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Despite the fact that non-alcoholic fatty liver disease (NAFLD) and its severe clinical forms [non-alcoholic steatohepatitis (NASH) and NASH-cirrhosis] are highly prevalent in the general population, there are no licensed drugs for NAFLD, and lifestyle intervention remains the only treatment accepted by international guidelines. This is despite massive investments in research by pharmaceutical companies. In the presence of type 2 diabetes, novel anti-diabetic drugs offer an opportunity to reduce the burden of NAFLD, by adequate control of glucose and lipid metabolism, also reducing the risk of NASH progression, advanced fibrosis, and finally hepatocellular carcinoma. We extensively reviewed the literature, based either on registration studies, ad hoc randomized studies or real-world data, to define the effectiveness of anti-diabetic drugs in the treatment of NAFLD and prevention of hepatocellular carcinoma (HCC). Metformin provides the best evidence for decreased risk of HCC, pioglitazone was associated with decreased progression to fibrosis, glucagon-like peptide-1 receptor agonists offer a possible opportunity to reduce NAFLD progression coupled with a definite protection for cardiovascular outcomes, and sodium-glucose cotransporter-2 inhibitors are likely to reduce lipid burden, simultaneously reducing the risk of progressive renal and heart failure. For the latter two drug classes, the effects on NAFLD might largely explained by decreased body weight, in keeping with the beneficial effects of intensive lifestyle intervention.

There has been a concerted effort to change the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD), and one wonders if it is appropriate and timely to bid adieu to the good old term. Numerous reasons have been put forth to justify this, as outlined in a recently published statement proposing the change. However, there are considerable flaws in the proposal, and changing NAFLD to MAFLD is unlikely to move the field forward.We have serious misgivings on this matter.o begin with, the statement by the MAFLD consensus group that the term NAFLD was coined by Ludwig and colleagues is factually incorrect. Although the histological features of NAFLD were first described decades ago, Klatskin and his colleagues, in 1979, were the first to use the term ‘non-alcoholic liver disease’.Later, while reporting similar findings, Ludwig and colleagues coined the term “non-alcoholic steatohepatitis (NASH)”.Although an association between metabolic syndrome (MS) and NAFLD has been established and NAFLD termed the hepatic manifestation of MS, this generalisation has since been questioned, since the complex heterogeneity of this entity precludes any single postulation to explain its pathogenesis. Besides, individuals with normal BMI also develop NAFLD, and studies in non-Caucasian populations have shown that a significant proportion of patients with NAFLD do not have insulin resistance (IR).Further, even with elevated hepatic triacylglycerol and diacylglycerol content, hepatic IR has not been observed in murine models,and dissociation of hepatic steatosis from IR has also been noted in a subset of individuals. Importantly, in subjects with PNPLA3 polymorphisms,steatosis occurs independently of IR and serum lipid concentration. Further, increased serum bile acid levels also seem to be independently associated with NASH in non-diabetics.NAFLD is also associated with gut dysbiosis independent of BMI and IR. Finally, “soft” drink consumption has also been linked to the development of fatty liver independent of obesity, diabetes and hyperlipidemia.and last but not least, cigarette smoking too has been found to be an independent risk factor in NAFLD progression. Thus it is clear that pathogenesis of NAFLD is multifactorial and complex, involving multiple and divergent pathways.In Medicine, a change of name of any disease has significant implications for both medical professionals and patients.The term ‘NAFLD’ aptly describes individuals who have fatty liver but neither consume significant amounts of alcohol nor had any other reason for fatty liver. Research in NAFLD to date has failed to pinpoint any factor as the sole cause for hepatic steatosis and NAFLD still encompasses a spectrum of disorders, metabolic syndrome being a part – maybe a major part – of that spectrum with a relatively barren treatment armamentarium. Will changing nomenclature address these concerns? We fear it might paradoxically misdirect therapeutics in the direction of MS alone which may ultimately turn out to be a red herring. The consensus group found multiple faults with the term NAFLD; these include: i) NAFLD is a disease of exclusion instead of being defined by inclusion, ii) NAFLD is a vastly heterogeneous entity and cannot be managed as one single condition and iii) patients with NAFLD do consume alcohol and the impact of alcohol, albeit in non-significant amounts, is under scrutiny. In Medicine, naming a disease through exclusion has been acceptable since time immemorial. Non-Hodgkin lymphoma encompasses vastly diverse malignancies and yet the terminology very effectively delineates those disorders from Hodgkin lymphoma. Regarding heterogeneity, it is not clear how a mere change of name would make the entity more homogeneous. If the word “metabolic” in MAFLD is meant as a reference to MS, it would be a rejection of much of the scientific evidence gathered on NAFLD pathogenesis. In contrast to the assertion of the proponents of MAFLD, who after splitting “nonalcoholic” into - ‘non’ and ‘alcoholic’, suggest that the word “non” trivializes the problem while the word “alcoholic” demeans the patient, we believe that the word ‘nonalcoholic’ does go a long way in destigmatizing the patient. The European Liver Patients Association (ELPA) is believed to have expressed displeasure with the term NAFLD to the European Commission in 2018, and suggested that a change in nomenclature was required. The degree of assertion and the rationale for such a suggestion are unclear; it is also unclear whether the diverse pathogenesis of NAFLD – especially in non-Caucasians – was considered in the decision. Further, an opinion on the impact of non-significant alcohol intake on hepatic steatosis is also unclear as acknowledged in the consensus statement. Notably, metabolic abnormalities and BMI are well described risk factors for alcoholic liver disease too,but it is unclear why both conditions more or less related to alcohol should be brought under the umbrella of MAFLD. The change of nomenclature has also been argued against since NAFLD is treated by cardiologists, diabetologists and primary care providers in addition to hepatologists; a name change could create unnecessary clinical confusion and coding issues. The heterogeneity of NAFLD and presence of multiple pathophysiological pathways inherent to its progression implies that the time is ripe to classify NAFLD in a novel way that takes into account the various pathophysiological processes. We wish to propose the ‘MEGA-D’ classification emphasising the ‘mega diversity’ or heterogeneity in NAFLD where NAFLD remains the umbrella entity with different subgroups under it (NAFLD-M: Metabolic syndrome associated NAFLD, NAFLD-E: Environmental Stressor Related NAFLD, NAFLD-G: Genetic Factor Associated NAFLD, NAFLD-A: Bile Acid Dysregulation Related NAFLD, NAFLD-D: Gut Dysbiosis Related NAFLD) representing separate pathways culminating in hepatic steatosis. We feel, instead of semantic juggling, collaborative efforts should be launched worldwide to better understand the vast heterogeneity in NAFLD across populations and ethnicities and explore its different pathophysiologic mechanisms, with the sole purpose of modifying disease progression, bolstering the treatment arsenal and curbing this epidemic.

Introduction: Fatty liver is rather common in pregnancy, occurring in two totally different conditions, i.e. nonalcoholic fatty liver disease (NAFLD) in pregnancy and acute fatty liver of pregnancy (AFLP). The former is a common condition, resulting by chance association because of the epidemics of obesity and the older age of many pregnant women in Western countries; the latter is a rare disease whose pathophysiology is still incompletely understood. Areas covered: We reviewed the evidence-based knowledge on fatty liver in/of pregnancy. For NAFLD, a few large retrospective and prospective studies identify immediate and late risks for both the mother and the fetus. For AFLP, only small retrospective studies are available, indicating that prompt delivery and eventual referral to Liver Units for liver support or transplantation are mandatory to avoid maternal and fetal death. Expert opinion: The number of pregnant women with fatty liver is expected to increase in the next years. Pharmacologic treatment of NAFLD might be postponed, even when new drugs are approved by health authorities for the general population. In the case of AFLP, we need to improve our ability to correctly identify and treat the most severe cases not resolving with delivery.

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Non-alcoholic fatty liver disease is a very common medical condition, driven by a combination of genetic and lifestyle factors, ultimately producing a severe chronic liver disease and increased cardiovascular risk. Most people are asymptomatic for a long time, and their daily life is unaffected, leading to difficulty in identifying and managing people who slowly progress to non-alcoholic steatohepatitis (NASH), NASH-cirrhosis, and eventually hepatocellular carcinoma. Despite advances in the understanding of pathogenic mechanisms and the identification of liver fibrosis as the strongest factor in predicting disease progression, no specific treatments have been approved by regulatory agencies. Outside controlled trials, treatment is generally limited to lifestyle intervention aimed at weight loss. Pioglitazone remains the drug of choice to reduce progression of fibrosis in people with diabetes, although it is often used off-label in the absence of diabetes. Vitamin E is mainly used in children and may be considered in adults without diabetes. Several drugs are under investigation according to the agreed targets of reduced NASH activity without worsening of fibrosis or improving fibrosis without worsening of NASH. Anti-inflammatory, anti-fibrotic agents and metabolism modulators have been tested in either phase III or phase IIb randomized controlled trials; a few failed, and others have produced marginally positive results, but only a few are being tested in extension studies. The development of non-invasive, easily repeatable surrogate biomarkers and/or imaging tools is crucial to facilitate clinical studies and limit liver biopsy.

Lutein is a carotenoid with reported anti-inflammatory properties. A large body of evidence shows that lutein has several beneficial effects, especially on eye health. In particular, lutein is known to improve or even prevent age-related macular disease which is the leading cause of blindness and vision impairment. Furthermore, many studies have reported that lutein may also have positive effects in different clinical conditions, thus ameliorating cognitive function, decreasing the risk of cancer, and improving measures of cardiovascular health. At present, the available data have been obtained from both observational studies investigating lutein intake with food, and a few intervention trials assessing the efficacy of lutein supplementation. In general, sustained lutein consumption, either through diet or supplementation, may contribute to reducing the burden of several chronic diseases. However, there are also conflicting data concerning lutein efficacy in inducing favorable effects on human health and there are no univocal data concerning the most appropriate dosage for daily lutein supplementation. Therefore, based on the most recent findings, this review will focus on lutein properties, dietary sources, usual intake, efficacy in human health, and toxicity.

Introduction: Following lifestyle intervention programs based on dietary restriction and habitual physical activity, weight loss, however large, is reported to peak within six months. Despite maintenance protocols, only few cases continue to lose weight thereafter. The majority of cases regain weight and adherence to lifestyle changes are fostered by long-term contact with a supportive team. In general, surgical procedures are reported to produce much larger weight loss and to impact more favorably on long-term weight loss maintenance. Areas covered: We performed a PubMed search on lifestyle modification studies, focusing on the role of behavior programs for the long-term management of obesity in comparison with surgical procedures. Behaviorally-achieved weight loss outcomes can be improved by integrating standard behavior therapy with self-regulation cognitive skills, motivational interviewing and/or phone/internet-based recall systems. Expert commentary: Clinically-important long-term weight loss is achievable by behavior therapy in a small proportion of subjects with obesity, however severe, through personalized programs associating lifestyle modification interventions, with procedures aimed at developing commitment and responsibility skills. A new area of research is the integration of cognitive-behavior therapy with bariatric (metabolic) surgery, either pre- or post-operatively, to exploit long-term adherence to healthy diet and habitual physical activity.

Purpose: We aimed to determine cognitive drivers, expected to play a role in target reach and/or attrition in obesity programs. Methods: We recorded the expected benefits of weight loss, weight targets, primary motivation for weight loss, perceived treatment needs, readiness and self-confidence to be successful and a battery of psychopathology questionnaires in 793 subjects with obesity (68% women; mean age 48.7; 46% obesity class III) enrolled into a group-based cognitive-behavioral treatment program. Their relevance on attrition and successful weight loss outcome were tested by logistic regression analysis. Results: The expected benefits of weight loss scored very high in all physical, psychological and social areas, with differences between genders. Attrition rate was 24, 41 and 65% at 6-, 12-, and 24-month follow-up. Average weight loss was 5.8 ± 7.1 kg (− 4.8%) at 6 months, with 17% of cases (32% of continuers) maintaining weight loss > 10% at 24 months. After adjustment for confounders, attrition was reduced by concern for present health, motivation/consciousness of the importance of physical activity and need for support; treatment discontinuation was favored by concern for body image, by expectations for drug treatment or bariatric surgery, and by high-challenging weight loss targets. Male gender, higher BMI and concern for present health predicted weight loss > 10%, whereas concern for body appearance was associated with lower probability of attaining the desired weight loss targets. Conclusion: A more precise definition of needs and expectations might help tailor treatment to individual patients, but attrition rates and target reach remain difficult to predict. Level of evidence: Level V, descriptive studies.

Objective: The analysis of the relation between weight loss goals and attrition in the treatment of obesity has produced conflicting results. The aim of the present study was to investigate the role of weight loss goals on attrition in a cohort of obese women seeking treatment at 8 Italian medical centres. Methods: 634 women with obesity, consecutively enrolled in weight loss programmes, were included in the study. Weight loss goals were evaluated with the Goals and Relative Weights Questionnaire (GRWQ), reporting a sequence of unrealistic (‘dream' and ‘happy') and more realistic (‘acceptable' and ‘disappointing') weight loss goals. Attrition was assessed at 12 months on the basis of patients' medical records. Results: At 12 months, 205/634 patients (32.3%) had interrupted their programme and were lost to follow-up. After adjustment for age, baseline weight, education and employment status, attrition was significantly associated with higher percent acceptable and disappointing weight loss targets, not with dream and happy weight loss. Conclusion: In ‘real world' clinical settings, only realistic expectations might favour attrition whenever too challenging, whereas unrealistic weight loss goals have no effect. Future studies should assess the effect of interventions aimed at coping with too challenging weight goals on attrition.

To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population.The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss10% in the last three-six months. Values of Malnutrition Universal Screening Tool (MUST)2, NRS-20023, and Mini Nutritional Assessment (MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases.A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition (OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients.More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.

Severe obesity is a chronic disease associated with medical and psychosocial comorbidity causing disability and poor quality of life that represents a social and economic burden for the National Health Systems worldwide. The Italian Society of Physical and Rehabilitation Medicine (SIMFER), the Italian Society of Obesity (SIO) and the Italian Society of Eating Disorders (SISDCA) have joined in a panel of experts to discuss a consensus document on the requisites of rehabilitation units devoted to patients affected by severe obesity with comorbidities. The main recommendations of the consensus document are the following: (1) the management of severe obesity should be characterized by the integration of nutritional, physical/functional rehabilitation, psycho-educational, and rehabilitative nursing interventions; (2) the intensity of the rehabilitative interventions should depend on the level of severity and comorbidities, frailty of the psychic status, degree of disability and quality of life of the patient; (3) the rehabilitative approach should be multidisciplinary and integrated in relation to the clinical complexity of obesity; (4) the estimated need for multidimensional rehabilitation of severe obesity is 1 bed per every 1,000 patients and of 4 beds in rehabilitative day-care ward every 1,000 patients suffering from severe obesity with comorbidities. © 2014 Springer International Publishing.

Purpose Anorexia (AN) and bulimia nervosa (BN) are two common eating disorders, which appear to share some reduced motor capacities, such as a reduced balance. The presence and the extent of other motor disorders have not been investigated in a comprehensive way. The aim of this study was to quantify gait pattern in AN and BN individuals in order to ascertain possible differences from the normality range and provide novel data for developing some evidence-based rehabilitation strategies. Methods Nineteen AN patients (age 30.16+9.73) and 20 BN patients (age 26.8+8.41) were assessed with quantitative 3d computerized Gait Analysis. Results were compared with a group of healthy controls (CG; 30.7+5.6). Results AN and BN patients were characterized by different gait strategies compared to CG. Spatio-temporal parameters indicated shorter step length, with AN showing the shortest values. AN walked slower than BN and CG. As for kinematics, AN and BN showed a nonphysiologic pattern at pelvis and hip level on the sagittal and frontal plane, with BN yielding the most abnormal values. Both AN and BN patients were characterized by high ankle plantar flexion capacity at toe-off when compared to CG. As for ankle kinetics, both AN and BN showed physiologic patterns. Stiffness at hip level was close to CG in both pathologic groups; at the ankle level, stiffness was significantly decreased in both groups, with AN displaying lower values. Conclusions Both AN and BN were characterized by an altered gait pattern compared to CG. Biomechanical differences were evident mainly at pelvis and hip level. Loss of lean mass may lead to musculoskeletal adaptation, ultimately causing alterations in the gait pattern.

Background: The economic and social costs of obesity are estimated to be considerable, particularly for inpatient care. The aim of this study was to compare the hospitalization rates of individuals with severe (body mass index [BMI] ≥40 kg/m§ssup§2§esup§) or complicated (BMI ≥30 kg/m§ssup§2§esup§) obesity with those of the general population in two regions of Northwest Italy, and to describe absolute costs of hospitalization and their determinants. Methods. Between 1996 and 2002, 6,516 patients who were admitted for the first time to a hospital offering a nutritional rehabilitation programme for obesity were enrolled and followed-up (mean follow-up time: 7.3 years). Standardized hospitalization rates (SHRs) were computed by sex for all-cause and cause-specific hospitalization. The general population of the two regions was used as the reference population. The annual cost of hospitalization was estimated for the study cohort only at the individual level, and its association with different determinants was assessed using a multivariable linear model for longitudinal data. Results: SHRs of the study cohort versus the general population increased for all-cause hospitalization (males: 3.53, 95% CI 3.45-3.61; females: 3.22, 95% CI 3.18-3.26) as well as for most obesity-related conditions. The absolute median annual cost of hospitalization was 2,436 euros for males and 2,293 euros for females. Older age at cohort enrolment, BMI ≥40 kg/m§ssup§2§esup§, waist circumference above the median (males: 1.26 metres; females: 1.13 metres), and the presence of co-morbidities, such as cardiovascular diseases, respiratory diseases, cancer, diseases of the musculoskeletal system and connective tissue, and mental disorders, significantly increased the absolute median annual costs of hospitalization. Conclusions: The economic consequences of high hospitalization rates in obese individuals are relevant. Reducing the occurrence of co-morbidities among obese persons may be one important goal, not only for clinical reasons, but also from a public health point of view. © 2013 Migliore et al.; licensee BioMed Central Ltd.

Background: Obesity increases the risk of many health complications such as hypertension, coronary heart disease and type 2 diabetes, needs long-lasting treatment for effective results and involves high public and private care-costs. Therefore, it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated. Information and communication technologies (ICT) can help clinicians to deliver treatment in a cost-effective and time-saving manner to a large number of obese individuals with co-morbidities. Objective: To examine ad interim effectiveness of a 12-month multidisciplinary telecare intervention for weight loss provided to obese patients with type 2 diabetes. Design, Setting, and Participants: A single-center randomized controlled trial (TECNOB study) started in December 2008. At present, 72 obese patients with type 2 diabetes have been recruited and randomly allocated to the TECNOB program (n=37) or to a control condition (n=39). However, only 34 participants have completed at least the 3-month follow-up and have been included in this ad interim analysis. 21 out of them have reached also the 6-month follow-up and 13 have achieved the end of the program. Study is still on-going. Intervention: All participants attended 1-month inpatient intensive program that involved individualized medical care, diet therapy, physical training and brief psychological counseling. At discharge, participants allocated to the TECNOB program were instructed to use a weight-loss web-site, a web-based videoconference tool, a dietary software installed into their cellular phones and an electronic armband measuring daily steps and energy expenditure. Main Outcome Measures: Weight and disordered eating-related behaviors and cognitions (EDI-2) at entry to hospital, at discharge from hospital, at 3,6 and 12 months. Results: Ad interim analysis of data from 34 participants showed no statistically significant difference between groups in weight change at any time-point. However, within-group analysis revealed significant reductions of initial weight at discharge from hospital, at 3 months, at 6 months but not at 12 months. Control group had higher scores in Interpersonal distrust at 12 months. Conclusion: This ad interim findings revealed that the effect of the inpatient treatment was high and probably overwhelmed the effect of the TECNOB intervention. Much statistical power and long-term follow-up may enhance the probability to detect the TECNOB effect over and above the great one exerted by the inpatient program. © Castelnuovo et al.

Background: To compare the mortality rate of obese patients treated by laparoscopic gastric banding (LAGB) with the mortality rate of matched obese patients observed at medical centers. The net effect of bariatric surgery on total mortality is still controversial. Gastric bypass has been shown to reduce the relative risk of death, but similar data with LABG are still lacking. Methods: The surgical series was composed of 821 patients with a body mass index (BMI) >40 kg/m2 consecutively treated with LAGB at Padova University, Italy. The reference group was composed of 821 gender-, age-, and BMI-matched patients selected from a sample of 4681 adults with a BMI >40 kg/m2 observed at 6 Italian medical centers not using surgical therapy. Results: The mean follow-up was 5.6 ± 1.9 and 7.2 ± 1.2 years in the surgical and reference group, respectively. The vital status was known in 97.6% of the surgical group (8 deaths) and in 97.4% of the reference group (36 deaths). In the surgical group, the percentage of excess weight loss was 39.8% ± 17.9% 1 year after LAGB and 37.2% ± 23.8% 5 years after LAGB. The rate of late revisional surgery was 12.2%. Survival was estimated using the Kaplan-Meier method, and the differences between the 2 groups were evaluated using the log-rank test. The survival rate was significantly greater in the surgical group (P = 0.0004). On multivariate Cox analysis, the 5-year relative risk of death in the surgical group, adjusted for gender, age, and baseline BMI, was 0.36 (95% confidence interval 0.16-0.80). Conclusion: LAGB was associated with a 0% operative mortality rate and 40% stable excess weight loss. LAGB patients had a 5-year 60% lower risk of death than comparable morbidly obese patients. © 2007 American Society for Metabolic and Bariatric Surgery.