Material and Methods
This cross-sectional, multicentre study was conducted in clinically stable, adult patients who underwent LT and were followed-up in seven Italian Hepatology Units. Inclusion criteria were the following: age ≥18 years, LT performed at least 12 months earlier, and absence of clinical events during the last 6 months. Multiorgan transplant or re-transplantation, vascular or biliary complications, systemic disorders (e.g. cardiovascular disease, cancer, infection, recurrence of pre-LT liver disease), unstable conditions, hospital admission in the last 6 months represented the exclusion criteria. Human Immunodeficiency Virus infection, deafness, inability to carry out a telephone interview in full understanding or holiday in the last 4 weeks were additional exclusion criteria.
The enrollment started on 1 June 2021 and ended on 30 September 2021.
Patients provided informed consent before participating in the study. Then, trained professional staff agreed on the date and time of a subsequent interview, during which the patient could answer by telephone to the composite questionnaire. We requested that the patient be alone in a silent space.
The first part of the survey consisted of a demographic questionnaire. In particular, the following personal and lifestyle data were recorded: gender, age, transplant date, referral centre, region of residence, education degree, presence of caregiver, alcohol and tobacco habits. Subsequently, patients completed 4 questionnaires in an estimated total time of 10–15 min.
The Short Form Health Survey. The Short Form health survey (SF-12) is a health-related QoL questionnaire consisting of 12 questions that measure 8 health domains to evaluate physical and mental health. The SF-12 represents a commonly used tool to assess health-related QoL. It is a shorter version of SF-36 developed by Ware et al.. Physical health-related domains include General Health, Physical Functioning, Role Physical and Body Pain. Mental health-related scales comprise Vitality, Social Functioning, Role Emotional and Mental Health. The SF-12 has demonstrated strong reliability and validity across many chronic illnesses and conditions.[17–21] We administered the SF-12, and for each participant, we calculated two summary scores of physical (Physical Component Summary, PCS-12) and mental (Mental Component Summary, MCS-12) health, using the weighted means of the eight domains.
In each of the nine European countries, there were wide correlations between the measures from the SF-36 and SF-12. Correlations were also significant between scores based on three different estimation methods (standard items and scoring weights; standard items and country-specific scoring weights; and country-specific items and scoring weights). Mean scores were also comparable across estimation methods. Furthermore, there was a high degree of replication in the selection of 12 items for the SF-12 across 9 European countries and in comparison with items selected for the North-American SF-12 version.
The SF-12 covers the same eight health domains as the SF-36 with considerably fewer questions, making it a more practical instrument.
The International Physical Activity Questionnaire-short Version. The International Physical Activity Questionnaire (IPAQ) measures multiple domains of physical activity.
The IPAQ-short version includes 11 items regarding time spent on walking, vigorous- and moderate-intensity activity, sedentary activity and demographic information (including education) and some last items concerning comprehension of the questionnaire. Information regarding physical activity was expressed in min per day and/or days per week. Then, there are three levels (low, moderate, high) of physical activity proposed to classify populations. The "high" category includes (a) vigorous-intensity activity on at least 3 days achieving a minimum total physical activity of at least 1500 Metabolic Equivalent Task (MET)-min/week or (b) 7 or more days of any combination of walking, moderate-intensity or vigorous-intensity activities achieving a minimum total physical activity of at least 3000 MET-minutes/week. The pattern of activity can be classified as "moderate" if (a) 3 or more days of vigorous-intensity activity of at least 20 min per day, or (b) 5 or more days of moderate-intensity activity and/or walking of at least 30 min per day or (c) 5 or more days of any combination of walking, moderate-intensity or vigorous-intensity activities achieving a minimum total physical activity of at least 600 MET-minutes/week. Individuals who do not meet criteria for high or medium categories are considered to have a "low" physical activity level. The IPAQ has been developed as an instrument for cross-national evaluation of physical activity and has been validated in 12 countries including Italy.[24,25]
The IPAQ also provides an indicator of sedentary activity that is not included as part of any summary score of physical activity. Indeed, the IPAQ assesses time spent in sitting on a typical week expressed in "minutes" (Sitting Total Minutes/week = weekday sitting minutes × 5 weekdays + weekend day sitting minutes × 2 weekend days).
The IPAQ is present in two versions: long and short. The long version of questionnaire appeared less pleasant and more confusing in comparison with the short one; therefore, we used the short version.
Employment. We also evaluated the post-transplant resumption of work with both closed and open ad hoc questions. Indeed, we designed a specialized employment questionnaire.
The enrolled subjects answered the following questions concerning the work activity: "Today, are you an active worker? Which kind of job (then classified in 'blue' or 'white collar' job) are you doing in the present period or have worked in the past respectively? If inactive, how long have you been in this state? Have you ever received an inability pension or has been in a protected categories (according to the Italian Law number 68/99)?"
If patients were inactive, the questionnaire was finished. If patients were active workers, the following question was proposed: "After LT, were you placed in the same job responsibilities of the pre-transplant period? If not, what task was you assigned after transplant? Who evaluated the return to work after transplant? If the return was valued by the Occupational Health Physician, were the tasks customized? Did you receive some limitations or prescriptions? If yes, which?"
Finally, we asked to provide an overall judgement about the return to work after transplant and about the physical demand required with the use of two Likert scales.
"On a scale of 1 (very easy) to 5 (very difficult), in general terms, as you would define your reintegration into work? On a scale of 1 (very easy) to 5 (very hard), how would you define your return to work from a physical point of view?"
MEDI-LITE Score. To evaluate adherence to Mediterranean diet, we used the MEDI-LITE score, proposed in 2014 and validated in 2017.[26,27] The MEDI-LITE score consists of nine items about daily consumption of fruit, vegetables, cereals, meat and meat products, dairy products, alcohol and olive oil and the weekly intake of legumes and fish. For each food group, there are three categories of consumption. For foods typical of Mediterranean diet (fruit and vegetables, cereals, legumes and fish), 2 points are assigned to the highest consumption category, 1 to the middle category and 0 to the lowest category. As to olive oil, 2 points are assigned for regular use, 1 for frequent use and 0 for occasional use. Foods not representative of the Mediterranean diet (meat and meat products, dairy products) are scored as follows: 2 points to the lowest category, 1 to the middle category and 0 to the highest category of consumption. Finally, 2 points are assigned to the middle consumption category of alcohol (1–2 alcohol units/day), 1 to the lowest category (1 alcohol unit/day) and 0 to the highest category (>2 alcohol units/day). The final score ranges from 0 (low adherence) to 18 (high adherence to the Mediterranean diet).
The MEDI-LITE score revealed a noteworthy discrimination capacity of 85%. The MEDI-LITE score that best discriminated between adherents and non-adherents (optimal cut-off point) was 8.50. The sensitivity for this cut-off value was 96% and the specificity was 38%. For this reason, the tool was used and proposed by many authors in dissimilar subgroups.[28–31]
All analyses were conducted on SPSS (version 27.0). As first step, we examined the missing values. Pairwise deletion was used when a case had missing answers.
Sample Description. Descriptive statistics, such as frequencies, percentages, mean [±standard deviation (SD)] or median (and range and/or quartiles), were used to describe the sample's characteristics.
Preliminary Analyses to Select Quality of Life-related Variables. To investigate the relationships between personal data, lifestyle patterns, physical activity, employment and adherence to Mediterranean diet and QoL, we computed the Pearson Product Moment Correlation coefficients. To compare two or more subgroups, we used the independent samples t-tests (if two) and one-way ANOVAs (if more than two) with Bonferroni post hoc (i.e., multiple comparisons between every possible combination of pairs were carried out). In detail, Pearson's correlations were calculated for PCS-12 and MCS-12 scores, age and MEDI-LITE score. According to Cohen, a correlation coefficient from .10 to .30 represents a weak or small association, a correlation coefficient from .30 to .50 is considered a moderate correlation and a correlation coefficient of .50 or larger is thought to represent a strong or large correlation. Differences in PCS-12 and MCS-12 scores were assessed using t-tests to compare gender, caregiver (yes, no), smoking (yes, no), independent groups and one-way ANOVAs to compare educational level (primary school, secondary school, high school and university), place of stay in Italy (north, centre, south) independent groups, occupation (blue collar, white collar, unemployed/retired), time from LT (1–5 yrs, 6–10 yrs, more than 10 yrs), alcohol consumption (no, occasionally, continuously), and level of physical activity (low, medium, high). As measures of effect size (Cohen, 1992), d was used for t-test (values from 0.2 to 0.5 are indicators of a small effect, values from 0.5 to 0.8 represent a medium effect and values from 0.8 a large effect), the partial eta squared (ηp2) for ANOVAs (values lower than 0.06 suggest a small effect, values from 0.06 to 0.14 a medium effect, values from 0.14 a large effect). Finally, χ 2 tests were used to compare dichotomized PCS-12 and MCS-12 scores and the above-mentioned categorical variables of the study. All together, these analyses were used to identify the potential predictors of impaired QoL.
Multivariate Analysis to Identify Predictors of Impaired Quality of Life. A multivariable logistic regression analysis was performed to identify independent predictors of QoL. We used the 25th percentile/1st quartile as a cutoff to identify impaired QoL (1 = scores lower or equal to 25th percentile) versus not impaired Qol (0 = scores higher than the 25th percentile) as outcome variable, and to include both metric and categorical variables (dichotomous or polytomous) as independent predictors. As indicators of overall model evaluation, we referred to Hosmer–Lemeshow inferential goodness-of-fit test (lower values and non-significance indicate a good fit to the data) and Nagelkerke R2 (values range from 0 to 1). The degree to which predicted probabilities agree with actual data is expressed as a classification table. Statistical significance of individual predictors was tested using the Wald chi-square statistic (p < .05). The resultant predicted probabilities (odds ratios) can be used to determine if higher or lower probabilities are indeed associated with an event (i.e., impaired QoL) given the different levels of the predictor variables (e.g., being male or female). Odds ratios were associated with the 95% confidence interval.
Sample Size. For observational studies that involve logistic regression in the analysis, taking a minimum sample size of 500 is typically necessary to derive the statistics that represent the parameters. The other recommended rules of thumb include the following: n = 100 + 50i, where i refers to number of independent variables in the final. In line with the aims of the current study, we hypothesized that at least 8 predictors (gender, age, smoking and alcohol habits, employment, educational level, physical activity and adherence to Mediterranean diet will be included in the analysis) will account for the outcome variable. As such, we calculated to enrol at least 500 patients (i.e., 100 + [50x8] = 500).
The present study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments, and it was approved by the Local Independent Ethics Committee ("Comitato Etico Area Vasta Centro") (approval number 20659).
The reporting of this study conforms to STROBE guidelines.
Liver International. 2022;42(7):1618-1628. © 2022 Blackwell Publishing