**2. Methods for studying QOL**

In practice most research has measured HRQOL as a multi-dimensional construct, instruments used to measure it must have at least three core domains: physical, psychological and social (Unal, 2001; Drent, 2009). Broadly speaking QOL measures can be divided into two categories: generic or condition-specific (Patrick, 1989; van den Plas, 2003):

#### **2.1 Generic questionnaires**

Generic questionnaires are comprehensive and they can apply to different patient populations, allowing comparisons between different diseases. These generic measures have the advantage that the obtained scores can be compared with the scores of other patient populations or with a healthy control group, stratified by age and gender. A recognized disadvantage is that generic instruments are not designed to identify disease specific domains which may be important when we want to establish whether clinical changes have occurred and whether or not they are significant (Jay, 2009).

In the last few years one of the major clinical concerns has been to obtain a good level of QOL after therapeutic interventions. It is therefore crucial to study QOL by asking questions which are relevant to the patients (Hays, 2000). The concept of patient reported outcome is related to an in depth study of the meaningful changes perceived by the patients (Gill, 1994).

A patient-reported outcome (PRO) can be defined as "any outcome based on data provided by patients or by patient proxy as opposed to data provided from other sources". PROs that are of importance to liver transplant patients are: symptom experience, medication adherence and HRQOL. The effectiveness of treatment after organ transplantation depends both on the skills of the health care team and on the life-long, active cooperation of the patient. (Bayliss,1999).

The clinical information provided to the patient and caregivers about long-term side effects of drugs, and of the possibility of developing recurrent or "de novo" disease is essential (Nickel, 2002). This means that transplantation will have an impact on the daily life and the well-being of the patient and will remain as a chronic condition (Stewart, 1989). The three most commonly used generic HRQOL instruments are: the Nottingham Health Profile (NHP), the Medical Outcomes Study Short Form-36 (SF-36) and the Sickness Impact Profile (SIP). (Table 2) (Coons, 2000; Hunt, 1980; de Bruin, 1992; Bergner, 1976). All three instruments have sufficient psychometric properties.

*The Medical Outcomes Study 36-item Short Form Health Survey (SF-36),* consists of 36 items which measure eight scales: physical functioning (PF), (10 items), role limitations due to physical problems (RP), (4 items), bodily pain (BP), (2 items), general health (GH), (5 items), vitality (VT), (4 items), social functioning (SF), (2 items), role limitations due to emotional problems (RE), (3 items), and mental health (MH) (5 items). On the basis of these separate subscales, component summary scores can be calculated to provide a global measure of physical (Physical Component Summary score, PCS) and mental functioning (Mental Component Summary score, MCS), respectively. The scale scores range from 0 to 100, with higher scores indicating a better health status. The PCS and MCS have been standardized on the basis of a normative general population of different countries, with the mean set at 50 (SD 10) (Guyatt,1993) The SF-36 is currently the most used instrument worldwide, and a shorter version is available (SF-12) (Bruns, 2010).
