multivariate

95% CI

HR: hazard ratio; M: male; F: female; C: hepatitis C virus; AFP: alfa-feto protein; PIVKA-II: protein induced by vitamin K absence-II.

Age (years)

1.031

0.976 - 1.089

0.276

Sex (M vs. F)

0.629

0.515 - 2.998

0.629

Etiology (C vs. others)

0.921

0.468 - 1.815

0.813

Total bilirubin (mg/dL)

6.842

2.080 - 22.510

0.002

Prothrombin time (%)

0.995

0.922 - 0.989

0.010

Albumin (g/dL)

0.352

0.265 - 1.032

0.059

Platelets (×104/µL)

0.871

0.798 - 0.951

0.002

0.876

0.803 - 0.955

0.003

AFP (≥ 10 vs. < 10)

1.669

0.773 - 3.606

0.192

PIVKA-II (≥ 75 vs. < 75)

1.716

0.843 - 3.497

0.137

Tumor number

1.307

1.174 - 1.456

0.000

1.330

1.178-1.501

0.000

Tumor size

1.003

0.987 - 1.019

0.734

Up to 7 (in vs. out)

0.296

0.150 - 0.588

0.000

Past TACE number

1.103

0.907 - 1.341

0.327