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.