Clinical and Histological Long-Term Follow-Up of De Novo HBV-Infection after Liver Transplantation.

Background and Objectives: Development of hepatitis-B is considered a serious complication after liver transplantation. HBV de novo infection is a rather rare phenomenon, however it deserves attention in the era of donor organ shortage. The aim of the present analysis was to examine its course in liver transplant patients. Materials and Methods: Prevalence of de novo HBV-infections was extracted from our local transplant data base. Analysis focused on the moment of HBV-detection and on the long-term follow-up in terms of biochemical and histological changes over 30 years. Results: 46 patients were identified with the diagnosis of de novo hepatitis B. Median time from liver transplantation to diagnosis was 397 days (7-5505). 39 patients received antiviral therapy. No fibrosis progression could be detected, whereas the grade of inflammation significantly lessened from the moment of HBV detection to the end of histological follow-up over a median of 4344 days (range 123-9490). Patients with a poor virological control demonstrated a significantly poorer overall survival. Conclusions: De novo hepatitis B in liver transplant patients is a condition that can be controlled very well without significant fibrosis progression or graft loss if recognized on time within a regular transplant follow-up schedule.

Circulating Neuronatin Levels Are Positively Associated with BMI and Body Fat Mass but Not with Psychological Parameters.

Human genetic studies have associated Neuronatin gene variants with anorexia nervosa (AN) and obesity. Studies on the expression of the Neuronatin gene product, a proteolipid, are lacking. We investigated the relationship between circulating Neuronatin, body mass index (BMI), body composition (BC), physical activity (PA), and psychometric outcomes in patients with AN, normal weight, and obesity. Plasma Neuronatin was measured by ELISA in (1) 79 subjects of five BMI categories (AN/BMI < 17.5 kg/m2; normal weight/BMI 18.5-25 kg/m2; obesity/BMI 30-40 kg/m2; obesity/BMI 40-50 kg/m2; obesity/BMI > 50 kg/m2) with assessment of BC (bioimpedance analysis; BIA); (2) 49 women with AN (BMI 14.5 ± 1.8 kg/m2) with measurements of BC (BIA) and PA (accelerometry); (3) 79 women with obesity (BMI 48.8 ± 7.8 kg/m2) with measurements of anxiety (GAD-7), stress (PSQ-20), depression (PHQ-9) and eating behavior (EDI-2). Overall, a positive correlation was found between Neuronatin and BMI (p = 0.006) as well as total fat mass (FM; p = 0.036). In AN, Neuronatin did not correlate with BMI, FM, or PA (p > 0.05); no correlations were found between Neuronatin and psychometric outcomes in obesity (p > 0.05). The findings suggest an FM-dependent peripheral Neuronatin expression. The decreased Neuronatin expression in AN provides evidence that Neuronatin is implicated in the pathogenesis of eating disorders.

NUCB2/nesfatin-1 in the acute stress response of obese women with high and low anxiety.

NUCB2/nesfatin-1 is an anorexigenic peptide hormone first known for its effects on energy homeostasis. More recently, a growing evidence suggests a role of NUCB2/nesfatin-1 in emotion regulation, particularly in the modulation of anxiety, depression and emotional stress response. Since stress-related mood disorders are often comorbid with obesity, we investigated the effect of acute psychosocial stress on circulating NUCB2/nesfatin-1 in obese women and normal-weight controls and its association with symptoms of anxiety. Forty women, 20 obese and 20 normal-weight controls, (aged between 27 and 46 years) were exposed to the Trier Social Stress Test (TSST). We assessed changes of plasma NUCB2/nesfatin-1, salivary cortisol, heart rate and subjective emotional state. Symptoms of anxiety (GAD-7), depressiveness (PHQ-9), perceived stress (PSQ-20), disordered eating (EDE-Q, EDI-2) and health-related quality of life (SF-8) were measured psychometrically. Obese women were further subdivided in a high and low anxiety group. Women with obesity displayed higher psychopathology compared to normal-weight controls. The TSST induced a biological and psychological stress response in both groups (p < 0.001). In normal-weight controls NUCB2/nesfatin-1 increased in response to stress (p = 0.011) and decreased during recovery (p < 0.050), while in obese women only the decrease during recovery was significant (p = 0.002). Obese women with high anxiety displayed higher NUCB2/nesfatin-1 levels than those in the low anxiety group (TSST: +34 %, p = 0.008; control condition: +52 %, p = 0.013). Our data substantiate the involvement of NUCB2/nesfatin-1 in the modulation of stress and anxiety. It remains unclear whether the attenuated stress response in obese subjects is due to metabolic changes or mental comorbidity.

Emotional stress responsivity of patients with IBS - a systematic review.

OBJECTIVE: Irritable bowel syndrome (IBS) is a highly prevalent disorder of the gut-brain interaction characterized by abdominal discomfort and pain associated with altered bowel habits in the absence of structural abnormalities. Chronic psychological stress is considered a risk factor for the development of IBS. The multifactorial pathogenesis involves complex interactions between biological, psychological and social factors, yet the underlying mechanisms have not been fully understood. METHODS: We systematically reviewed the literature from the databases MEDLINE, Embase and PsycINFO to assess stress responsivity of patients with IBS in comparison to healthy individuals, specifically focusing acute psychological stressors. RESULTS: A total of 37 case-control studies were included in the narrative synthesis. Findings comprised subjective changes in emotion (k = 18) and of gastrointestinal symptoms (k = 8) as well as objective parameters of gastrointestinal motility (k = 10), autonomic nervous system (k = 23), hypothalamic-pituitary-adrenal axis (k = 11), functional brain activity (k = 7) and immune system (k = 3). Mental stress was found to increase IBS-specific symptomatology and alter gastrointestinal motility. Some patients with IBS showed stress-induced emotional hyperresponsivity and different patterns of neural activation. Autonomic and endocrine stress responses depend on the type of stressor and showed no clear evidence of differential reactivity, partly due to confounding factors. Data on acute immunological changes remains sparse and requires further investigation. CONCLUSIONS: Current evidence suggests altered stress reactivity in patients with IBS however, it remains unclear whether it can be attributed to the syndrome itself or the high prevalence of psychiatric comorbidities.

Circulating Spexin Is Associated with Body Mass Index and Fat Mass but Not with Physical Activity and Psychological Parameters in Women across a Broad Body Weight Spectrum.

Spexin (SPX) is a novel, widely expressed peptide, with anorexigenic effects demonstrated in animal models and negatively correlated with body mass index (BMI) in humans. It increases locomotor activity in rodents and is elevated in human plasma following exercise. Studies have also shown an effect of stress and anxiety on SPX's expression in different brain structures in animals. The relationships between plasma SPX and physical activity, body composition, and patient-reported outcomes such as perceived stress, depressiveness, anxiety, and eating behaviors are unknown and were examined in this study over a wide BMI range. A total of 219 female (n = 68 with anorexia nervosa; n = 79 with obesity; n = 72 with normal weight) inpatients were enrolled. Perceived stress (PSQ 20), anxiety (GAD 7), depressiveness (PHQ 9), and eating disorder pathology (EDI 2), as well as BMI, bioimpedance analysis, and accelerometry, were measured cross-sectionally at the beginning of treatment and correlated with plasma SPX levels (measured by ELISA) obtained at the same time. Plasma SPX levels were negatively associated with BMI (r = −0.149, p = 0.027) and body fat mass (r = −0.149, p = 0.04), but did not correlate with perceived stress, anxiety, depressiveness, eating behavior, energy expenditure, and physical activity (p > 0.05). The results replicate the negative correlation of SPX with BMI and fat mass, but do not support the hypothesis that peripheral SPX plays a role in the regulation of stress, depressiveness, anxiety, eating behavior, or physical activity.

Neurotensin and Xenin Show Positive Correlations With Perceived Stress, Anxiety, Depressiveness and Eating Disorder Symptoms in Female Obese Patients.

OBJECTIVE: Neurotensin and xenin are two closely related anorexigenic neuropeptides synthesized in the small intestine that exert diverse peripheral and central functions. Both act via the neurotensin-1-receptor. In animal models of obesity reduced central concentrations of these peptides have been found. Dysregulations of the acute and chronic stress response are associated with development and maintenance of obesity. Until now, associations of both peptides with stress, anxiety, depressiveness, and eating disorder symptoms have not been investigated. The aim of the present study was to examine associations of neurotensin and xenin with these psychological characteristics under conditions of obesity. MATERIALS AND METHODS: From 2010 to 2016 we consecutively enrolled 160 inpatients (63 men and 97 women), admitted due to obesity and its mental and somatic comorbidities. Blood withdrawal und psychometric tests (PSQ-20, GAD-7, PHQ-9, and EDI-2) occurred within one week after admission. We measured levels of neurotensin and xenin in plasma by ELISA. RESULTS: Mean body mass index was 47.2 ± 9.5 kg/m2. Concentrations of neurotensin and xenin positively correlated with each other (women: r = 0.788, p < 0.001; men: r = 0.731, p < 0.001) and did not significantly differ between sexes (p > 0.05). Women generally displayed higher psychometric values than men (PSQ-20: 58.2 ± 21.7 vs. 47.0 ± 20.8, p = 0.002; GAD-7: 9.7 ± 5.8 vs. 7.1 ± 5.3, p = 0.004; PHQ-9: 11.6 ± 6.6 vs. 8.8 ± 5.9, p = 0.008; EDI-2: 50.5 ± 12.8 vs. 39.7 ± 11.9, p < 0.001). Only women showed positive correlations of both neuropeptides with stress (neurotensin: r = 0.231, p = 0.023; xenin: r = 0.254, p = 0.013), anxiety (neurotensin: r = 0.265, p = 0.009; xenin: r = 0.257, p = 0.012), depressiveness (neurotensin: r = 0.281, p = 0.006; xenin: r = 0.241, p = 0.019) and eating disorder symptoms (neurotensin: r = 0.276, p = 0.007; xenin: r = 0.26, p = 0.011), whereas, men did not (p > 0.05). CONCLUSION: Neurotensin and xenin plasma levels of female obese patients are positively correlated with perceived stress, anxiety, depressiveness, and eating disorder symptoms. These associations could be influenced by higher prevalence of mental disorders in women and by sex hormones. In men, no correlations were observed, which points toward a sex-dependent regulation.

Pancreatic Polypeptide but Not Other Members of the Neuropeptide Y Family Shows a Moderate Association With Perceived Anxiety in Obese Men.

Neuropeptide Y (NPY), peptide tyrosine tyrosine (PYY), and pancreatic polypeptide (PP) are important mediators in the bidirectional communication along the gut-brain-axis. Best known for their role in the regulation of appetite and food intake they are considered to play a crucial role in the development of obesity. Additionally, mounting evidence indicates a regulatory function in anxiety, mood and stress resilience with potential sex differences. In the present study, we examined the associations of NPY, PYY, and PP plasma levels with anxiety, depressiveness and perceived stress in obese patients. We analyzed 144 inpatients (90 female, 54 male, BMI mean: 49.4 kg/m2) in a naturalistic treatment setting for obesity and its somatic and mental comorbidities. Fasting blood samples were taken, and patients completed psychometric self-assessment questionnaires (GAD-7, PHQ-9, PSQ-20) within the first week after admission and before discharge. Plasma concentrations of the peptides were measured by ELISA. Women showed significant higher anxiety (GAD-7: 8.13 ± 5.67 vs. 5.93 ± 5.42, p = 0.04) and stress scores (PSQ-20: 52.62 ± 23.5 vs. 41.23 ± 22.53, p = 0.01) than men. In the longitudinal analysis women with a clinically relevant improvement of anxiety (≥ 5 points on GAD-7, p < 0.001) also showed significant improvements in depression (PHQ-9: 38%, p = 0.002) and PSQ-20 scores (23%, p = 0.005) while anxiety-improved male patients only improved in the subscale tension of the PSQ-20 (34%, p = 0.02). In men we observed a positive correlation of PP with anxiety scores (GAD-7: r = 0.41, p = 0.007) and with age (r = 0.49, p = 0.001) on admission while NPY negatively correlated with age (r = -0.38, p = 0.01). In contrast, there were no significant associations (p > 0.05) in female subjects in the cross-sectional as well as in the longitudinal analysis. In conclusion, women suffering from morbid obesity showed greater psychological comorbidity and considerable interactions among them. Despite that we solely observed associations of PP with anxiety and age with NPY and PP in men, suggesting a possible influence of sex hormones on the NPY system. However, improvement of anxiety scores did not lead to significant changes in NPY.