In recent decades, overweight and obesity have become a global public health issue. Overweight and obesity are associated with increased risks of all-cause mortality, cancer, non-alcoholic fatty liver disease, hypertension, type 2 diabetes, and metabolic syndrome [1]. The major impact of obesity on the liver is the association with nonalcoholic steatohepatitis (NASH). Indeed, NASH has emerged as one of the fastest growing indications for liver transplantation [2].

Clinical observations in long-term survivors after liver transplantation have revealed a considerable gain in body weight and an increasing prevalence of obesity [1,3]. Most of the excessive weight gain occurs in the first year of transplantation and among the causes include recovery of the appetite followed by health improvement and hyperphagia associated to the corticosteroid use and a sedentary life style [4]. At the end of the first year after liver transplantation, patients fail to replenish their total body protein, while fat mass approximates predicted values [3]. Immunosuppressive medication is often cited as a risk factor for weight gain [1].

Recently, post-transplant obesity has received interest as part of the metabolic syndrome evolving after transplantation, jeopardizing the gain in patient prognosis achieved by transplantation [2,3]. Obesity is associated with metabolic disorders and comorbidities such as coronary artery disease [2]. Moreover, cardiovascular events have been reported as a leading cause of mortality after solid organ transplantation [1].

Considering this scenario and the importance of preventing obesity in liver graft survivors, nutritional status should be monitored in all post-transplant patients, leading to appropriate nutritional treatment. The aim of the present study was to evaluate the nutritional status of post-liver transplant patients.

The present study reports partial data from a major unpublished study of liver transplantation from our group conducted at Hospital das Clínicas, Ribeirão Preto Medical School, Sao Paulo University (HC-FMRP / USP) between March 2012 and December 2013. Nutritional status was assessed by body composition and anthropometric methods.

The sample consisted of a group of post-liver transplantation patients (n = 28) and a control group of patients without liver disease (n = 23).

The post-transplant group consisted of patients aged ≥ 18 years with a post-liver transplantation period > 30 days. Exclusion criteria were chronic kidney disease, acute or chronic respiratory failure, infectious pulmonary disease, untreated hyperthyroidism or hypothyroidism, and locomotor disability. The post-transplant group was divided into two subgroups according to post-transplant period, i.e., < 1 year and ≥ 1 year.

The control group consisted of outpatients aged ≥ 18 years seen at the Urology Clinic of HCFMRP-USP, matched to the post-transplant patients for gender, age and body mass index (BMI). Eligibility criteria included absence of alcohol consumption and of acute or chronic liver disease, renal failure, pulmonary disease, cancer, hyperthyroidism, hypothyroidism, and locomotor disability. Biochemical analyses of albumin, aminotransferases, total protein, cholinesterase, lactate dehydrogenase, bilirubin, alkaline phosphatase and glutamyl transferase were carried out according to standard methodologies [5-12] at the Laboratory of the Surgery Department, HCFMRP-USP, in order to determine liver function.

Anthropometric measurements of weight, height, arm and abdominal circumferences and skinfold thickness were performed for nutritional assessment. Measurements were made according to standard methods using calibrated equipment. BMI (weight/height²) was classified according to standard references for adults [13] and elderly subjects [14]. Arm muscle circumference, arm muscle area and arm fat area were assessed by equations and considered to represent malnutrition, normal weight and obesity according to reference values for gender and age [15-18].

Body composition was assessed by single frequency (50 kHz) electric bioimpedance using a Biodynamic Analyzer 310 model (Biodynamics Corporation, Seattle, WA, USA) for the tetrapolar method and using an Ironman Segmental Compositor BC-558 (Tanita Corporation, Toquio, Japan) for the segmental method, according to standard methods and with the patient fasted for at least 4 hours.

Food consumption was assessed by a trained dietitian using a habitual food record.

Statistical analyses were performed using the Prism GraphPad 4.0 software (San diego, CA, USA). Data are reported as mean and standard deviation for continuous quantitative variables. The Student t test and ANOVA (with Bonferroni’s post-test) were used to compare two or more independent groups. The chi-square test was applied to categorical variables. The level of significance was set at 5% in all tests.

The study was approved by the Ethics Committee HCFMRP-USP and all subjects gave written informed consent to participate.

Antropometric data are shown in Table 1. Mean muscle arm circumference (p = 0.0233) and mean muscle arm area (p = 0.0195) differed statistically between groups. A higher frequency of muscle mass defect (Figures 1 and 2) was observed in the < 1 year posttransplant group regarding muscle arm circumference and muscle arm area. Figure 3 shows the risk of disease according to waist circumference. Subscapular skinfold thickness differed significantly between groups (p = 0.0310).

Table 1: Anthropometric assessment of post-transplant patients. Data are reported as mean and standard deviation. ^a comparing ≥ 1 year posttransplant and <1 year post-transplant. ^b comparing ≥ 1 year post-transplant and control group.^ccomparing <1 year post-transplant and control group. BMI: Body mass index. AC: Arm circumference. MAC: Muscle arm circumference. AFA: arm fat area. MAA: muscle arm area. AbC: Abdominal circumference. BST: Biceps skinfold thickness. TST: Triceps skinfold thickness. SST: Subscapular skinfold thickness. IST: iliac skinfold thickness.

Figure 1: Nutritional status of the post-transplant and control groups according to muscle arm circumference. *p=0.002 for malnutrition between groups and p=0.0059 for normal weight between groups.

Figure 2: Nutritional status of the post-transplant and control groups according to muscle arm area. *p=0.0019 for malnutrition between groups.

Figure 3: Disease risk according to waist circumference in post-liver transplant patients.

Tetra polar bioelectrical impedance data are presented in Table 2 and segmental bioelectrical impedance data are presented in Table 3. There was no significant difference in body fat mass or body fat-free mass between groups according to both the tetra polar and segmental methods. Phase angle was significantly lower in the < 1 year posttransplant group.

Table 2: Tetrapolar bioelectrical impedance of patients. Data are reported as mean and standard deviation. ^acomparing ≥ 1 year posttransplant and <1 year post-transplant. ^bcomparing ≥ 1 year posttransplant and control group. ^ccomparing <1 year post-transplant and control group.

Table 3: Segmental bioelectrical impedance of the patients. Data are reported as mean and standard deviation.

Table 4 shows the energy and macronutrient intake, which did not differ significantly between groups.

Table 4: Energy and nutrient intake of the patients. Data are reported as mean and standard deviation. ^acomparing ≥ 1 year post-transplant and < 1 year post-transplant. ^bcomparing ≥ 1 year post-transplant and control group. ^ccomparing < 1 year post-transplant and control group.

The present study contributed important results to the literature by corroborating with recent findings about the nutritional status of liver transplant recipients.

Body mass index values indicating overweight and obesity were observed in liver transplant patients regardless of post-liver transplantation period. Excessive weight gain (more than 10 kg) during the first year after liver transplantation has been reported [1], with a 40% incidence of obesity in this population in the first posttransplant year [19] and an incidence of about 70% three years after transplantation [20,21].

Waist circumference was greater than the value recommended by the WHO [22], of 94 cm for men and 80 cm for women, in 78% of < 1 year post-transplant patients and in 79% of ≥ 1 year post-transplant patients. Among patients with overweight and obesity after a transplant period ≥ 1 year, waist circumference demonstrated higher severe risks of cardiovascular events according to the WHO classification [22].

Metabolic syndrome is characterized by impaired glucose tolerance, diabetes mellitus, and/or insulin resistance, with two or more factors such as abdominal obesity, elevated blood pressure, increased plasma triglycerides and micro albuminuria [22].

Studies have described an increased prevalence of dyslipidemia, hypertension and diabetes mellitus in liver transplant recipients. Together with the excessive body weight, these conditions contribute to the occurrence of metabolic syndrome and the increasing risk of cardiovascular events, which are the main cause of death after transplantation [23,24].

Although the difference was not significant, fat body mass was greater in patients with ≥ 1 year of liver transplantation, while lean body mass was similar for the two groups. In addition, overweight was diagnosed by measurement of arm circumference and arm fat area in 21% of ≥ 1 year post-transplant patients, while there was no diagnosis of overweight in < 1 year post-transplant group considering these anthropometric measures. Based on these findings, it seems that the recovery of body mass does not occur proportionally between fat and lean mass.

Increased food intake, physical inactivity and immunosuppressive therapy have been described as possible causes of obesity in liver transplant patients [7].

Phase angle, a measure of bioimpedance analysis, was similar between patients with a longer post-transplant period and controls, while patients with a shorter post-transplant period had a lower mean phase angle. These results suggest a full recovery from surgery and improved health after transplantation since phase angle is a measure associated with nutritional status and prognosis [25].

In conclusion, although the post-liver transplantation population studied here may have had a full recovery and health improvement after surgery, obesity and excessive fat body mass are prevalent and may be deleterious in the long term considering the associated risk of cardiovascular events.

The author’s responsibilities were as follows - Silva MA: accountable for research execution and manuscript preparation. Junior AAJ: accountable for research supervision and revision of the manuscript. Junior OCS: mentor of the research, accountable for research supervision and revision of the manuscript. This work was supported financially by a Capes Federal grant.

The authors declare that they have no conflict of interest.