key: cord-0794501-xwabahjz
authors: Gitto, Stefano; Golfieri, Lucia; Mannelli, Nicolò; Tamè, Maria Rosa; Lopez, Ivo; Ceccato, Roberta; Montanari, Stanislao; Falcini, Margherita; Vitale, Giovanni; De Maria, Nicola; Presti, Danilo Lo; Marzi, Luca; Mega, Andrea; Valente, Giovanna; Borghi, Alberto; Foschi, Francesco Giuseppe; Grandi, Silvana; Forte, Paolo; Cescon, Matteo; Di Benedetto, Fabrizio; Andreone, Pietro; Arcangeli, Giulio; De Simone, Paolo; Bonacchi, Andrea; Sofi, Francesco; Morelli, Maria Cristina; Petranelli, Marco; Lau, Chloe; Marra, Fabio; Chiesi, Francesca; Vizzutti, Francesco; Vero, Vittoria; Di Donato, Roberto; Berardi, Sonia; Pianta, Paolo; D’Anzi, Sharon; Schepis, Filippo; Gualandi, Noemi; Miceli, Francesca; Villa, Erica; Piai, Guido; Valente, Marco; Campani, Claudia; Lynch, Erica; Magistri, Paolo; Cursaro, Carmela; Chiarelli, Annarita; Carrai, Paola; Petruccelli, Stefania; Dinu, Monica; Pagliai, Giuditta
title: Quality of life in liver transplant recipients during the Corona virus disease 19 pandemic: A multicentre study
date: 2022-04-02
journal: Liver Int
DOI: 10.1111/liv.15260
sha: 218987550cde10f0c902234243191fa14dbebbca
doc_id: 794501
cord_uid: xwabahjz

BACKGROUND: Liver transplant recipients require specific clinical and psychosocial attention given their frailty. Main aim of the study was to assess the quality of life after liver transplant during the current pandemic. METHODS: This multicentre study was conducted in clinically stable, liver transplanted patients. Enrollment opened in June and finished in September 2021. Patients completed a survey including lifestyle data, quality of life (Short Form health survey), sport, employment, diet. To examine the correlations, we calculated Pearson coefficients while to compare subgroups, independent samples t‐tests and ANOVAs. To detect the predictors of impaired quality of life, we used multivariable logistic regression analysis. RESULTS: We analysed data from 511 patients observing significant associations between quality of life’s physical score and both age and adherence to Mediterranean diet (p < .01). A significant negative correlation was observed between mental score and the sedentary activity (p < .05). Female patients scored significantly lower than males in physical and mental score. At multivariate analysis, females were 1.65 times more likely to report impaired physical score than males. Occupation and physical activity presented significant positive relation with quality of life. Adherence to Mediterranean diet was another relevant predictor. Regarding mental score, female patients were 1.78 times more likely to show impaired mental score in comparison with males. Sedentary activity and adherence to Mediterranean diet were further noteworthy predictors. CONCLUSIONS: Females and subjects with sedentary lifestyle or work inactive seem to show the worst quality of life and both physical activity and Mediterranean diet might be helpful to improve it.

health, economic and employment crisis has led a vast part of the population to express worry for the next 5 years. 4 Today, many subpopulations could require specific clinical and psychosocial attention, given their risk factors in terms of mental and physical health. Among them, patients who underwent liver transplantation (LT) are especially vulnerable, and previous research indicated higher depression and need for social support than general population. 5 Transplant recipients often experience negative psychological outcomes, such as re-experiencing, avoidance, a sense of anticipation and responsibility towards the donor, clinicians and family members. [6] [7] [8] LT represents the standard of care for patients with severe acute or chronic liver diseases or hepatocellular carcinoma, with 1-and 5-year patient survival rates of more than 90% and 70% respectively. 9, 10 With these remarkable survival rates, quality of life (QoL) should represent today a chief independent measure of transplant outcome. 11, 12 Notably, the goal of LT should be not only to achieve an acceptable QoL, but to return to the levels present before the onset of liver disease. 13, 14 Considering the relevance of QoL in the overall assessment of the success of LT, this study was undertaken to examine the QoL of a large population of LT recipients during the COVID-19 pandemic.

Specifically, we aimed (a) to analyse the correlation between personal data, lifestyle patterns, physical activity, employment and adherence to Mediterranean diet and QoL of LT recipients during the COVID-19 pandemic; and (b) to detect the predictors of impaired QoL.

This cross-sectional, multicentre study was conducted in clinically stable, adult patients who underwent LT and were followedup 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. 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. In each of the nine European countries, there were wide correlations between the measures from the SF-36 and SF- 12. 22 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 countryspecific 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. 22 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 (IPAQ) measures multiple domains of physical activity. 23

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. 24 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 vigorousintensity 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 vigorousintensity 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. 23 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). 23 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 24 ; therefore, we used the short version. 

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. 26 For each food group, there are three categories of consumption. 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%. 27 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.

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.

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, 32 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 ttest (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 (ηp 2 ) 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.

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 33 (lower values and non-significance indicate a good fit to the data) and Nagelkerke R 234 (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.

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. 35 The other recommended rules of thumb include the following: n = 100 + 50i, where i refers to number of independent variables in the final. 35 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, 36 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. 37 

The questionnaire was administered to 511 patients (71% men) with a mean age of 63.1 yrs (SD ± 10.8). Data on socio-demographic and clinical information on tobacco and alcohol use are reported in Table 1 .

Means, standard deviations and bivariate correlations of the SF-12 physical (PCS-12) and mental (MCS-12) with age, sedentary activity score of the IPAQ (SA-IPAQ) and the MEDI-LITE score are shown in Table 2 . We observed statistically relevant correlations of the PCS-12 score with age and the MEDI-LITE score (p < .01). Moreover, a significant negative correlation was observed between MCS-12 and the IPAQ sedentary activity score (p < .05). All the other correlations were not significant. 506] = 6.32, p < 0.01, ηp 2 = .024). Post hoc tests revealed that patients from Central Italy showed higher physical health than patients from other areas (p < 0.01), inactive/retired patients experienced lower physical health than blue (p < 0.01) and white (p < 0.01) collars.

Patients with low physical activity reported lower physical health than those with medium (p < 0.001) or high (p < 0.001) activity, and patients who occasionally consume alcohol showed better physical health than patients who never (p < 0.05) or continuously (p < 0.01) drink alcohol. Mean PCS-12 and MCS-12 scores in relation to these parameters are displayed in Figure 2. 

Preliminarily, PCS-12 and MCS-12 outcome variables were dichotomized using the 25th percentile (corresponding to 41 and 42 respectively). Since inactive/retired patients reported lower PCS-12 scores when compared to blue and white collars, but no differences were detected between these two groups, the predictor variable "occupation" was transformed in a dichotomous variable (i.e., inactive/retired vs. blue/white collars). Similarly, because medium and high activity patients did not differ on PCS-12, the predictor "physical activity" was also dichotomised (i.e., low physical activity vs. medium/high activity). Finally, place of stay was not included as predictor because the variable is specifically related to the geographical characteristics of Italy and the geographical location of the Hepatology Units.

In Table 3 , we reported frequencies and percentages for each predictor and the relative statistics tests to compare the two groups defined upon the 25th percentile of the PMC-12 and MCS-12 scores (i.e., impaired vs. not impaired QoL groups). Except for the difference in the MEDI-LITE score that was observed also between groups based on the 25th percentile of the MCS-12, results are in line with the previous reported analyses, and they can be resumed as follows.

Comparing the impaired versus not impaired physical health groups, higher percentages of female, unemployed/retired, low activity, low adherence to the diet, older patients belonged to the impaired group. Comparing the impaired versus not impaired mental health groups, higher percentages of female, sedentary activity and low adherence to the diet patients belonged to the impaired group.

The specific weight of each predictor is reported in Table 4 .

Female patients were 1.65 times more likely to report impaired PCS-12 than males. Occupation and physical activity also displayed a significant positive in relation to QoL, indicating that workers or patients with medium/high activity were less likely to report impaired PCS-12 than unemployed/retired or low activity patients (Odds ratio 1.77 and 3.71 respectively). MEDI-LITE score was also a relevant predictor, and for each one-point increase in the score, the patient was .84 times less likely to report impaired QoL.

When mental health was analysed (Table 4) , female patients were 1.78 times more likely to report impaired MCS-12 than male patients. Sedentary activity and the MEDI-LITE score were additional significant predictors, and for each one-point increase in the score, the patient was 1.51 more likely and .88 times less likely to report impaired MCS-12 respectively. We found that female patients had significantly lower scores than males in both PCS-12 and MCS-12. Of note, females experience numerous challenges in the post-transplant period, which may include greater risk for osteoporosis upon post-menopause metabolic changes. 38 Desai et al. 39 demonstrated that after LT, female gender was associated with a worse QoL (in PCS-12) than males. Notably, women show lower levels of QoL than men also in other contexts such as older adults 40 or patients with cardiovascular disease. 41 Thus, our data and those of previous studies indicate that clinical practitioners should pay special attention to LT female recipients seeking treatment and offer specialized medical and psychosocial resources to address their unique needs.

Our data about the positive impact of physical activity on QoL are coherent with data reported in other studies. Post-transplant physical activity, self-care, mobility and total energy expenditure were all associated with improved QoL in LT recipients. 42 Interestingly, involvement in group sport activities was associated with improved physical function and QoL. 43, 44 According to our data, a sedentary lifestyle independently correlated with both MCS-12 and PCS-12 and patients reporting low physical activity had lower PCS-12 than subjects with medium and high activity. Along these lines, we also provide evidence that inactive or retired patients experienced lower PCS-12 than active workers, independently of the type of occupation (blue-or white-collar). Both physical activity and occupation maintained a significant positive correlation to QoL in the multivariate model, indicating that patients on a medium/high activity or an active working status are less likely to report impaired PCS-12 than unemployed/retired or low activity patients.

An original finding of the present study is that adherence to a Mediterranean diet is a significant and independent predictor of better QoL in LT. These data are in line with those recently reported 45 in a large cohort study in the Italian general population, demonstrating that adherence to a Mediterranean diet was related to an enhanced perceived QoL. A positive association between Mediterranean diet and QoL was also reported by Galilea-Zabalza et al. 46 In conclusion, considering LT recipients, females and patients with sedentary lifestyle or work inactive seem to show lower QoL scores than their counterpart. Sport activities and a Mediterranean diet might help LT recipients to improve their QoL.

The transplant community might implement a network of information and support encouraging physical activity and adherence to a healthy Mediterranean-style diet. Further targeted studies should better investigate the gender differences by attempting to eliminate the clinical and social disadvantages of women.

Nothing to declare.

The present study was approved by the Local Independent Ethics

Committee ("Comitato Etico Area Vasta Centro") (approval number 20659).

Patients provided informed consent before participating in the study.

A special thanks to "Vite-Volontariato Italiano Trapiantati Epatici"

for their continuous effort in support of transplanted patients of our communities, and for collaborating to the present study. A special thanks to "Vita che rinasce-Associazione Trapiantati Modena" for their unvaluable support for the present study.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

https://orcid.org/0000-0002-8042-6508

Giovanni Vitale https://orcid.org/0000-0003-2603-8245

Pietro Andreone https://orcid.org/0000-0002-4794-9809

Fabio Marra https://orcid.org/0000-0001-8629-0878

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