Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut–liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.

Objective: To characterize cardiac structure and function and cardiac autonomic control in patients with subclinical and overt hyperthyroidism. Design: Thirty patients with subclinical hyperthyroidism and 30 with overt disease were selected from patients never previously treated for endocrinological disease in the outpatient clinic of our institution. Twenty normal individuals were studied as control group. Methods: Left ventricular structure and function and cardiac autonomic control were evaluated, respectively, by two-dimensional Doppler echocardiography and by 24-h Holter recording with heart rate variability analysis. Results: Patients with overt hyperthyroidism showed greater values of left ventricular end-diastolic volume P , 0X05 and left ventricular mass P , 0X05 than patients with subclinical disease. In addition, the mean velocity of left ventricular ®bre shortening P , 0X05 and left ventricular ejection fraction P , 0X05 were greater in patients with overt hyperthyroidism than in patients with subclinical disease. No difference in any of these parameters was detectable between normal subjects and patients with subclinical disease. The isovolumic relaxation period was shorter in patients with subclinical hyperthyroidism than in control individuals P , 0X05 and in patients with overt hyperthyroidism P , 0X05. As regards cardiac autonomic control, all time and frequency domain measures decreased progressively from control individuals to patients with subclinical hyperthyroidism and those with overt disease P , 0X001. Conclusions: Thyrotoxic patients show changes in left ventricular structure and increased echocardiographic indexes of myocardial contractility, whereas the only echocardiographic feature detectable in patients with subclinical hyperthyroidism is an increased velocity of left ventricular relaxation. Cardiac parasympathetic withdrawal is evident in patients with overt hyperthyroidism and in patients with subclinical disease.

Background and hypothesis: Alteration in sympathovagal balance may be a mechanism of increased cardiovascular mortality and sudden death of patients with anorexia nervosa. This study was undertaken to characterize cardiac autonomic control in patients with anorexia nervosa by means of heart rate variability analysis. Methods: Heart period variability by 24‐h Holter recording was evaluated in 13 young women with anorexia nervosa, 10 constitutionally thin women, and 10 women of normal weight. Results: High‐frequency power, a measure of parasympathetic modulation of heart rate, and all‐time domain measures of heart rate variability were higher in patients with anorexia nervosa than in thin women and in those of normal weight. Thin women showed lower values of total power and of most components of power spectrum. Conclusions: Our data demonstrate an increased vagal tone in young women with anorexia nervosa. The marked increase in parasympathetic activity, not in response to an increase in sympathetic activity, could be detrimental and may contribute to the higher cardiovascular mortality of these patients.