BRIEF REPORT

Associations between Liver Enzymes, Psychopathological and Clinical Features in Eating Disorders Lorenzo Lelli1, Giovanni Castellini1, Tommaso Gabbani2, Lucia Godini1, Francesco Rotella1 & Valdo Ricca1* 1 2

Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Firenze, Italy Gastroenterology 1, Department of Medical and Surgical Specialties, University of Florence, Firenze, Italy

Abstract Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently reported in patients with anorexia nervosa (AN) and in subjects who are overweight or with hyperlipidemia, which can be found to be associated with binge eating disorder (BED) and bulimia nervosa (BN). Liver functioning and psychopathological features have been evaluated in 43 patients with AN, 33 with BN, and 32 with BED. Body mass index was found to be inversely associated with AST and ALT in AN, and directly associated with AST and ALT in BED. A positive association between ALT and AST and body shape concern in AN was observed. Liver enzymes could be considered as an index of severity in AN and BED patients. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association. Keywords ALT; AST; BMI; eating disorders; psychopathology *Correspondence Valdo Ricca, MD, Psychiatric Unit, Department of Neuroscience, University of Florence, Largo Brambilla 3, 50134 Florence, Italy. Email: valdo.ricca@unifi.it Published online 19 August 2014 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/erv.2317

Introduction and aims

Method

Eating disorders (EDs) are characterized by a persistent disturbance of eating or eating-related behaviours that results (APA, 2013) in several medical complications related to the nutritional status (Miller et al., 2005; Winston, 2012). Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently reported in patients with anorexia nervosa (AN) (Montagnese et al., 2007), and they generally improve after refeeding and weight recovery (Dowman, Arulraj, & Chesner, 2010; Narayanan, Gaudiani, Harris, & Mehler, 2010). Moreover, abnormal serum levels of hepatic enzymes are frequently present in subjects who are overweight or with hyperlipidemia, which can be associated with binge eating disorder (BED) and bulimia nervosa (BN) (Bruckert et al., 2002), and ALT, AST and gamma-glutamyl transpeptidase (GGT) levels have been found to correlate with total body fat (Choi, 2003). As for many other serum levels alterations in EDs, liver enzymes fluctuation are usually asymptomatic, but they can disclose a compromised medical condition, which in some cases lead to a severe liver damage or failure (De Caprio et al., 2006; Di Pascoli, Lion, Milazzo, & Caregaro, 2004; Sakada et al., 2006). To our knowledge, no previous studies have compared hepatic enzyme profiles of the EDs diagnoses (AN, BN and BED), taking into consideration both medical parameters and psychopathological variables as possible correlates. Our hypothesis is that serum hepatic levels could represent a valid biomarker of EDs’ severity from both the medical and psychological perspective.

The study was planned and conducted at the Outpatient Clinic for Eating Disorders (EDs) of the Psychiatric Unit of the Department of Neuroscience, Psychology, Drug Research and Child Health of the University of Florence (Italy). Before the collection of data, during the first routine visit, the procedures of the study were fully explained, and the patients were asked to provide their written informed consent to the participation to the study. The study protocol was in accordance with the ethical standards of the responsible institutional committee. All patients attending for the first time to the Clinic for Eating Disorders of the University of Florence, between January 2013 and November 2013, were consecutively enrolled in the study, provided they met the following inclusion criteria: female gender, age between 18 and 60 years old, diagnosis of AN or BN or BED according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV assessed by means of the Structured Clinical Interview for DSM-IV (SCID-I/P) (First, Spitzer, Gibbon, & Williams, 1995). The exclusion criteria were as follows: alcohol abuse, use of medications (i.e. antipsychotics, carbamazepine and antibiotics) and/or recent illnesses (i.e. within the last 2 weeks before the enrollment) that could possibly increase liver enzyme levels, hepatitis due to viral or other causes, illiteracy, mental retardation, current comorbidity with schizophrenia, suicide ideation and psychoactive substance dependence. Nine patients chose not to participate, and 12 were deemed ineligible because of the following reasons: five patients had alcohol abuse, two patients had viral hepatitis, one patient had mental retardation, two patients had recent illness and two patients had cocaine abuse.

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The final sample was composed of 108 patients: 43 AN subjects (33 with restricting subtype; 10 with binge/purging subtype), 33 BN and 32 BED subjects. Study data included a medical history, abdominal echography, and anthropometric, psychopathological and laboratory measurements. The medical and psychiatric history was investigated by a gastroenterologist and a psychiatrist through a face-to-face interview. The body mass index (BMI) was calculated during the visits. The Structured Clinical Interview for DSM-IV (SCID-I/P) (First et al., 1995) was used in order to evaluate the presence of comorbid Axis I psychiatric disorders. The EDs’ general and specific psychopathological features were investigated by means of the following questionnaires: Eating Disorder Examination Questionnaire (EDE-Q) (Fairburn & Cooper, 1993), Emotional Eating Scale (Arnow, Kenardy, & Agras, 1995), Symptom Checklist (SCL 90-R) (Derogatis, Lipman, & Covi, 1973), Beck Depression Inventory (Beck & Steer, 1987) and State-trait Anxiety Inventory (Spielberg, Gorsuch, & Lushene, 1970). Routine blood samples were drawn in the morning (8 AM) after an overnight fast for determination of serum levels of AST, ALT, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase, cholinesterase, total and direct bilirubin, creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and fibrinogen. The normal range of these values were defined as AST between 15 and 37 U/L, ALT between 12 and 65 U/L, GGT > 85 U/L, alkaline phosphatase between 50 and 136 U/L, cholinesterase between 7000 and 19 000 U/L, total bilirubin > 1 mg/dL and direct bilirubin between 0 and 0.2 mg/dL, CPK > 215 U/L, LDH between 84 and 246 U/L and fibrinogen between 200 and 450 mg/dL.

Chi square (χ 2) and univariate analyses of variance with Bonferroni post hoc test were adopted to compare diagnostic groups (AN, BN and BED) for categorical and continuous variables, respectively. Pearson’s correlations and subsequently linear regression analyses (entering age and psychopathology as covariate) were performed in the whole sample, and within each group, to assess the associations between ALT, AST, GGT with BMI and other clinical variables.

Results All the 108 patients included in the study were at their first contact with the clinic and the mean (±standard deviation) ages on onset were 18.4 ± 3.3 for patients with AN, 19.2 ± 2.5 for patients with BN and 19.8 ± 7.3 for patients with BED. Eleven patients (10.2%) were taking low doses of benzodiazepines. As far as current psychiatric comorbidities are concerned, seven patients (6.5%) fulfilled the criteria for dysthymia, five (4.6%) for adjustment disorder with depressed mood, five (4.6%) for generalized anxiety disorder, three (2.8%) for panic disorder and two (1.8%) for obsessive compulsive disorder. The mean length of abnormal nutritional habits (i.e. restriction, binging or purging behaviours) was (mean ± SD) 12.8 ± 3.7, 10.1 ± 2.8 and 21.2 ± 7.7 for patients with AN, BN and BED, respectively. Data obtained from abdominal echography showed that 106 out of the 108 patients included in the study did not show any significant echographic alteration, whereas two patients with BED displayed steatosis. Clinical and psychopathological features of the three groups are reported in Table 1. Data are reported as mean ± standard deviation or number with percentages. As expected, BED patients showed a

Table 1 Body mass index, blood values and psychopathological variables in anorexia nervosa, bulimia nervosa and binge eating disorder

Age (years) 2 BMI (kg/m ) Fibrinogen (mg/dL) AST (U/L) ALT (U/L) CPK (U/L) LDH (U/L) GGT (U/L) ALP (U/L) Cholinesterase (U/L) Bilir tot (mg/dL) Bilir dir (mg/dL) SCL-GSI BDI STAI EDE-Q total score EDE restraint EDE eating concern EDE weight concern EDE shape concern EES

AN (n = 43)

BN (n = 33)

BED (n = 32)

F

Tukey b post hoc test

29.29 ± 11.65 15.76 ± 1.61 349.14 ± 85.66 30.6 ± 18.18 33.74 ± 26.45 115.31 ± 152.43 189.33 ± 60.27 20.84 ± 18.53 62.02 ± 26.13 5991.63 ± 1930 0.52 ± 0.30 0.17 ± 0.11 1.48 ± 0.81 22.41 ± 11.3 43.29 ± 25.59 2.89 ± 1.61 3.00 ± 2.12 2.48 ± 1.27 3.23 ± 1.6 3.39 ± 1.63 1.08 ± 0.86

27.61 ± 8.34 21.33 ± 2.44 389.22 ± 67.52 22.28 ± 8.95 21.78 ± 11.35 103.04 ± 97.19 169.73 ± 40.72 15.39 ± 9.38 62.77 ± 20.78 6408.6 ± 2136.6 0.47 ± 0.26 0.15 ± 0.08 1.41 ± 0.71 17.0 ± 8.45 6.82 ± 27.21 2.68 ± 1.57 2.90 ± 2.08 2.42 ± 1.53 2.83 ± 1.37 3.16 ± 1.93 3.04 ± 1.85

40.97 ± 13.39 39.41 ± 8.84 430.55 ± 113.86 23.11 ± 11.06 24.3 ± 16.45 104.15 ± 58.75 198.38 ± 52.13 18.52 ± 9.63 77.71 ± 26.62 7818.4 ± 1736.5 0.30 ± 0.33 0.14 ± 0.09 1.48 ± 0.75 19.75 ± 10.08 39.78 ± 25.25 2.95 ± 1.57 1.95 ± 1.73 2.65 ± 1.81 3.57 ± 1.8 3.97 ± 1.88 2.61 ± 1.33

13.58*** 189.06*** 5.39** 4.04* 3.61* 0.11 1.7 1.02 2.97 6.08** 5.25** 0.71 0.62 1.73 0.55 4.04* 3.72* 2.42 10.06*** 7.95 15.24***

BED > BN, AN BED > BN > AN BED, BN > AN AN > BED, BN AN, BED > BN

BED > AN, BN BED > AN, BN

AN, BN > BED

BED > BN > AN

AN, anorexia nervosa; BN, bulimia nervosa; BED, binge eating disorder; BMI, body mass index; AST, aspartate aminotransferase; ALT, alanine aminotransferase; CPK, creatine phosphokinase; LDH, lactate dehydrogenase; GGT, gamma-glutamyl transpeptidase; ALP, alkaline phosphatase; Bil tot, total bilirubin; Bilir dir, direct bilirubin; SCL-90 GSI, Symptom Checklist (SCL 90-R) Global Severity Index; BES, Binge Eating Scale; BDI, Beck Depression Inventory; STAI, State-trait Anxiety Inventory; EDE-Q, Eating Disorder Examination Questionnaire; EES, Emotional Eating Scale Total Score. Statistics—continuous variables are reported as mean ± standard deviation; ***p < 0.001; **p < 0.01; *p < 0.05.

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Figure 1. Relationship between transaminase levels, BMI and psychopathology. (A) Association between AST/ALT and BMI in the whole sample. Quadratic line interaction is the best fit for the association. (B) Association between ALT/AST and BMI, according to different diagnostic groups. AN showed an inverse association, whereas BED showed a positive association. No significant interaction for BN patients. (C) Association between AST/ALT and EDE-Q shape concern scores. Tables report the mentioned association age and BMI adjusted

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higher BMI as compared with BN, whereas AN patients showed the lowest BMI. No significant difference was found between the three groups, in terms of general psychopathology (SCL-90, Beck Depression Inventory and State-trait Anxiety Inventory) and in terms of EDE-Q total and subscale scores, with the exception of EDE-Q restraint, which was found to be higher in AN and BN, as compared with BED patients. As far as emotional eating is concerned, BED showed the highest values, and AN the lowest. Considering the biomarkers, AN patients showed higher AST and ALT levels as compared with BN and BED patients. BED patients showed higher fibrinogen compared with the other groups and higher ALT than the BN group. AN patients showed higher rate of over threshold AST and ALT levels (threshold 40 U/L) as compared with BN group (23.3% vs 3.6%, χ 2 = 5.01 p = 0.025; 27.9% vs 7.1%, χ 2 = 4.60 p = 0.032). Other comparisons were not significant. Pearson’s correlations showed that in AN patients, both AST and ALT levels were negatively correlated with BMI (r = 0.38; p = 0.017; r = 0.49; p = 0.001) and directly correlated with CPK (r = 0.75; p < 0.001; r = 0.52; p < 0.001), LDH (r = 0.68; p < 0.001; r = 0.55; p < 0.001), GGT (r = 0.71; p < 0.001; r = 0.63; p < 0.001), alkaline phosphatase (r = 0.55; p < 0.001; r = 61; p < 0.001), direct bilirubin (r = 0.57; p < 0.001; r = 0.44; p = 0.001), and EDE-Q total (r = 0.30; p = 0.045; r = 0.31; p = 0.042) and shape concern scores (r = 0.41; p = 0.006; r = 0.51; p < 0.001). Among BN patients, AST and ALT levels were directly correlated with LDH (r = 0.77; p < 0.001; r = 0.63; p = 0.001) and GGT (r = 0.58; p = 0.003; r = 0.56; p = 0.01), and AST with direct bilirubin (r = 0.53; p = 0.004). Considering BED patients, AST and ALT levels were directly correlated with BMI (r = 0.45; p = 0.007; r = 0.57; p < 0.001) and LDH (r = 0.85; p < 0.001; r = 0.48; p = 0.026), whereas ALT only was directly correlated with GGT (r = 0.44; p = 0.043) and cholinesterase (r = 0.60; p = 0.004). Figure 1A reports the association between BMI and ALT and AST in the whole sample. The association between BMI and transaminase was almost described by a U-shaped curve, with a significant quadratic relationship. When the association was broken down according to the diagnostic groups (AN, BN and BED), BMI resulted to be inversely associated with AST and ALT in AN, directly associated with AST and ALT in BED, whereas no significant association was found between BMI and transaminase in BN (Figure 1B). The results of ALT association were confirmed for both AN (β = 0.41; p = 0.01) and BED (β = 0.58; p < 0.001), even when adjusting for age and EDE-Q scores. Finally, a significant association was found between AST and ALT levels and EDE-Q total and EDE-Q shape concern scores. When adjusting for age and BMI, shape concern and BMI retained their significance for both AST and ALT (Figure 1C).

Discussion The present study confirmed that AN and BED patients showed alterations in AST and ALT levels as compared with normal

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Conflict of interest The authors declare no conflict of interest.

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Associations between liver enzymes, psychopathological and clinical features in eating disorders.

Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently reported in patients with anorexia nervosa (AN) and...
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