Correlations of health-related quality of life with serum inflammatory indicators IL-8 and mIBI in patients with hepatocellular carcinoma

Figures & data

Table 1 HRQoL instruments used in the study.

EORTC QLQ-C30	EORTC QLQ-C30 is a general cancer instrument containing multiple items, measured in multiple-point Likert scales, that reflects the multidimensionality of the HRQoL construct. It includes five functional domains (physical, role, cognitive, emotional, and social), three symptom domains (fatigue, pain, and nausea and vomiting), and a global health and HRQoL domain. Six single items assess common symptoms in cancer patients (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea), and financial problems. All scales and domains are transformed to scores ranging from 0–100. A lower score for a functional or global HRQoL scale reflects a poorer functioning level or global QoL, while a lower score for a symptom/ problem scale reflects less symptoms/problem (better HRQoL).
EORTC QLQ- HCC18	EORTC QLQ-HCC18 includes 18 multiple item scales organized into six domains (fatigue, body image, jaundice, nutrition, pain, and fever) and two items (abdominal swelling and sex life). All scales are grouped and transformed to score ranging from 0–100. A lower score represents a less severe symptom/problem (better HRQoL). EORTC QLQ-HCC18 is used together with EORTC QLQ-C30.
C30 index score	∑[(100-physical functioning), (100-role functioning), (100-emotional functioning), (100-cognitive functioning), (100-social functioning), (100-global QoL), scores of fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhea, financial difficulty] ÷ 15 Range of C30 index score: 0–100; a lower score represents a less severe symptom/problem.
HCC18 index score	∑(scores of fatigue, body image, jaundice, nutrition, pain, fever, sex life, abdominal distension) ÷ 8 Range of HCC18 index score: 0–100; a lower score represents a less severe symptom/problem.

Abbreviations: EORTC, European Organization for Research and Treatment of Cancer; HCC, Hepatocellular carcinoma; HRQoL, health-related quality of life.

Table 2 Baseline clinical and laboratory characteristics of HCC patients.

Factors	No. (%)	Median (range)
Age (years)	445	60 (18-88)
Gender
Male	395 (88.8)
Female	50 (11.2)
ECOG performance status
0	137 (30.8)
1	283 (63.6)
2	18 (4.0)
3	7 (1.6)
Baseline biochemistry
Bilirubilin μmol/L, range)		19 (3-548)
Albumin (g/L)		37 (8-53)
ALT (iu/L)		57 (12-564)
Prothrombin time (s)		12.3 (8.9-32.9)
AFP (ng/mL)		239 (1-3,637,000)
Hepatitis B, %	361 (81.1)
Hepatitis C, %	29 (6.5)
Cirrhosis, %	260 (58.4)
Ascites	111 (24.9)
Vascular Involvement	144 (32.4)
Tumor number (Single : Multiple)	165 : 280
Child-Pugh Class
A	303 (68.1)
B	125 (28.1)
C	17 (3.8)
AJCC stage
I	17 (3.8)
II	112 (23.1)
III	57 (12.9)
IV	259 (58.2)
Okuda stage
I	203 (45.6)
II	202 (45.4)
III	40 (9.0)
CUPI
Low risk	224 (50.3)
Medium risk	164 (36.9)
High risk	57 (12.8)
CUP score
0	57 (12.8)
1	86 (19.3)
2	105 (23.6)
3	96 (21.6)
4	64 (14.4)
5	34 (7.6)
6	3 (0.7)
BCLC stage
A	64 (14.4)
B	107 (24.0)
C	251 (56.4)
D	23 (5.2)
IL-8 (pg/mL)		74.8 (2.0-1670.5)
Log IL-8		1.87 (0.31-3.22)
<1.8	207 (46.5)
≥1.8	238 (53.5)
Modified inflammation-based index
0	109 (24.5)
1	127 (28.5)
2	123 (27.6)
3	86 (19.3)
C-reactive protein (mg/L)		11.13 (0.05-17.62)
≤10	199 (44.7)
>10	246 (55.3)
First-line treatment
surgical intervention	51 (11.5)
Percutaneous RFA/ethanol injection	28 (6.3)
LEM/TACE/TAE	110 (24.7)
systemic therapy	85 (19.1)
Best supportive care	171 (38.4)

Abbreviations: AFP, α-fetoprotein; AJCC, American Joint Committee on Cancer; ALT, alanine transaminase; BCLC, Barcelona clinic liver cancer; CLIP, the Cancer of the Liver Italian Program; CUPI, the Chinese University Prognostic Index; ECOG, Eastern Cooperative Oncology Group; HCC, hepatocellular carcinoma; LEM, transarterial lipiodol-ethanol mixture; RFA, radiofrequency ablation; TACE, transarterial chemoembolization; TAE, transarterial embolization.

Table 3 Health-related QoL characteristics of the 455 HCC patients based on EORTC QLQ-C30 and EORTC QLQ-HCC18 assessment

QoL variable	Mean	±SD	Median	Min.	Max.
EORTC QLQ-C30
Physical functioning	72.28	23.96	80.00	0.00	100.00
Role functioning	75.06	32.18	100.00	0.00	100.00
Emotional functioning	70.45	25.52	75.00	0.00	100.00
Social functioning	77.08	24.59	83.33	0.00	100.00
Cognitive function	68.58	30.28	66.67	0.00	100.00
Global QoL	52.53	26.38	50.00	0.00	100.00
Fatigue	42.56	29.81	33.33	0.00	100.00
Nausea/vomiting	11.01	21.28	0.00	0.00	100.00
Pain	32.10	31.55	33.33	0.00	100.00
Dyspnoea	29.74	31.27	33.33	0.00	100.00
Insomnia	40.90	35.87	33.33	0.00	100.00
Appetite loss	31.84	35.62	33.33	0.00	100.00
Constipation	16.63	26.72	0.00	0.00	100.00
Diarrhea	16.10	26.52	0.00	0.00	100.00
Financial difficulties	51.16	37.26	66.67	0.00	100.00
C30 index score	30.40	19.45	26.52	0.00	90.37
EORTC QLQ-HCC18
Fatigue	34.77	25.79	33.33	0.00	100.00
Body image	25.24	22.78	16.67	0.00	100.00
Jaundice	23.48	22.23	16.67	0.00	100.00
Nutrition	26.88	21.40	20.00	0.00	100.00
Pain	23.26	24.44	16.67	0.00	100.00
Fever	6.37	14.48	0.00	0.00	100.00
Sex life	28.31	34.40	0.00	0.00	100.00
Abdominal swelling	32.66	35.12	33.33	0.00	100.00
HCC18 index score	25.12	17.08	21.94	0.00	87.50

Abbreviations: EORTC, European Organization for Research and Treatment of Cancer; HCC, hepatocellular carcinoma; QoL, quality of life.

Figure 1 Scatter plot of C30 index scores against log IL-8 levels of the 455 HCC patients.

Abbreviation: HCC, hepatocellular carcinoma.

Figure 2 Scatter plot of HCC18 index scores against log IL-8 levels of the 455 HCC patients.

Abbreviation: HCC, hepatocellular carcinoma.

Table 4 Pearson’s correlation analyses between log IL-8 and HRQoL variables.

QoL variable	Pearson’s r	P-value
EORTC QLQ-C30
C30 Physical functioning	–0.275	<0.0001
C30 Role functioning	–0.305	<0.0001
C30 Emotional functioning	–0.096	0.043
C30 Cognitive functioning	–0.069	0.1441
C30 Social functioning	–0.244	<0.0001
C30 Global QoL	–0.25	<0.0001
C30 Fatigue	0.311	<0.0001
C30 Nausea/vomiting	0.194	<0.0001
C30 Pain	0.217	<0.0001
C30 Dyspnoea	0.177	0.0002
C30 Insomnia	0.165	0.0005
C30 Appetite loss	0.322	<0.0001
C30 Constipation	0.024	0.6186
C30 Diarrhea	0.116	0.0146
C30 Financial difficulty	0.208	<0.0001
C30 index-score	0.306	<0.0001
EORTC QLQ-HCC18
HCC18 Fatigue	0.306	<0.0001
HCC18 Body image	0.267	<0.0001
HCC18 Jaundice	0.13	0.006
HCC18 Nutrition	0.317	<0.0001
HCC18 Pain	0.164	0.0005
HCC18 Fever	0.089	0.0619
HCC18 Sex life	0.138	0.0034
HCC18 Abdominal swelling	0.29	<0.0001
HCC18 index-score	0.321	<0.0001

Abbreviations: EORTC, European Organization for Research and Treatment of Cancer; HCC, hepatocellular carcinoma; HRQoL, health-related quality of life; QoL, quality of life.

Table 5 Student’s t-test for HRQoL scores according to mIBI scores 0–1 vs 2–3.

QoL variable	mIBI 0–1	mIBI 2–3	P-value
EORTC QLQ-C30
C30 Physical functioning	80.0 (19.8)	63.6 (25.3)	<0.0001
C30 Role functioning	85.3 (25.1)	63.5 (35.3)	<0.0001
C30 Emotional functioning	71.8 (23.5)	68.9 (27.6)	0.2329
C30 Cognitive functioning	79.1 (23.7)	74.8 (25.4)	0.0658
C30 Social functioning	76.2 (26.2)	60.0 (32.2)	<0.0001
C30 Global QoL	58.9 (23.9)	45.3 (27.2)	<0.0001
C30 Fatigue	33.4 (27.4)	52.9 (29.1)	<0.0001
C30 Nausea/vomiting	6.1 (14.1)	16.6 (26.1)	<0.0001
C30 Pain	24.7 (28.5)	40.4 (32.8)	<0.0001
C30 Dyspnoea	24.6 (28.7)	35.6 (33.1)	0.0002
C30 Insomnia	35.7 (34.0)	46.7 (37.1)	0.0012
C30 Appetite loss	21.2 (30.3)	43.9 (37.4)	<0.0001
C30 Constipation	16.0 (26.7)	17.4 (26.8)	0.5753
C30 Diarrhea	13.0 (23.2)	19.6 (29.5)	0.0094
C30 Financial  difficulty	44.5 (36.3)	58.7 (37.0)	<0.0001
C30 Index-score	24.5 (16.5)	37.0 (20.4)	<0.0001
EORTC QLQ-HCC18
HCC18 Fatigue	27.1 (22.1)	43.4 (26.9)	<0.0001
HCC18 Body image	18.7 (20.2)	32.6 (23.3)	<0.0001
HCC18 Jaundice	21.8 (20.2)	25.4 (24.2)	0.0840
HCC18 Nutrition	20.6 (18.0)	34.0 (22.7)	<0.0001
HCC18 Pain	19.3 (21.9)	27.8 (26.3)	0.0003
HCC18 Fever	4.6 (12.9)	8.3 (15.9)	0.0065
HCC18 Sex life	24.7 (31.5)	32.4 (37.1)	0.0202
HCC18 swelling	22.0 (29.7)	44.7 (36.9)	<0.0001
HCC18 Index-score	19.8 (14.6)	31.1 (17.7)	<0.0001

Notes: Data are presented as mean (SD).

Abbreviations: EORTC, European Organization for Research and Treatment of Cancer; HCC, hepatocellular carcinoma; HRQoL, health-related quality of life; mIBI, modified inflammation-based index; QoL, quality of life.

Table S1 Univariate logistic regressions of HRQoL variables for log IL-8 ≥1.8

QoL variable	OR	95% CI for OR	P-value
C30 Physical functioning	0.981	0.972–0.989	<0.0001
C30 Role functioning	0.983	0.977–0.990	<0.0001
C30 Emotional functioning	0.995	0.987–1.002	0.1536
C30 Cognitive functioning	0.995	0.998–1.003	0.2292
C30 Social functioning	0.987	0.980–0.993	<0.0001
C30 Global QoL	0.982	0.974–0.989	<0.0001
C30 Fatigue	1.020	1.013–1.027	<0.0001
C30 Nausea/vomiting	1.020	1.009–1.030	0.0002
C30 Pain	1.014	1.008–1.020	<0.0001
C30 Dyspnoea	1.009	1.003–1.015	0.0054
C30 Insomnia	1.009	1.003–1.014	0.0016
C30 Appetite loss	1.017	1.011–1.023	<0.0001
C30 Constipation	1.001	0.994–1.008	0.6989
C30 Diarrhea	1.009	1.002–1.016	0.0178
C30 Financial difficulty	1.010	1.005–1.015	0.0002
C30 index-score	1.030	1.019–1.041	<0.0001
HCC18 Fatigue	1.024	1.015–1.032	<0.0001
HCC18 Body image	1.020	1.011–1.030	<0.0001
HCC18 Jaundice	1.009	1.000–1.017	0.0498
HCC18 Nutrition	1.032	1.021–1.043	<0.0001
HCC18 Pain	1.011	1.003–1.019	0.0071
HCC18 Fever	1.020	1.004–1.035	0.0107
HCC18 Sex life	1.004	0.998–1.009	0.1723
HCC18 Abdominal swelling	1.014	1.008–1.020	<0.0001
HCC18 Index-score	1.034	1.021–1.047	<0.0001

Abbreviations: HCC, hepatocellular carcinoma; HRQoL, health-related quality of life; QoL, quality of life.

Table S2 Multiple logistic regressions of HRQoL variables for log IL-8 ≥1.8

QoL variable	OR	95% CI for OR	P-value
C30 Fatigue	1.012	1.004–1.021	0.0055
C30 Appetite loss	1.011	1.004–1.019	0.0021
HCC18 Nutrition	1.022	1.008–1.035	0.0013
HCC18 Fatigue	1.013	1.002–1.023	0.0163

Abbreviations: HCC, hepatocellular carcinoma; HRQoL, health-related quality of life; QoL, quality of life.

Table S3 Univariate logistic regressions of HRQoL variables for mIBI 2–3

QoL variable	OR	95% CI for OR	P-value
C30 Physical functioning	0.969	0.960–0.978	<0.0001
C30 Role functioning	0.977	0.971–0.984	<0.0001
C30 Emotional functioning	0.996	0.988–1.003	0.2282
C30 Cognitive functioning	0.993	0.985–1.000	0.0669
C30 Social functioning	0.982	0.975–0.988	<0.0001
C30 Global QoL	0.980	0.972–0.987	<0.0001
C30 Fatigue	1.024	1.017–1.031	<0.0001
C30 Nausea/vomiting	1.027	1.016–1.038	<0.0001
C30 Pain	1.017	1.010–1.023	<0.0001
C30 Dyspnoea	1.012	1.005–1.018	0.0003
C30 Insomnia	1.009	1.003–1.014	0.0013
C30 Appetite loss	1.019	1.013–1.025	<0.0001
C30 Constipation	1.002	0.995–1.009	0.5740
C30 Diarrhea	1.010	1.002–1.017	0.0093
C30 Financial difficulty	1.011	1.005–1.016	<0.0001
C30 index-score	1.037	1.026–1.049	<0.0001
HCC18 Fatigue	1.027	1.019–1.036	<0.0001
HCC18 Body image	1.030	1.020–1.039	<0.0001
HCC18 Jaundice	1.008	0.999–1.016	0.0818
HCC18 Nutrition	1.033	1.023–1.044	<0.0001
HCC18 Pain	1.015	1.007–1.023	0.0003
HCC18 Fever	1.019	1.005–1.034	0.0080
HCC18 Sex life	1.007	1.001–1.012	0.0196
HCC18 Abdominal swelling	1.020	1.014–1.026	<0.0001
HCC18 Index-score	1.044	1.031–1.057	<0.0001

Abbreviations: HCC, hepatocellular carcinoma; HRQoL, health-related quality of life; mIBI, modified inflammation-based index; QoL, quality of life.

Table S4 Multiple logistic regressions of HRQoL variables for mIBI 2–3

QoL variable	OR	95% CI for OR	P-value
C30 Physical functioning	0.984	0.973–0.996	0.0074
C30 Role functioning	0.989	0.981–0.998	0.0150
C30 Appetite loss	1.010	1.004–1.017	0.0028
HCC18 Abdominal swelling	1.012	1.005–1.019	0.0013
HCC18 Nutrition	1.015	1.001–1.028	0.0327
HCC18 Fatigue	1.012	1.001–1.023	0.0347

Abbreviations: HCC, hepatocellular carcinoma; HRQoL, health-related quality of life; mIBI, modified inflammation-based index; QoL, quality of life.