Value of quality of life analysis in liver cancer: A clinician’s perspective

Table 1 Health related quality of life instruments commonly used in hepatocellular carcinoma studies

General instruments
European Organization for Research and Treatment of Cancer QLQ-C30	EORTC QLQ-C30 is a general cancer instrument containing multiple items, measured in multiple-point Likert scales, that reflect the multidimensionality of HRQOL construct[15]. It includes five functional domains (physical, role, cognitive, emotional and social), three symptom domains (fatigue, pain, nausea/vomiting), and a global health and QOL domain. Six single items assess common symptoms in cancer patients (dyspnea, appetite loss, sleep disturbance, constipation and diarrhea) and financial problem. All scales and domains are transformed to scores ranging from 0 to 100. A lower score for a functional or global QOL scale reflects a relatively poorer functioning level or global QOL, a higher score for a symptom/problem scale reflects a more disturbing symptom/problem
Functional Assessment of Cancer Therapy - General	The FACT-G questionnaire is a commonly used tool for HRQOL assessment in general cancer patients[16]. It consists of 27 items for assessment of symptoms and four domains of HRQOL: (1) physical well being (PWB) containing seven items with a subscale score ranging from 0 to 28 points; (2) socio-family well being (SFWB) containing seven items with a subscale score of 0-28 points; (3) emotional well being (EWB) containing six items with a subscale score of 0-24 points; and (4) functional well being (FWB) containing seven items with a subscale score of 0-28 points. Patients were asked to score each item according to how true each statement was to them during the past week on a 5-point ordinal scale, from 0 indicating “not at all” to 4 indicating “very much”. The FACT-G total score is the summation of the four subscales (PWB, FWB, SFWB and EWB) scores and can range from 0 to 108. Higher scores reflect better HRQOL
Spitzer Quality of Life Index (Spitzer QoL index)	Spitzer QoL index is a general cancer HRQOL measurement[17]. A score of 0 (worst QOL) to 10 (best QoL) was calculated after the patient answered five items of the questionnaire in the areas of activity, daily life, health perceptions, social support and behavior. Each item is rated on a 3-point Likert scale
Short form 36	SF-36 is a general disease questionnaire to measure the following 8 domains of health: General health, bodily pain, social functioning, role-physical, physical functioning, vitality, role-emotional and mental health[18]. The raw scores of each subscale are converted to scores that range from 0 to 100, with higher scores indicating higher levels of functioning or well being. Scores representing overall physical functioning and mental functioning were calculated from the subscales and are grouped as the physical component summary scale and mental component summary scale
Short form 12	SF-12 is a shortened version of SF-36. It contains a 12-item generic measure of health status developed from SF-36[19]. It also yields scores for eight domains: Physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. It likewise provides overall summaries of the physical and mental components
World Health Organization Quality of Life Assessment 100	The WHOQOL-100 questionnaire comprises of 100 items grouped into 25 facets[20]. One of the facets measures overall quality of life/health. The remaining 24 facets are organized in 6 domains: (1) physical health; (2) psychological health; (3) level of independence; (4) social relationships; (5) environment; and (6) spirituality/religion/personal beliefs. Each facet includes four items, rated on a 5-point Likert scale, with higher scores indicating more positive evaluations. Domain and facet raw scores can also be transformed onto a 0 to 100 scale. Higher scores denote higher HRQOL
World Health Organization Quality of Life Assessment abbreviated version	The original 6-domain structure of WHOQOL-100 was subsequently reduced into 4 comprehensive domains by the WHOQOL Group, comprising: (1) physical health (merging the level of independence domain); (2) psychological health (merging the spirituality/religion/personal beliefs domain); (3) social relationships; and (4) environment[21]. It contains a total of 26 questions. Attributes incorporated within the physical health domain of the WHOQOL-BREF include: activities of daily living, dependence on medicines or medical aids, energy and fatigue, mobility, pain and discomfort, sleep and rest and work capacity. Attributes incorporated within the psychological health domain are: body image and appearance, negative and positive feelings, self-esteem, spirituality, religion and personal beliefs, thinking, learning, memory and concentration. Measurements of social health domain include personal relationships, social support and sexual activity. Features incorporated in the environmental health domain are: Financial resources, freedom, physical safety and security, health and social care, home environment, opportunities for acquiring the new information and skills, participation in and opportunities for recreation, physical environment and transportation. Higher scores denote higher HRQOL
EuroQoL-5D	EQ-5D is a general disease instrument for describing and valuing HRQOL developed by the EuroQoL Group[22,23]. The questionnaire consists of 2 sections: The EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system contains one question in each of the 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). In the 3-point Likert version (EQ-5D-3L), each question has three levels of response: No problems, some problems or extreme problems. A specific value (weight) is attached to each response of each question according to that country’s specific value sets. Studies have been conducted to elicit preferences from general population samples to derive these value sets. A summary score is calculated by deducting all values of the 5 responses from the full mark of 1. A summary score of 1 represents perfect health, 0 represents death, below 0 represents a state being worse than dead. This summary score could be used for quality adjusted life-year (QALY) calculations. Thus EQ-5D is an important tool for economic valuation. The EQ VAS lets the respondent place an “x” on a vertical VAS to reflect his/her self rated health. The endpoints are labeled "best imaginable health state" at 100 and "worst imaginable health state" at 0
Liver-cancer specific instruments
European Organization for Research and Treatment of Cancer QLQ-HCC18	EORTC QLQ-HCC18 includes eighteen multiple item scales organized into six domains (fatigue, body image, jaundice, nutrition, pain and fever) and two items (abdominal swelling and sex life)[24]. All scales are grouped and transformed to score ranging from 0 to 100. A lower score represents a less severe symptom/problem. EORTC QLQ-HCC18 is used together with EORTC QLQ-C30
Functional Assessment of Cancer Therapy-Hepatobiliary	The FACT-Hep questionnaire is a 45-item instrument for measuring HRQOL in patients with hepatobiliary cancers (liver, bile duct and pancreas)[25]. FACT-Hep is used together with FACT-G. It consists of the 27 items (PWB, FWB, SFWB and EWB domains) in FACT-G together with an 18-item disease-specific hepatobiliary cancer subscale (HepCS) which address specific symptoms of hepatobiliary carcinoma, such as back/stomach pain, gastrointestinal symptoms, anorexia, weight loss, jaundice, as well as side-effects of treatment. An aggregate HepCS score could be obtained. The FACT-G and HepCS scores are summed to form the FACT-Hep total score. Higher scores on all scales of the FACT-Hep reflect better HRQOL or fewer symptoms
Functional Assessment of Cancer Therapy-Hepatobiliary Symptom Index	FHSI-8 is a subset of FACT-Hep. It includes eight items from the FACT-Hep that measure specific symptoms of patient priority concern and side effects of hepatobiliary carcinoma[26]. Higher scores on all items of the FHSI-8 reflect fewer symptoms
Trial Outcome Index	TOI is also a subset of FACT-Hep. It consists of the summation of the PWB, FWB and HepCS subscales[25]. Higher scores reflect better HRQOL and fewer symptoms

EORTC QLQ-C30: European Organization for Research and Treatment of Cancer QLQ-C30; FACT-G: Functional Assessment of Cancer Therapy - General; QoL: Quality of Life; SF-36: Short form 36; SF-12: Short form 12; WHOQOL-100: World Health Organization Quality of Life Assessment 100; FACT-Hep: Functional Assessment of Cancer Therapy-Hepatobiliary; FHSI-8: Functional Assessment of Cancer Therapy - Hepatobiliary Symptom Index; TOI: Trial Outcome Index; HCC: Hepatocellular carcinoma; HRQOL: Health related quality of life.

Table 2 Clinical studies in hepatocellular carcinoma that involved health related quality of life assessment

Ref.	Year	Study type	n	HCC status	Intervention(s)	HRQOL instruments used	HRQOL assessment time point(s)	Remarks
Poon et al[34]	2001	Cohort	76	Resectable and unresectable	Resection (66) vs TACE (10)	FACT-G	Baseline, 3, 6, 7, 12, 18 and 24 mo	Observational study with QOL assessment during treatment
Brans et al[40]	2002	Cohort	26	Unresectable	SIRT (14) vs TACE (14)	EORTC QLQ-C30	Baseline, 1 and 3 mo	Observational study with QOL assessment during treatment
Bianchi et al[32]	2002	Case-control	101	Any stage	NA	SF-36	Baseline	To describe symptomatology and/or HRQOL of HCC patients -HRQOL of HCC patients compared to 202 matched cirrhotic patients
Chow et al[59]	2002	Phase III trial	329	Unresectable	Tamoxifen 120 mg/d (121) vs tamoxifen 60 mg/d (76) vs placebo (132)	Global QOL domain of EORTC QLQ-C30	Baseline, then every 1 mo	Phase III trial with HRQOL endpoint
Steel et al[46]	2004	Cohort	28	Allocated to SIRT or TACE	SIRT (14) vs TACE (14)	FACT-Hep, HepCS, TOI, FHSI8	Baseline, 3, 6 and 12 mo	Observational study with QOL assessment during treatment. Included in[97]
Poon et al[47]	2004	Randomized phase II trial	88	Allocated to TACE	Branched chained amino acid vs control	FACT-G	Baseline, 3, 6, 9 and 12 mo	Phase II trial with HRQOL endpoint
Steel et al[84]	2005	Cohort	82	Any stage	Various treatments	FACT-Hep, HepCS, TOI, FHSI8	Baseline, 3 and 6 mo	To describe symptomatology and/or HRQOL of HCC patients -Compared HRQOL between patients and proxy-raters. Included in[97]
Steel et al[96]	2005	Case-control	21	TNM stage III or IV	NA	FACT-Hep, Sexual History Questionnaire	Baseline	To describe symptomatology and/or HRQOL of HCC patients - Included 23 patients with chronic liver disease
Barbare et al[58]	2005	Phase III trial	420	Not eligible for resection or local treatment	Tamoxifen (210) vs control (210)	Spitzer QoL index	Baseline, then every 3 mo	Phase III trial with HRQOL endpoint
Kirchhoff et al[48]	2005	Randomized phase II trial	70	Eligible for TACE	TACE with microspheres (35) vs TACE (35)	Global QOL of EORTC QLQ-C30	Baseline, then every 6 mo	Phase II trial with HRQOL endpoint
Steel et al[97]	2006	Combined analysis of 3 studies	157	Mixed patient populations from 3 studies	Various treatments	FACT-Hep, HepCS, TOI, FHSI8	Baseline, 3 and 6 mo	Observational study with QOL assessment during treatment - evaluates minimally important difference in HRQOL
Eid et al[36]	2006	Cohort	7	Allocated to hepatic ablation or resection	Hepatic ablation (3) vs resection (4)	EORTC QLQ-C30, FACT-Hep, FHSI8, Profile of Mood States (POMS)	Baseline, postoperative visit, 1.5, 3 and 6 mo	Observational study with QOL assessment during treatment. Study included other liver tumor types (33 patients)
Yeo et al[65]	2006	Combined analysis of 2 phase III trials	233	Unresectable or metastatic	Chemotherapy, hormonal therapy	EORTC QLQ-C30	Baseline	As prognostic tools for overall survival - baseline HRQOL was prognostic of overall survival in advanced HCC
Wang et al[98]	2006	Cohort	83	Non-metastatic, 3 nodules or less	TACE + RFA (43) vs TACE (40)	FACT-G	Baseline, 3 mo	Observational study with QOL assessment during treatment
Cebon et al[49]	2006	Phase I/II trial	63	Not eligible for standard therapies	Octreotide long acting release	FACT-Hep, patient disease and treatment assessment form (Pt DATA form), patient benefit form	Baseline, then every 1 mo	Phase I/II trial with HRQOL endpoint
Llovet et al[12]	2006	Phase III trial	602	Not eligible for local treatment or had disease progression after surgery or local treatment	Sorafenib (299) vs placebo (303)	FHSI-8	Baseline then every 3 wk	Phase III trial with HRQOL endpoint
Lee et al[31]	2007	Case control	161	Any stage	Surgical, TACE, percutaneous ethanol injection, supportive care	EORTC QLQ-C30, WHOQOL-BREF	Cross sectional one-time assessment	To describe symptomatology and/or HRQOL of HCC patients - compared with national matched healthy controls
Kondo et al[37]	2007	Case-control	97	Non-metastatic, 3 nodules or less	Percutaneous ablation	SF-36	Baseline	To describe symptomatology and/or HRQOL of HCC patients - HRQOL compared to 97 matched chronic liver disease controls, and normal population values
Steel et al[33]	2007	Case-control	83	Any stage	NA	FACT-Hep	Baseline	To describe symptomatology and/or HRQOL of HCC patients - HRQOL compared to 51 matched chronic liver disease controls, and 138 controls from general population
Martin et al[35]	2007	Cohort	4	Resectable	Resection	EORTC QLQ-C30, FACT-Hep, FHSI-8	Baseline, discharge, postoperative visit, 1.5, 3, 6 and 12 mo	Observational study with QOL assessment during treatment. Included 28 patients with other liver tumors
Becker et al[50]	2007	Randomized phase II trial	120	Not eligible for resection or local treatment	Octreotide (61) vs placebo (59)	EORTC QLQ-C30	Baseline, 1, 3 mo, then every 3 mo	Phase II trial with HRQOL endpoint
Dimitroulopoulos et al[51]	2007	Randomized phase II trial	127	Advanced stage. Somatostatin receptor overexpression for randomisation	Octreotide (31) vs placebo (30) observation (66)	EORTC QLQ-C30	Baseline then every 1 mo	Phase II trial with HRQOL endpoint
Sun et al[99]	2008	Cohort	22	Mainly advanced disease	Various treatments	FACT-Hep, Functional assessment of chronic illness therapy spirituality subscale (FACIT-Sp-12 )	Baseline, 1, 2 and 3 mo	Observational study with QOL assessment during treatment. Included 23 patients with pancreatic cancer
Méndez Romero et al[52]	2008	Phase I/II trial	9	Not eligible for other local treatments	SBRT	EORTC QLQ-C30 EQ-5D VAS	Baseline, 1, 3 and 6 mo	Observational study with QOL assessment during treatment. Included 19 patients with liver metastases. Phase I/II trial with HRQOL endpoint
Bonnetain et al[66]	2008	Combined analysis of 2 phase III trials[59,101]	538	Not eligible for resection, transplantation or percutaneous ablation	Tamoxifen vs supportive care; TACE + tamoxifen vs tamoxifen	Spitzer QoL index	Baseline	As prognostic tools for overall survival - baseline HRQOL was prognostic of overall survival in advanced HCC
Doffoël et al[100]	2008	Phase III trial	138	Eligible for TACE	TACE + tamoxifen (70) vs tamoxifen (68)	Spitzer QoL index	Baseline, then every 2 mo during treatment, every 3 mo after treatment	Phase III trial with HRQOL endpoint
Barbare et al[60]	2009	Phase III trial	272	Not eligible for curative treatment	Octreotide (135) vs placebo (137)	EORTC QLQ-C30	Baseline, then every 1 mo during treatment, every 3 mo after treatment	Phase III trial with HRQOL endpoint
Cheng et al[13]	2009	Phase III trial	271	Unresectable or metastatic, no prior systemic therapy	Sorafenib (150) vs placebo (76)	FHSI-8. Physical well being domain of FACT-Hep	Baseline then every 3 wk	Phase III trial with HRQOL endpoint
Wible et al[44]	2010	Cohort	73	Allocated to TACE	TACE	SF-36	Baseline, 4, 8 and 12 mo	Observational study with QOL assessment during treatment
Dollinger et al[101]	2010	Phase III trial	135	Locally advanced or metastatic	Thymostimulin (67) vs placebo (68)	FACT = Hep	Baseline then every 3 mo	Phase III trial with HRQOL endpoint
Chow et al[61]	2011	Phase III trial	204	Advanced disease, not eligible for standard therapies	Megestrol acetate (195) vs placebo (69)	EORTC QLQ-C30	Baseline, then every 1 mo during treatment, then every 3 mo after treatment completed	Phase III trial with HRQOL endpoint
Shun et al[102]	2012	Cohort	89	Allocated to TACE	TACE	SF-12, Symptom Distress Scale, Hospital Anxiety and Depression Scale	3 d before discharge, 1 and 2 mo	Observational study with QOL assessment during treatment
Qiao et al[103]	2012	Observational	140	Any stage	NANANAdadsdfsaNA	FACT-epHHep	Baseline	To describe symptomatology and/or HRQOL of HCC patients - HRQOL worsens with advancing stage
Eltawil et al[45]	2012	Cohort	48	Allocated to TACE	TACE	WHOQOL-BREF	Baseline then every 3-4 mo	Observational study with QOL assessment during treatment
Fan et al[104]	2012	Cross sectional	286	Any stage		EORTC QLQ-C30, EORTC QLQ-HCC18	Baseline	To describe symptomatology and/or HRQOL of HCC patients - HRQOL compared with population norms. Correlation between HRQOL and coping and illness perception
Diouf et al[67]	2013	Reanalysis of a phase III trial[61]	215	Not eligible for curative treatment, baseline HRQOL data available	Octreotide vs placebo	EORTC QLQ-C30	Baseline	As prognostic tools for overall survival - baseline HRQOL was prognostic of overall survival in advanced HCC. HRQOL data may improve existing staging systems
Soliman et al[53]	2013	Phase II trial	21	Not eligible for or refractory to standard therapies, symptomatic	Liver radiotherapy	EORTC QLQ-C30, FACT-Hep, HepCS, TOI, FACT-G	Baseline, 1, 3 and 6 mo	Phase II trial with HRQOL endpoint. Included 20 patients with liver metastasis
Salem et al[41]	2013	Cohort	56	Allocated to SIRT or TACE	SIRT (29), TACE (27)	FACT-Hep	Baseline, 2 and 4 wk	Observational study with QOL assessment during treatment
Brunocilla et al[105]	2013	Cohort	36	Allocated to sorafenib	Sorafenib	FACT-Hep, FHSI-8, FACT-G	Baseline, 1 wk, 1 and 2 mo	Observational study with QOL assessment during treatment
Johnson et al[62]	2013	Phase III trial	1150	Not eligible for resection or local treatment, no prior systemic treatment	Brivanib (577) vs sorafenib (578)	Physical function and role function of EORTC QLQ-C30	Baseline then every 6 wk	Phase III trial with HRQOL endpoint
Meyer et al[63]	2013	Phase II/III trial	86	Unresectable, non-metastatic	TACE vs TAE	EORTC QLQ-C30, EORTC QLQ-HCC18	Baseline, 1.5, 3 and 6 mo	Phase II trial with HRQOL endpoint
Mise et al[106]	2014	Cohort	69	Allocated to resection	Resection	SF-36	Baseline then every 3 mo	Observational study with QOL assessment during treatment
Huang et al[38]	2014	Cohort	388	Solitary HCC ≤ 3 cm	Resection, radiofrequency ablation	FACT-Hep, HepCS, TOI, FACT-G	Baseline, 3, 6, 12, 24 and 36 mo	Observational study with QOL assessment during treatment
Zhu et al[64]	2014	Phase III trial	564	Progressive disease during or after sorafenib	Everolimus (362) vs placebo (184)	Global QOL and physical function of EORTC QLQ-C30	Baseline, then multiple reassessments	Phase III trial with HRQOL endpoint
Palmieri et al[107]	2015	Case control	24	Any stage	NA	SF-36	Baseline	To describe symptomatology and/or HRQOL of HCC patients - evaluates relationship between psychological profile and HRQOL in HCC. Included 22 cirrhotic patients without HCC, 20 control subjects
Chie et al[108]	2015	Cohort	171	Allocated to respective treatments	Surgery (53), ablation (53), TACE (65)	EORTC QLQ-C30, EORTC QLQ-HCC18	Baseline, then 4-6 wk for post-ablation/post-TACE, 12-15 wk post-operation	Observational study with QOL assessment during treatment
Heits et al[109]	2015	Cross sectional	173	Allocated to liver transplanation	liver transplantation	EORTC QLQ-C30	At one variable time point post-transplantion	To describe symptomatology and/or HRQOL of HCC patients
Xie et al[110]	2015	Cohort	102	Allocated to resection or TACE	resection (58), TACE (44)	SF-36	Baseline, 1, 3, 6, 12 and 24 mo	Observational study with QOL assessment during treatment
Xing et al[111]	2015	Cohort	118	Allocated to TACE	TACE with doxorubicin eluted beads	SF-36	Baseline, 1-3, 6 and 12 mo	Observational study with QOL assessment during treatment
Kolligs et al[54]	2015	Randomized phase II trial	28	Allocated to SIRT or TACE	SIRT (13), TACE (15)	FACT-Hep	Baseline, then every 6 wk	Phase II trial with HRQOL endpoint
Klein et al[42]	2015	Combined analysis of prior phase I/II trials	98	Allocated to SBRT	SBRT	EORTC QL-C30, FACT-Hep	Baseline, 1, 3, 6 and 12 mo	Phase I/II trial with HRQOL endpoint
Kensinger et al[48]	2016	Case-control	139	Allocated to priority liver transplantation	Liver transplantation	SF-36	Baseline, post transplantation	Observational study with QOL assessment during treatment - included 362 subjects without HCC
Lei et al[39]	2016	Cohort	205	Allocated to resection or transplantation	Liver transplantation (110), resection (95)	SF-36	Baseline, then every 1-2 mo for the first 6 mo, then every 2-3 mo for the next 6 mo, then every 6 mo	Observational study with QOL assessment during treatment
Yang et al[112]	2016	Cohort	17	Portal vein thrombosis	TACE and transarterial ethanol ablation	EORTC QLQ-C30	Baseline then every 1 mo	Observational study with QOL assessment during treatment
Anota et al[55]	2016	Phase I trial	21	Not eligible for curative treatment	TACE with idaurubicin eluted beads	EORTC QLQ-C30	Baseline, 15, 30 and 60 d	Phase I trial with HRQOL endpoint
Chie et al[88]	2016	Case-control	227	Any stage	Various treatments	EORTC QLQ-C30, EORTC QLQ-HCC18	Baseline, post-treatment	Observational study with QOL assessment during treatment - Compared HRQOL between Asian and European HCC patients
Lv et al[56]	2016	Randomized phase II trial	120	Allocated to TACE	COX2 inhibitor (60) vs placebo (60)	Locally developed questionnaire	Baseline, 24 and 48 h	Phase II trial with HRQOL endpoint
Koeberle et al[57]	2016	Randomized phase II trial	106	Unresectable or metastatic	Sorafenib + everolimus (60) vs sorafenib (46)	FACT-HepCS, EQ-VAS	Baseline, then every 2 wk until week 12	Phase II trial with HRQOL endpoint
Shomura et al[113]	2016	Cohort	54	TNM stage IV	Sorafenib	SF-36	Baseline, then every 3 mo	Observational study with QOL assessment during treatment
Bruix et al[14]	2016	Phase III trial	573	Progressive disease during sorafenib	Regorafenib (379) vs placebo (193)	FACT-Hep, TOI, FACT-G, EQ-5D, EQ-VAS	Baseline, then multiple reassessments	Phase III trial with HRQOL endpoint
Li et al[69]	2017	Cohort	472	Any stage	Various treatments	EORTC QLQ-C30, EORTC QLQ-HCC18, C30 index score, HCC18 index score	Baseline	As prognostic tools for overall survival - baseline HRQOL was prognostic of overall survival in advanced HCC. QOL derived scoring system resembles a staging system

EORTC: European Organisation for Research and Treatment of Cancer; EQ-5D: EuroQoL-5D; FACT-G: Functional Assessment of Cancer Therapy - General; FACT-Hep: Functional Assessment of Cancer Therapy - Hepatobiliary; FHSI-8: Functional Assessment of Cancer Therapy - Hepatobiliary Symptom Index; HCC: Hepatocellular carcinoma; HepCS: Hepatobiliary cancer subscale; HRQOL: Health related quality of life; n: Sample size; NA: Not applicable; RFA: Radiofrequency ablation; SBRT: Stereotactic body radiation therapy; SF-12: Short Form 12; SF-36: Short Form 36; SIRT: Selective internal radiation therapy; Spitzer QoL Index: Spitzer Quality of Life Index; TACE: Transarterial chemoembolization; TOI: Trial Outcome Index; VAS: Visual analogue scale; WHOQOL-BREF: World Health Organization Quality of Life Assessment abbreviated version.

Table 3 Algorithm of C30 and HCC18 index scores

QOL Index scores for survival prognostication
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/vomiting, Pain, Dyspnoea, Insomnia, Appetite loss, Constipation, Diarrhea, Financial Difficulty]/15
HCC18 index score	∑(scores of Fatigue, Body Image, Jaundice, Nutrition, Pain, Fever, Sex life, Abdominal distension)/8

QOL: Quality of life.