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 12, Number 1, January 2020, pages 26-35

Prognostic Factors for Patients With a Large Number of Hepatocellular Carcinoma Nodules

Figure 1. Kaplan-Meier analysis of cumulative OS of the 46 HCC patients with 30 nodules or more. OS: overall survival; HCC: hepatocellular carcinoma.

Figure 2. Kaplan-Meier analysis of cumulative OS of the 46 HCC patients with 30 nodules or more in relation to (a) sex, (b) tumor number, (c) initial treatment (TACE or not), (d) total bilirubin and (e) prothrombin time. OS: overall survival; HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization.

Figure 3. Subsequent treatment course of the 39 patients who underwent TACE as an initial treatment. The solid line denotes the survival time of patients, and the crosses denote deaths. The open circles and open triangles denote TACE and TAI treatments. The open boxes denote sorafenib administration. Patients who received sorafenib are shown in the lower part, whereas patients who did not are shown in the upper part. TACE: transarterial chemoembolization; TAI: transarterial infusion chemotherapy.

Figure 4. Kaplan-Meier analysis of cumulative OS of the 39 HCC patients who underwent TACE as an initial treatment in relation to the presence or absence of (a) repeated TACE as the after-treatment, (b) the TAI as the after-treatment and (c) the administration of sorafenib. OS: overall survival; HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; TAI: transarterial infusion chemotherapy.

**Table 1.** Previous Treatment, Initial Treatment and After Treatment of the 46 HCC Patients With 30 Nodules or More
Content of therapy	No. (%)
HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; TAI: transarterial infusion chemotherapy; RFA: radiofrequency ablation; PEI: percutaneous ethanol injection.
Previous treatment
Any	43 (93%)
TACE	38 (83%)
TAI	3 (7%)
RFA	22 (48%)
PEI	13 (28%)
Hepatic resection	14 (30%)
Initial treatment
Any	46 (100%)
TACE	39 (85%)
TAI	7 (15%)
Sorafenib	1 (2%)
After treatment
Any	35 (76%)
TACE	26 (57%)
TAI	17 (37%)
Sorafenib	11 (24%)

Table 1. Previous Treatment, Initial Treatment and After Treatment of the 46 HCC Patients With 30 Nodules or More

Content of therapy

No. (%)

HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; TAI: transarterial infusion chemotherapy; RFA: radiofrequency ablation; PEI: percutaneous ethanol injection.

Previous treatment

Any

43 (93%)

TACE

38 (83%)

TAI

3 (7%)

RFA

22 (48%)

PEI

13 (28%)

Hepatic resection

14 (30%)

Initial treatment

Any

46 (100%)

TACE

39 (85%)

TAI

7 (15%)

Sorafenib

1 (2%)

After treatment

Any

35 (76%)

TACE

26 (57%)

TAI

17 (37%)

Sorafenib

11 (24%)

**Table 2.** Univariate and Multivariate Analyses to Investigate Factors Contributing to Overall Survival in HCC Patients With 30 Nodules or More
Clinical characteristics	Univariate analysis	Multivariate analysis
Significant factors (P < 0.05) in univariate analysis (gender, total bilirubin, albumin, prothrombin time, number of tumor and initial therapy) and age were used in the multivariate analysis. HCC: hepatocellular carcinoma; HR: hazards ratio; CI: confidence interval; ALT: alanine aminotransferase; AFP: alpha-fetoprotein; DCP: des-gamma-carboxy prothrombin; TACE: transarterial chemoembolization.
Age (/1 year increment)	0.991	0.949 - 1.034	0.679	1.015	0.966 - 1.066	0.558
Gender (male)	0.467	0.240 - 0.908	0.025	0.283	0.130 - 0.617	0.002
Hepatitis C	0.549	0.248 - 1.215	0.139
Hepatitis B	1.291	0.488 - 3.419	0.607
Alcohol (< 60 mg/day)	1.505	0.532 - 4.256	0.441
Child-Pugh classification (A)	0.561	0.274 - 1.149	0.114
ALT (/1 U/L increment)	0.992	0.976 - 1.009	0.351
Total bilirubin (/1 mg/dL increment)	2.714	1.185 - 6.217	0.018	4.178	1.394 - 12.518	0.011
Albumin (/1 g/dL increment)	0.304	0.144 - 0.642	0.002	0.877	0.307 - 2.502	0.806
Prothrombin time (/1% increment)	0.965	0.940 - 0.991	0.009	0.959	0.920 - 1.000	0.049
AFP (< 100 ng/mL)	0.705	0.368 - 1.350	0.292
DCP (< 200 mAU/mL)	0.772	0.401 - 1.488	0.440
Maximum diameter of tumor (< 30 mm)	0.738	0.381 - 1.429	0.367
Number of tumor (30 - 59 nodules)	0.378	0.187 - 0.763	0.007	0.284	0.130 - 0.613	0.002
Initial therapy (TACE)	0.291	0.071 - 0.762	0.012	0.301	0.104 - 0.890	0.027

Table 2. Univariate and Multivariate Analyses to Investigate Factors Contributing to Overall Survival in HCC Patients With 30 Nodules or More

Clinical characteristics

Univariate analysis

Multivariate analysis

95% CI

P value

95% CI

P value

Significant factors (P < 0.05) in univariate analysis (gender, total bilirubin, albumin, prothrombin time, number of tumor and initial therapy) and age were used in the multivariate analysis. HCC: hepatocellular carcinoma; HR: hazards ratio; CI: confidence interval; ALT: alanine aminotransferase; AFP: alpha-fetoprotein; DCP: des-gamma-carboxy prothrombin; TACE: transarterial chemoembolization.

Age (/1 year increment)

0.991

0.949 - 1.034

0.679

1.015

0.966 - 1.066

0.558

Gender (male)

0.467

0.240 - 0.908

0.025

0.283

0.130 - 0.617

0.002

Hepatitis C

0.549

0.248 - 1.215

0.139

Hepatitis B

1.291

0.488 - 3.419

0.607

Alcohol (< 60 mg/day)

1.505

0.532 - 4.256

0.441

Child-Pugh classification (A)

0.561

0.274 - 1.149

0.114

ALT (/1 U/L increment)

0.992

0.976 - 1.009

0.351

Total bilirubin (/1 mg/dL increment)

2.714

1.185 - 6.217

0.018

4.178

1.394 - 12.518

0.011

Albumin (/1 g/dL increment)

0.304

0.144 - 0.642

0.002

0.877

0.307 - 2.502

0.806

Prothrombin time (/1% increment)

0.965

0.940 - 0.991

0.009

0.959

0.920 - 1.000

0.049

AFP (< 100 ng/mL)

0.705

0.368 - 1.350

0.292

DCP (< 200 mAU/mL)

0.772

0.401 - 1.488

0.440

Maximum diameter of tumor (< 30 mm)

0.738

0.381 - 1.429

0.367

Number of tumor (30 - 59 nodules)

0.378

0.187 - 0.763

0.007

0.284

0.130 - 0.613

0.002

Initial therapy (TACE)

0.291

0.071 - 0.762

0.012

0.301

0.104 - 0.890

0.027

**Table 3.** The P Values in the Difference of the Cumulative Overall Survival Rate in HCC Patients With 30 Nodules or More Undergoing TACE as Initial Treatment Between Patients With and Without Subsequent Sorafenib Administration in Various Patient Subgroups
Patient subgroup	Median survival time (months) (95% CI)	P value^a
^aP values in the difference of the cumulative overall survival between patients with and without subsequent sorafenib administration were determined by the generalized Wilcoxon test. HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; CI: confidence interval; TAI: transarterial infusion chemotherapy.
All (n = 39)	22.5 (13.6 - 31.5)	12.1 (3.19 - 21.0)	0.026
Survival of > 6 months (n = 32)	22.5 (13.6 - 31.5)	15.4 (11.9 - 19.0)	0.100
Subsequent TACE or TAI at least once (n = 30)	22.5 (13.6 - 31.5)	15.4 (12.1 - 18.8)	0.098
Survival of > 6 months and subsequent TACE or TAI > 2 or more (n = 18)	23.7 (20.8 - 26.6)	15.4 (12.8 - 18.1)	0.033

Table 3. The P Values in the Difference of the Cumulative Overall Survival Rate in HCC Patients With 30 Nodules or More Undergoing TACE as Initial Treatment Between Patients With and Without Subsequent Sorafenib Administration in Various Patient Subgroups

Patient subgroup

Median survival time (months) (95% CI)

P value^a

Patients with subsequent sorafenib administration (n = 29)

Patients without subsequent sorafenib administration (n = 10)

^aP values in the difference of the cumulative overall survival between patients with and without subsequent sorafenib administration were determined by the generalized Wilcoxon test. HCC: hepatocellular carcinoma; TACE: transarterial chemoembolization; CI: confidence interval; TAI: transarterial infusion chemotherapy.

All (n = 39)

22.5 (13.6 - 31.5)

12.1 (3.19 - 21.0)

0.026

Survival of > 6 months (n = 32)

22.5 (13.6 - 31.5)

15.4 (11.9 - 19.0)

0.100

Subsequent TACE or TAI at least once (n = 30)

22.5 (13.6 - 31.5)

15.4 (12.1 - 18.8)

0.098

Survival of > 6 months and subsequent TACE or TAI > 2 or more (n = 18)

23.7 (20.8 - 26.6)

15.4 (12.8 - 18.1)

0.033