Biopsychosocial profile of non-alcoholic fatty liver disease (NAFLD) associated with liver transplantation and prevention of risk factors

En la presente Tesis Doctoral se han llevado a cabo un estudio teórico y cinco trabajos empíricos y pioneros que abordan principalmente distintos perfiles biopsicosociales de pacientes con EHGNA asociados, por un lado, a los distintos niveles de gravedad de la enfermedad hepática y, por otro lado, a sus principales factores de riesgo, es decir, la diabetes tipo 2 y la obesidad. También se explora la relevancia de los biomarcadores psicológicos en la adherencia terapéutica de los pacientes con EHGNA. En concreto, en el primer trabajo el objetivo era realizar un estudio teórico sobre las principales repercusiones psicosociales de la EHGNA, así como discutir aquellos biomarcadores psicológicos que pueden ser relevantes para el perfil biopsicosocial asociado a la EHGNA. En cuanto al impacto de la EHGNA, ésta parece asociarse a un deterioro de la calidad de vida, principalmente a nivel físico, y de la salud mental, reportando estos pacientes una mayor sintomatología ansiosa y depresiva que en otras patologías hepáticas crónicas. Además, las estrategias de afrontamiento, la autoeficacia o el apoyo social son definidas como variables potencialmente relevantes para la EHGNA por sus posibles efectos sobre la salud física y mental, y la adherencia terapéutica de estos pacientes. Finalmente, se sugiere la inclusión de técnicas cognitivo-conductuales dentro de una intervención multidisciplinar de la EHGNA. En el segundo trabajo el objetivo era comparar la calidad de vida, salud mental y estrategias de afrontamiento de pacientes con EHGNA en función del apoyo social y de la esteatohepatitis y fibrosis hepática, así como determinar qué marcadores histológicos y psicosociales predicen la calidad de vida de estos pacientes. Para ello, se aplicaron una serie de cuestionarios a una muestra de 492 pacientes con EHGNA diagnosticada mediante biopsia hepática: Cuestionario de Salud SF-12, Cuestionario para pacientes con Enfermedad Hepática Crónica CLDQ-NAFLD, Escala Hospitalaria de Ansiedad y Depresión, Inventario de Depresión de Beck, Cuestionario de Afrontamiento COPE-28, Escala de Autoeficacia General, y Escala Multidimensional de Apoyo Social Percibido. Luego se llevaron a cabo diferentes pruebas estadísticas de análisis de la varianza, comparación de medias y regresión logística binaria, que permitieron llegar a la conclusión de que un bajo apoyo social y un nivel significativo de fibrosis se asocian con una peor calidad de vida y salud mental, y con un estilo de afrontamiento más desadaptativo, en comparación con aquellos pacientes con un alto apoyo social y sin fibrosis significativa. Los pacientes con fibrosis significativa también mostraron un mayor deterioro en su calidad de vida en comparación con la población general española. Asimismo, la fibrosis significativa, junto con el género femenino y una mayor sintomatología ansiosa y depresiva, fueron establecidos como predictores significativos del deterioro en la calidad de vida de los pacientes con EHGNA. El objetivo en el tercer trabajo de esta Tesis era comparar la calidad de vida de pacientes con EHGNA en función de su lugar de procedencia, la esteatohepatitis y la fibrosis, así como establecer qué marcadores histológicos y biopsicosociales predicen la calidad de vida en los pacientes de España y de Reino Unido. También se pretendió determinar qué marcadores biopsicosociales ejercen un rol mediador o moderador en modelos predictores de la calidad de vida en los pacientes con EHGNA. Para ello, el Cuestionario para pacientes con Enfermedad Hepática Crónica CLDQ fue aplicado a una muestra de 737 pacientes con EHGNA diagnosticada mediante biopsia hepática (447 pacientes de España y 290 del Reino Unido). Luego fueron llevadas a cabo diferentes pruebas estadísticas de análisis de la varianza, regresión logística binaria y modelos de mediación y mediación moderada, que permitieron llegar a la conclusión de que los pacientes del Reino Unido tienen una peor calidad de vida física y mental que los de España. Además, un mayor nivel de fibrosis predijo una peor calidad de vida, fundamentalmente en la cohorte española. Tanto el género femenino como un mayor índice de masa corporal contribuyeron al impacto negativo sobre la calidad de vida tanto en España como en el Reino Unido. Finalmente, el género femenino predice una peor calidad de vida al asociarse con una peor función emocional, un mayor índice corporal y una mayor fatiga, siendo este impacto negativo sobre la calidad de vida superior en pacientes del Reino Unido. El cuarto trabajo de esta Tesis tuvo como objetivo determinar los biomarcadores psicológicos, hepáticos y metabólicos que ejercen un rol mediador o moderador en modelos predictores de la salud mental y autoeficacia de pacientes con EHGNA. Para ello, se aplicaron los siguientes cuestionarios a una muestra de 509 pacientes con EHGNA diagnosticada mediante biopsia hepática: Cuestionario de Salud SF-12, Inventario de Depresión de Beck, Cuestionario de Afrontamiento COPE-28 y Escala de Autoeficacia General. Luego se llevaron a cabo análisis estadísticos basados en modelos de mediación moderada, que permitieron llegar a la conclusión de que un estilo de afrontamiento desadaptativo se vincula con una peor calidad de vida física y mental en pacientes con EHGNA lo que, sumado a la presencia de diabetes, un mayor índice de masa corporal y un nivel significativo de fibrosis, predicen una peor salud mental o autoeficacia en estos pacientes. El objetivo principal en el quinto trabajo de la presente Tesis Doctoral fue comparar la calidad de vida y estrategias de afrontamiento de pacientes con EHGNA en función de la diabetes tipo 2 y la obesidad, así como determinar qué estrategias de afrontamiento predicen la calidad de vida de estos pacientes. Para ello, en una muestra de 307 pacientes con EHGNA diagnosticada mediante biopsia hepática, fueron aplicados los cuestionarios Cuestionario de Salud SF-12, Cuestionario para pacientes con Enfermedad Hepática Crónica CLDQ-NAFLD y Cuestionario de Afrontamiento COPE-28. A continuación se realizaron pruebas estadísticas consistentes en análisis de la varianza y regresión lineal múltiple, para llegar a la conclusión de que los pacientes con diabetes u obesidad reportan una peor calidad de vida en comparación con aquellos sin patología metabólica comórbida y con la población general española. Los pacientes con obesidad también refieren un mayor empleo de estrategias de afrontamiento desadaptativas que aquellos sin obesidad. Finalmente, el estilo de afrontamiento activo se asocia con una mejor calidad de vida, mientras que el estilo pasivo/evitativo predice una peor calidad de vida en estos pacientes. Por último, en el sexto trabajo de esta Tesis Doctoral el objetivo fue determinar los biomarcadores psicológicos que ejercen un rol mediador o moderador en modelos predictores de la realización de actividad física y del seguimiento de una dieta mediterránea en pacientes con EHGNA. Para ello, se aplicaron los siguientes cuestionarios a una muestra de 413 pacientes con EHGNA diagnosticada mediante biopsia hepática: Cuestionario de Salud SF-12, Escala Hospitalaria de Ansiedad y Depresión, Escala de Autoeficacia General, Escala Multidimensional de Apoyo Social Percibido, Cuestionario Abreviado para Evaluación de Dieta Mediterránea MEDAS y Cuestionario Internacional de Actividad Física IPAQ. Luego fueron llevados a cabo análisis estadísticos basados en modelos de mediación moderada, que permitieron llegar a la conclusión de que tanto una pobre calidad de vida física como un bajo apoyo social se vinculan con una mayor sintomatología depresiva, lo que predice a su vez una menor adherencia terapéutica en los pacientes. En ambos casos, cuanto mayor es la autoeficacia, menor es el impacto negativo sobre la adherencia terapéutica, por lo que una elevada autoeficacia funciona como un factor protector para la realización de actividad física y la alimentación en pacientes con EHGNA con un perfil psicosocial de riesgo. Los biomarcadores psicológicos abordados en la presente Tesis Doctoral, es decir, calidad de vida, salud mental, estrategias de afrontamiento, autoeficacia y apoyo social, se han mostrado relevantes para predecir y contribuir al impacto en el funcionamiento físico, mental y social del paciente con EHGNA. Marcadores hepáticos y metabólicos como la fibrosis, la diabetes tipo 2 y la obesidad también han demostrado su influencia en el perfil biopsicosocial de estos pacientes. Por lo tanto, todos estos factores psicológicos, hepáticos y metabólicos deberían ser considerados en futuros tratamientos multidisciplinares de la EHGNA, lo que sugiere la integración de la evaluación e intervención psicológica en los protocolos de seguimiento de estos pacientes

Relationship Between Self-Perceived Health, Vitality, and Posttraumatic Growth in Liver Transplant Recipients

Our objective was to analyze the differences in posttraumatic growth in 240 liver transplant recipients based on two factors. First, self-perceived health: better (Group 1 = G1) and worse (Group 2 = G2). Second, vitality: more (Group 3 = G3) and less (Group 4 = G4). The Posttraumatic Growth Inventory, SF-36 Health Survey (Item 2) and SF-12 Health Survey (vitality dimension) were used. Firstly, analyzing main effects recipients with better (G1) compared to worse (G2) self-perceived health, showed greater posttraumatic growth. Interaction effects were found on essential posttraumatic growth domains such as new possibilities (p = 0.040), personal strength (p = 0.027), and appreciation of life (p = 0.014). Statistically significant differences showed that among transplant recipients with worse self-perceived health (G2), those with more vitality had higher levels on abovementioned posttraumatic growth dimensions. However, in transplant recipients with better self-perceived health (G1) respective dimensions were not significantly influenced by the level of vitality. Among the recipients with less vitality (G4), those with better self-perceived health showed higher scores on abovementioned posttraumatic growth dimensions. We conclude that positive self-perceived health might compensate for a lack of vitality as well as a high level of vitality may compensate for negative self-perceived health regarding the development of crucial aspects of posttraumatic growth after liver transplantation.Ministerio de Economía y Competitividad de España PSI2014-51950-

Psychological Biomarkers and Fibrosis: An Innovative Approach to Non-alcoholic Fatty Liver Disease

[Background] It is unknown how perceived social support and the progression of liver damage influence the psychosocial profile of patients with non-alcoholic fatty liver disease (NAFLD). In the present study, we therefore investigated which biomarkers influence the quality of life, mental health, and coping strategies of NAFLD patients.[Methods] Quality of life (SF-12 and CLDQ-NAFLD), mental health (HADS and BDI-II), and coping strategies (COPE-28) were evaluated by high or low perceived social support (MSPSS) and the presence of non-alcoholic steatohepatitis (NASH) and significant fibrosis in 492 biopsy-proven NAFLD patients. The results were compared with quality of life normality tables for the general Spanish population. We also determined whether liver histology and biopsychosocial variables predicted participants' quality of life.[Results] Interactive effects were found in vitality (p = 0.05), activity (p = 0.005), anxiety (p = 0.04), and denial (p = 0.04), with NASH patients showing a higher-risk biopsychosocial profile when they perceived less social support. Furthermore, patients with low perceived social support showed lower quality of life, worse mental health, and more maladaptive coping than those with high perceived social support, regardless of NASH presence. Patients with significant fibrosis showed lower quality of life compared to those without or the general Spanish population. Patients with significant fibrosis also reported worse mental health and more maladaptive coping. Lastly, significant fibrosis, female sex, greater anxiety and depressive symptoms, and worse physical and mental health-related quality of life were found to be independent determinants of worse disease-specific quality of life in these patients.[Conclusions] Low perceived social support, significant fibrosis, and female sex were independently associated with a higher-risk psychosocial profile in NAFLD. These findings support the role of psychological biomarkers based on quality of life, mental health, and coping strategies in the management of these patients and suggest the potential benefits of a psychological intervention.This study was funded by the Spanish Ministry of Economy, Industry and Competitiveness (Project PSI2017-83365-P), the Spanish Ministry of Education and Professional Training (Project FPU16/03146), and an unrestricted grant from Gilead Sciences, Inc

Influence of Psychological Biomarkers on Therapeutic Adherence by Patients with Non-Alcoholic Fatty Liver Disease: A Moderated Mediation Model

This article belongs to the Special Issue Nonalcoholic Fatty Liver Disease (NAFLD): Updates and Future Directions.Our aim was to analyze whether depressive symptoms mediated the association between physical quality of life (QoL) and adherence to physical activity in patients with non-alcoholic fatty liver disease (NAFLD), as well as the association between social support and adherence to diet. We also examined whether self-efficacy exerted a moderating role in these associations. QoL (SF-12), social support (MSPSS), depressive symptoms (HADS), self-efficacy (GSE), physical activity (IPAQ) and diet (MEDAS) were evaluated in 413 biopsy-proven NAFLD patients. Mediation and moderated mediation models were conducted using the SPSS PROCESS v3.5 macro. Results showed that depressive symptoms mediated the relationship between physical QoL and adherence to physical activity (indirect effect = 6.248, CI = 1.917–10.727), as well as the relationship between social support and adherence to diet (indirect effect = 0.148, CI = 0.035–0.275). Self-efficacy also moderated the indirect effects of QoL and social support on therapeutic adherence through depressive symptoms. Specifically, the higher self-efficacy was, the lower the negative impact on the NAFLD patient’s mental health. In conclusion, self-efficacy is defined as a protective factor for therapeutic adherence by NAFLD patients with a psychosocial risk profile. Self-efficacy should, therefore, be a main psychological target in future multidisciplinary NAFLD approaches.This research was funded by FEDER/Ministry of Science and Innovation—State Secretariat for Research (FEDER/Ministerio de Ciencia e Innovación—Agencia Estatal de Investigación), project PSI2017-83365-P; Ministry of Education and Professional Training (Ministerio de Educación y Formación Profesional), project FPU16/03146; Gilead Sciences, Inc., unrestricted grant

Vitality, mental health and role-physical mediate the influence of coping on depressive symptoms and self-efficacy in patients with non-alcoholic fatty liver disease: A cross-sectional study.

Our aim was to determine whether the association between active coping and depressive symptoms in patients with non-alcoholic fatty liver disease (NAFLD) was mediated by vitality, and whether diabetes and obesity could impact on this relationship. We also wanted to find out whether mental health and role-physical modulated the relationship between passive/avoidance coping and self-efficacy, and the role of liver fibrosis. Depressive symptoms (BDI-II), self-efficacy (GSE), coping (COPE-28) and quality of life (SF-12) were evaluated in 509 biopsy-proven NAFLD patients in this cross-sectional study. Mediation and moderated mediation models were conducted using the SPSS PROCESS v3.5 macro. Vitality mediated the relationship between active coping and depressive symptoms (-2.254, CI = -2.792 to -1.765), with diabetes (-0.043, p = 0.017) and body mass index (BMI) (-0.005, p = 0.009) moderating the association. In addition, mental health (-6.435, CI = -8.399 to -4.542) and role-physical (-1.137, CI = -2.141 to -0.315) mediated the relationship between passive/avoidance coping and self-efficacy, with fibrosis stage (0.367, p  A maladaptive coping style was associated with poorer vitality, mental health and role-physical in NAFLD patients, which along with the presence of metabolic comorbidity (diabetes and obesity) and significant fibrosis predicted more depressive symptoms or poorer self-efficacy in these patients. These results suggested incorporating emotional and cognitive evaluation and treatment in patients with NAFLD

Quality of Life and Coping in Nonalcoholic Fatty Liver Disease: Influence of Diabetes and Obesity

Our aim was to analyze how type 2 diabetes and obesity influence quality of life (QoL) and coping in patients with nonalcoholic fatty liver disease (NAFLD), and which coping strategies predict diabetic or obese participants’ QoL. QoL (SF-12, CLDQ-NAFLD) and coping strategies (COPE-28) were evaluated in 307 biopsy-proven NAFLD patients with absence or presence of diabetes or obesity. QoL was compared with normality tables for the general Spanish population. Interactive effects were found in physical functioning (p = 0.008), role-physical (p = 0.016) and activity (p = 0.014). Diabetic patients reported worse scores when they were also obese and vice versa, that is, obese patients scored worse when they were also diabetic. Both diabetic and obese patients had lower QoL than those without metabolic pathology or the general population, and obese patients also reported more passive/avoidance coping. Active coping, positive reframing and acceptance predicted better QoL, while denial, self-blame, self-distraction, disengagement and religion predicted lower QoL. In conclusion, diabetes and obesity were associated with lower QoL in patients with NAFLD. Obesity was also associated with more passive/avoidance coping. Furthermore, passive/avoidance coping strategies predicted lower QoL than active, recommending modification of maladaptive coping strategies in future multidisciplinary NAFLD treatments.FEDER/Ministerio de Ciencia e Innovación – Agencia Estatal de Investigación PSI2017-83365-PMinisterio de Educación y Formación Profesional FPU16/03146Gilead Sciences, Inc

Influence of Psychological Biomarkers on Therapeutic Adherence by Patients with Non-Alcoholic Fatty Liver Disease: A Moderated Mediation Model

Our aim was to analyze whether depressive symptoms mediated the association between physical quality of life (QoL) and adherence to physical activity in patients with non-alcoholic fatty liver disease (NAFLD), as well as the association between social support and adherence to diet. We also examined whether self-efficacy exerted a moderating role in these associations. QoL (SF-12), social support (MSPSS), depressive symptoms (HADS), self-efficacy (GSE), physical activity (IPAQ) and diet (MEDAS) were evaluated in 413 biopsy-proven NAFLD patients. Mediation and moderated mediation models were conducted using the SPSS PROCESS v3.5 macro. Results showed that depressive symptoms mediated the relationship between physical QoL and adherence to physical activity (indirect effect = 6.248, CI = 1.917–10.727), as well as the relationship between social support and adherence to diet (indirect effect = 0.148, CI = 0.035–0.275). Self-efficacy also moderated the indirect effects of QoL and social support on therapeutic adherence through depressive symptoms. Specifically, the higher self-efficacy was, the lower the negative impact on the NAFLD patient’s mental health. In conclusion, self-efficacy is defined as a protective factor for therapeutic adherence by NAFLD patients with a psychosocial risk profile. Self-efficacy should, therefore, be a main psychological target in future multidisciplinary NAFLD approaches.FEDER/Ministerio de Ciencia e Innovación PSI2017-83365-PMinisterio de Educación y Formación ProfesionalGilead Science

Relationship Between Self-Perceived Health, Vitality, and Posttraumatic Growth in Liver Transplant Recipients

Copyright © 2019 Funuyet-Salas, Martín-Rodríguez, Borda-Mas, Avargues-Navarro, Gómez-Bravo, Romero-Gómez, Conrad and Pérez-San-Gregorio.Our objective was to analyze the differences in posttraumatic growth in 240 liver transplant recipients based on two factors. First, self-perceived health: better (Group 1 = G1) and worse (Group 2 = G2). Second, vitality: more (Group 3 = G3) and less (Group 4 = G4). The Posttraumatic Growth Inventory, SF-36 Health Survey (Item 2) and SF-12 Health Survey (vitality dimension) were used. Firstly, analyzing main effects recipients with better (G1) compared to worse (G2) self-perceived health, showed greater posttraumatic growth. Interaction effects were found on essential posttraumatic growth domains such as new possibilities (p = 0.040), personal strength (p = 0.027), and appreciation of life (p = 0.014). Statistically significant differences showed that among transplant recipients with worse self-perceived health (G2), those with more vitality had higher levels on abovementioned posttraumatic growth dimensions. However, in transplant recipients with better self-perceived health (G1) respective dimensions were not significantly influenced by the level of vitality. Among the recipients with less vitality (G4), those with better self-perceived health showed higher scores on abovementioned posttraumatic growth dimensions. We conclude that positive self-perceived health might compensate for a lack of vitality as well as a high level of vitality may compensate for negative self-perceived health regarding the development of crucial aspects of posttraumatic growth after liver transplantation.This study was funded by the Spanish Ministry of Economy and Competitiveness (Project PSI2014-51950-P)

Health-related quality of life in non-alcoholic fatty liver disease: A cross-cultural study between Spain and the United Kingdom.

BACKGROUND: It is unclear what biopsychosocial factors influence the impact of NAFLD on health-related quality of life (HRQoL), and if these factors are equally important predictors between different nationalities. METHODS: HRQoL (CLDQ) was measured in both Southern European (Spain, n = 513) and Northern European (United Kingdom -UK-, n = 224) cohorts of patients with NAFLD in this cross-sectional study. For each cohort, participant data were recorded on histological grade of steatohepatitis, stage of fibrosis and biopsychosocial variables. Regression analysis was used to explore which of these variables predicted HRQoL. Moderated mediation models were conducted using SPSS PROCESS v3.5 macro. RESULTS: Participants with severe fibrosis reported more fatigue, systemic symptoms and worry, and lower HRQoL than those with none/mild fibrosis, regardless of place of origin. In addition, body mass index (BMI) and gender were found to be significant predictors of HRQoL in both Spanish and UK participants. Female gender was associated with worse emotional function, higher BMI and more fatigue, which predicted lower participants' HRQoL. UK participants showed more systemic symptoms and worry than Spanish participants, regardless of liver severity. The negative effects of gender on HRQoL through emotional function, BMI and fatigue were reported to a greater degree in UK than in Spanish participants. CONCLUSIONS: UK participants showed a greater impairment in HRQoL as compared to Spanish participants. Higher fibrosis stage predicted lower HRQoL, mainly in the Spanish cohort. Factors such as female gender or higher BMI contributed to the impact on HRQoL in both cohorts of patients and should be considered in future multinational intervention studies in NAFLD