Anna Simona Sasdelli

Managing the combination of nonalcoholic fatty liver disease and metabolic syndrome

Introduction: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are part of the same metabolic defect, both having insulin resistance as the main pathogenic mechanism and sharing similar outcomes (i.e., cardiovascular and liver-related mortality). The prevalence of NAFLD is expected to rise, owing to the increasing worldwide prevalence of obesity and MetS; therefore, the identification of factors responsible for disease progression is essential to devise therapeutic strategies. Areas covered: The available and potential future treatments for NAFLD in combination with MetS are reviewed in this paper, following an extensive literature search and personal experience. Expert opinion: All NAFLD patients should be evaluated for their metabolic, cardiovascular and liver-related risk. Weight loss through lifestyle intervention remains the most comprehensive and safe treatment of NAFLD and associated MetS; however, > 50% of patients fail to achieve target weight loss. Pharmacologic treatment seems to be important for these patients and for NAFLD cases with more advanced liver disease. It temporarily reverses metabolic alterations, but liver disease progresses after the treatment is stopped. Although current treatments are unsatisfactory, new drugs have been proposed and a few innovative compounds are in the pipeline of pharmaceutical companies. Before pharmacologic treatment can be routinely recommended for NAFLD, long-term randomized trials are needed, along with assessments of the safety and benefits of drugs on proper histological outcomes or validated surrogate markers. The intensive control of individual features of MetS remains mandatory.

Screening for Bipolar Disorder Symptoms in Depressed Primary Care Attenders: Comparison between Mood Disorder Questionnaire and Hypomania Checklist (HCL-32).

Objective. To describe the prevalence of patients who screen positive for bipolar disorder (BD) symptoms in primary care comparing two screening instruments: Mood Disorders Questionnaire (MDQ) and Hypomania Checklist (HCL-32). Participants. Adult patients presenting to their primary care practitioners for any cause and reporting current depression symptoms or a depressive episode in the last 6 months. Methods. Subjects completed MDQ and HCL-32, and clinical diagnosis was assessed by a psychiatrist following DSM-IV criteria. Depressive symptoms were evaluated in a subgroup with the Patient Health Questionnaire (PHQ-9). Results. A total of 94 patients were approached to participate and 93 completed the survey. Among these, 8.9% screened positive with MDQ and 43.0% with HCL-32. MDQ positive had more likely features associated with BD: panic disorder and smoking habit (P < .05). The best test accuracy was performed by cut-off 5 for MDQ (sensitivity = .91; specificity = .67) and 15 for HCL-32 (sensitivity = .64; specificity = .57). Higher total score of PHQ-9 was related to higher total scores at the screening tests (P < .001). Conclusion. There is a significant prevalence of bipolar symptoms in primary care depressed patients. MDQ seems to have better accuracy and feasibility than HCL-32, features that fit well in the busy setting of primary care.

Anger rumination and aggressive behaviour in borderline personality disorder

BACKGROUND Emotional instability and dyscontrolled behaviours are central features in borderline personality disorder (BPD). Recently, some cognitive dysfunctional mechanisms, such as anger rumination, have been found to increase negative emotions and promote dyscontrolled behaviours. Even though rumination has consistently been linked to BPD traits in non-clinical samples, its relationship with problematic behaviour has yet to be established in a clinical population. AIM The purpose of the study was to explore the relationships between emotional dysregulation, anger rumination and aggression proneness in a clinical sample of patients with BPD. METHODS Enrolled patients with personality disorders (93 with BPD) completed a comprehensive assessment for personality disorder symptoms, anger rumination, emotional dysregulation and aggression proneness. RESULTS Anger rumination was found to significantly predict aggression proneness, over and above emotional dysregulation. Furthermore, both BPD diagnosis and anger rumination were significant predictors of aggression proneness. CONCLUSION Future research should examine whether clinical techniques aimed at reducing rumination are helpful for reducing aggressive and other dyscontrolled behaviours in treating patients with BPD.

Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction.

Background: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors). Key Messages: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain-containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease. Conclusions: A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies.

La famiglia del paziente con disturbo borderline di personalità: carico della malattia e interventi destinati ai caregiver

SUMMARY. Aim . The scientific literature focused on factors involved in the onset of borderline personality disorder (BPD) h as given a cen tral role to the families of these patients. The role of the family in understanding the disorder has gradually changed thanks to research that investigated the interaction of several factors in the development of this psychopathology. Recently, scientific literature on DBP has allowed to consider parents as no longer “responsible” for the development of the disorder, but as directly involved in interpersonal problems of pa tients and therefore a potential “ally” in the management of crisis. The aim of this study is to describe and quantify the family burden of BPD patients and browse specific interventions for the family of these patients. Methods. PubMed and PsycINFO have been used for review with the following keywords: “borderline personality disorder”, “family”, “psychopathology”, “burden”, “psychoeducation”, “caregiver”, “care taker”. Results. Studies on family burden of BPD patients are still few. Research shows that the family burden of BPD patients is compa rable with that of families of patients with schizophrenia. Clinical trials of interventions for caregivers of patients with BPD show that spe cific strategies can reduce the family burden and improve their self-efficacy. Discussion. Scientific literature highlights the relevance of prob lems of families with a BPD member and the importance of involving them in the treatment of these patients.

Functional lipidomics in patients on home parenteral nutrition: Effect of lipid emulsions

AIM To investigate the fatty acid-based functional lipidomics of patients on long-term home parenteral nutrition receiving different intravenous lipid emulsions. METHODS A cross-sectional comparative study was carried out on 3 groups of adults on home parenteral nutrition (HPN), receiving an HPN admixture containing an olive-soybean oil-based intravenous lipid emulsion (IVLE) (OO-IVLE; n = 15), a soybean- medium-chain triacylglycerol-olive-fish oil-based IVLE (SMOF-IVLE; n = 8) or HPN without IVLE (No-IVLE; n = 8) and 42 healthy controls (HCs). The inclusion criteria were: duration of HPN ≥ 3 mo, current HPN admixtures ≥ 2 mo and HPN infusions ≥ 2/wk. Blood samples were drawn 4-6 h after the discontinuation of the overnight HPN infusion. The functional lipidomics panel included: the red blood cell (RBC) fatty acid (FA) profile, molecular biomarkers [membrane fluidity: saturated/monounsaturated FA ratio = saturated fatty acid (SFA)/monounsaturated fatty acid (MUFA) index; inflammatory risk: n-6/n-3 polyunsaturated fatty acid (PUFA) ratio = n-6/n-3 index; cardiovascular risk: sum of n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) = n-3 index; free radical stress: sum of FA trans isomers = %trans index] and FA pathway enzyme activity estimate (delta-9-desaturase = D9D; delta-6-desaturase = D6D; delta-5-desaturase = D5D; elongase = ELO). Statistics were carried out using nonparametric tests. The amount of each FA was calculated as a percentage of the total FA content (relative%). RESULTS In the OO-IVLE group, the percentage of oleic acid in the RBCs was positively correlated with the weekly load of OO-IVLE (r = 0.540, P = 0.043). In the SMOF-IVLE cohort, the RBC membrane EPA and DHA were positively correlated with the daily amount of SMOF-IVLE (r = 0.751, P = 0.044) and the number of HPN infusions per week (r = 0.753; P = 0.046), respectively. The SMOF-IVLE group showed the highest EPA and DHA and the lowest arachidonic acid percentages (P < 0.001). The RBC membrane linoleic acid content was lower, and oleic and vaccenic acids were higher in all the HPN groups in comparison to the HCs. Vaccenic acid was positively correlated with the weekly HPN load of glucose in both the OO-IVLE (r = 0.716; P = 0.007) and the SMOF-IVLE (r = 0.732; P = 0.053) groups. The estimated activity of D9D was higher in all the HPN groups than in the HCs (P < 0.001). The estimated activity of D5D was lower in the SMOF-IVLE group than in the HCs (P = 0.013). The SFA/MUFA ratio was lower in all the HPN groups than in the HCs (P < 0.001). The n-6/n-3 index was lower and the n-3 index was higher in the SMOF-IVLE group in comparison to the HCs and to the other HPN groups (P < 0.001). The %trans index did not differ among the four groups. CONCLUSION The FA profile of IVLEs significantly influenced the cell membrane functional lipidomics. The amount of glucose in the HPN may play a relevant role, mediated by the insulin regulation of the FA pathway enzyme activities.

Aggressive behavior and self-harm in Borderline Personality Disorder: The role of impulsivity and emotion dysregulation in a sample of outpatients

Impulsivity has often been related to aggressive and self-mutilative behavior in Borderline Personality Disorder (BPD). Many authors focused on the key role of emotion dysregulation in explaining vulnerability to dysfunctional behavior in BPD in addition to trait impulsivity. Furthermore, recent works have shed light on a gap in empirical research concerning the specific mechanisms by which a lack of affective regulation produces aggression proneness. The purpose of the study was to investigate the role of impulsivity and emotion dysregulation in determining vulnerability to aggression and deliberate self-harm in a sample of BPD outpatients. Enrolled patients with BPD (N =79) completed a comprehensive assessment for personality disorder symptoms, trait impulsivity, emotional dysregulation, aggressive and self - mutilative behavior. Trait impulsivity significantly predicted both aggressive and self-mutilative proneness. Furthermore, emotion dysregulation was found significantly to account for the vulnerability to aggression and self-injury, in addition to the variance explained by impulsivity. In conclusion, these findings support evidence that emotion dysregulation plays an important role in increasing the risk of dysfunctional behavior in impulsive BPD individuals.

NAFLD-Associated Hepatocellular Carcinoma: a Threat to Patients with Metabolic Disorders

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and its prevalence is increasing in relation to the epidemics of obesity and type 2 diabetes mellitus, via non-alcoholic fatty liver disease (NAFLD). Unhealthy lifestyles associated with metabolic disorders are per se risk conditions for NAFLD progression, and specific gene polymorphisms may also favor oncogenesis, particularly in the presence of advanced fibrosis or cryptogenic cirrhosis. However, NAFLD-associated HCC may also develop in non-cirrhotic NAFLD and is frequently diagnosed at a more advanced tumor stage, compared with virus/alcohol-related HCC. This highlights the need for screening programs and long-term surveillance for earlier HCC detection in patients with metabolic risk factors, a policy hindered by the large number of cases at risk, with costs unaffordable by National health systems. New screening tools and cost-utility studies are eagerly awaited to develop more appropriate programs for early detection and treatment of NAFLD-associated HCC.

Anger and depressive ruminations as predictors of dysregulated behaviours in borderline personality disorder

BACKGROUND Anger and depressive ruminations have recently received empirical attention as processes related to borderline personality disorder (BPD). The Emotional Cascade Model (Selby, Anestis, & Joiner, 2008) suggests that negative affect (such as anger and sadness) may trigger rumination, which in turn may increase the duration and extent of negative affect, leading to dysregulated behaviours aimed at reducing such intense and unpleasant emotions. AIM The aim of this study is to explore the relationships between emotional dysregulation, anger and depressive ruminations, and their role in predicting dysregulated behaviours (such as aggression and self-harm) in a clinical sample of patients with BPD. METHODS Ninety-one patients with a diagnosis of BPD were recruited from three outpatient community mental health centres and asked to complete a comprehensive assessment for personality disorder symptoms, emotion dysregulation, anger and depressive ruminations, aggression, and self-harm. RESULTS Anger and depressive ruminations were found to be significantly associated to, respectively, self-harm and aggression, beyond the variance accounted by emotional dysregulation. CONCLUSIONS Rumination may act as a mediator between emotional dysregulation and dysregulated behaviours in BPD. Future research should examine whether clinical techniques aimed at reducing rumination may be helpful in reducing dysregulated behaviours in patients with BPD.

How Much Fat Does One Need to Eat to Get a Fatty Liver? A Dietary View of NAFLD

The prevalence of nonalcoholic fatty liver disease is increasing worldwide, and dietary habits have an important role in the epidemics of disease. High-fat diets are likely to contribute to hepatic triglyceride accumulation, and reducing dietary fat intake is recommended to prevent metabolic liver disease and liver disease progression to nonalcoholic steatohepatitis. However, also a diet rich in refined carbohydrates, i.e., simple sugars, and poor in dietary fibers may increase liver fat deposition, even more than dietary fats, through de novo lipogenesis. In conclusion, a hypercaloric diet, independently of macronutrient composition, drives hepatic fat accumulation, whereas a few fat sources, in particular monounsaturated fatty acids and polyunsaturated fatty acids present in olive oil and fish, may reduce the risk of steatosis or even cure fatty liver. Adherence to a Mediterranean dietary style, thanks to its high-fiber and antioxidant content, and lower fat intake remains the most favorable dietary intervention for the prevention and treatment of nonalcoholic fatty liver disease, mainly when coupled with habitual physical activity.