Sarcopenic Obesity in Liver Transplanted Patients

Study Overview
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Brief Summary
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The prevalence of obesity in cirrhotic patients who are candidates for liver transplantation (LT) is increasing, a phenomenon consistent with the increased prevalence of obesity in the general population. On the other hand, in liver patients on the waiting list for transplantation it is often observed sarcopenia. The combination of the two condition is defined sarcopenic obesity, which combines the negative synergy deriving from the two conditions. In this study the investigators will evaluate, for the first time, the prevalence of sarcopenic obesity in subjects undergone LT and determine the possible associated risk factors, particularly the role of immunosuppressive treatment with calcineurin inhibitors in addition to dietary habits and physical activity.

Detailed Description
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Obesity is a clinical condition characterized by excessive body weight due to the accumulation of adipose tissue, which represents a risk to health. In particular, obesity represents a risk factor for cardiovascular diseases, metabolic syndrome, NAFLD, and significantly increases the risk of mortality compared to normal weight subjects. It has been reported that the presence of obesity represents a risk factor for post-operative complications in patients undergone LT, increasing the mortality risk in those with the highest degree of obesity. At the same time, an evaluation obesity on the basis of body mass index (BMI) does not take in account the real body composition in terms of fat mass and muscle mass, which are more effective prognostic factors. Data of the literature report that patients undergoing liver transplantation (LT) have an average weight gain of 9 kg during the first year following the transplant, whereas in the second year, it would be observed about 24% incidence of obesity that would reach 30-38% in the third year. However, in all these studies the evaluation of de novo obesity is biased by the lack of data on the body weight of the patients prior their inclusion in the waiting list or to the use of dry body weight in patients mostly decompensated, or the loss of patients at the follow up. On the other hand, in liver patients on the waiting list for transplantation it is often observed sarcopenia, a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength associated with an increased risk of adverse events such as disability, poor quality of life and death. In this clinical setting, it has been reported in a percentage ranging from 41% to 68 %. The combination of the two condition defined sarcopenic obesity, which combines the negative synergy deriving from the two conditions, has been reported to be 20-40% in patients on the waiting list for liver transplantation. In addition, calcineurin inhibitors, which represent the backbone of anti-rejection therapy, have been investigated for their negative effect on muscle mass. In this study the investigators will evaluate, for the first time, the prevalence of sarcopenic obesity in subjects undergone LT and assess the possible associated risk factors, particularly the role of immunosuppressive treatment with calcineurin inhibitors (Ciclosporin and Tacrolimus), iin addition to dietary habits and physical activity. To achieve this goal the investigators will first screen all liver transplanted patients for muscle strenght and then all subjects with reduced muscle strenght will undergo bioelectrical impedance analysis (BIA). The presence of both conditions will allow us to identify subjects with sarcopenic obesity. Finally, the immunosuppressive therapy will be compared in liver transplanted patients with and without sarcopenic obesity. The evaluation of risk factors for obesity will be completing by the assessment of dietary habits and physical activity.

Official Title
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Sarcopenic Obesity and Associated Risk Factors in Patients Undergone Liver Transplant

Conditions
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Sarcopenic Obesity

Intervention / Treatment
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* Diagnostic Test: Evaluation of appendicular skeletal muscle mass (ASMM) by bioelectrical impedance analysis (BIA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients who have had a liver transplant for more than one year Exclusion Criteria: patients who have had a liver transplant for less than one year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| liver transplanted patients without sarcopenic obesity (controls)<br>All liver transplanted patients followed as outpatients at out clinic, which lack at least one of the two conditions (muscle strenght and muscle mass) used to identify sarcopenic obesity. | Diagnostic Test: Evaluation of appendicular skeletal muscle mass (ASMM) by bioelectrical impedance analysis (BIA)<br>* The use of handgrip dynamometer and BIA will be used to screen all liver transplanted patients for sarcopenic obesity, using a muscle strength cut-off <27 Kg in men and <16 Kg in women and a standardized muscle mass cut-off <0.789 ASMM/BMI for men and 0.512 ASMM/BMI for women.<br>* Other names: The Yale Food Addiction Scale will be used to exclude risk of patients to binge;|
| liver transplanted patients with sarcopenic obesity (cases)<br>All liver transplanted patients followed as outpatients at out clinic, with both muscle strenght and muscle mass. | Diagnostic Test: Evaluation of appendicular skeletal muscle mass (ASMM) by bioelectrical impedance analysis (BIA)<br>* The use of handgrip dynamometer and BIA will be used to screen all liver transplanted patients for sarcopenic obesity, using a muscle strength cut-off <27 Kg in men and <16 Kg in women and a standardized muscle mass cut-off <0.789 ASMM/BMI for men and 0.512 ASMM/BMI for women.<br>* Other names: The Yale Food Addiction Scale will be used to exclude risk of patients to binge;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sarcopenic obesity prevalence in liver transplanted patients | In all obese patients identified by a body mass index (BMI) ≥ 30 the investigators will first evaluate muscle strenght and those subjects with a reduction of muscle strenght (muscle strength <27 Kg in men and <16 Kg in women) will undergo the evaluation of muscle mass by bioelectrical impedance analysis; in the latter case the appendicular skeletal muscle mass (ASM) will be standardized for BMI (ASM/BMI), and the cut-offs considered will be <0.789 for men and <0.512 for women. | At enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The possible involvement of calcineurine inhibitors in patients with sarcopenic obesity | The investigators will compare the prevalence of sarcopenic obesity in subjects receiving calcineurin with that observed in subjects receiving other therapies by the Chi squared or Fisher test. In case of a significantly different prevalence between the two groups, a multivariate analysis will be performed to confirm if calcineurin inhibitor therapy is an indipendent risk factor for sarcopenic obesity. | At enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver transplantation, obesity, sarcopenia, calcineurin inhibitors