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Background: There is no consensus on the treatment of pediatric nonalcoholic fatty liver disease (NAFLD). However, in a small pilot study conducted in 10 children, metformin has been proposed to be effective. Objective: We aimed to determine the effect of metformin in addition to lifestyle intervention/modification in children with NAFLD. Methods: Overweight or obese children aged 9 to 18 years with biopsy-proven NAFLD or nonalcoholic steatohepatitis were enrolled in an observational pilot study, initially planned for 12 months, which aimed to estimate the effect of metformin on liver enzymes. The study was extended to 24 months to estimate outcomes on liver histology. All subjects received lifestyle intervention (nutritional counseling and a physical exercise regimen) and metformin 1.5 g/d (MET group). To serve as the control in this study, we selected a control group from a separate but parallel study (N = 30) that had identical inclusion criteria on the use of antioxidants in NAFLD. End points were changes in liver enzymes and histology. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment of IR (HOMA-IR) and liver biopsy was determined by the NAFLD activity score (NAS). Results: Sixty patients were assessed for inclusion in this study. However, 2 patients in the MET group dropped out of the study during the first year because they relocated abroad, and 1 patient in the control group refused follow-up after 12 months. Thus, study data is based on the findings in the 57 remaining patients. Alanine aminotransferase significantly improved from baseline with decreasing body weight in both groups (MET: 35 [range, 21–43] to 32 [20–46] U/L; control: 66 [28–121] to 33 [14–45] U/L; P ≤ 0.01). HOMA-IR significantly improved in both groups from baseline with decreasing body weight as well (MET: 1.4 [range, 0.5–5.11] to 1.3 [0.13–4.21]; control: 2.29 [0.86–5.76] to 1.5 [0.70–4.23]; P ≤ 0.01). Steatosis was reduced in both the MET (P = 0.02) and control (P = 0.02) groups as well as ballooning (both, P = 0.008). Lobular inflammation improved from baseline in the MET group (P = 0.003). The NAS score decreased from baseline (both, P = 0.001), but no significant changes in fibrosis were detected. Conclusion: In this small, 24-month observational study, metformin did not appear more effective than lifestyle intervention in ameliorating levels of aminotransferases, steatosis, and liver histology in these children with NAFLD.

Background It is uncertain whether patients with nonalcoholic fatty liver disease (NAFLD) and normal alanine aminotransferase (ALT) have a milder disease and should undergo liver biopsy. Materials & Methods We reviewed the histological data of 458 Italian patients with NAFLD in whom liver biopsy was indicated because of altered liver enzymes (395 cases, 86%) or persistently elevated ferritin or long-lasting severe steatosis in (63 cases). Factors associated with nonalcoholic steatohepatitis (NASH) and fibrosis ≥ 2 were identified by logistic regression analysis. Results Patients with normal ALT were significantly older, had lower body mass index, fasting triglycerides, insulin resistance (homeostasis model assessment – HOMA), ALT and gamma-glutamyltransferase (GGT), but a higher prevalence of hypertension. NASH was diagnosed in 59% and 74% patients with normal and increased ALT, respectively (p=0.01). In the overall series of patients, NASH was independently predicted by ALT (Odd Ratio (OR), 1.11; 95% confidence interval (CI), 1.04-1.19 per 10 IU/mL increase) and diabetes (OR, 1.5; 95% CI 1.1-2.0). The same variables were selected in patients with increased ALT, whereas in those with normal ALT, HOMA-IR and ALT were independent predictors. Severe fibrosis was independently predicted by serum ferritin (OR, 1.04; 95%CI 1.001-1.08 per 50 ng/mL increase), ALT (OR, 1.07; 95% CI1.02-1.14), and diabetes (OR, 1.8; 95%CI 1.4-2.3) in the overall series, serum ferritin and diabetes in those with increased ALT, and only HOMA-IR (OR, 1.97;95% CI 1.2-3.7) in patients with normal ALT. Conclusion Alterations in glucose metabolism and insulin resistance should be considered in the selection of NAFLD cases for the histological assessment of disease severity and progression, also in subjects with normal ALT.

Context In the last few years several data have accumulated suggesting that obesity may be associated with liver disease and disease progression. Accordingly, the worldwide epidemics of obesity is likely to become a relevant source of morbidity and mortality in the general population. Evidence Acquisition We reviewed the literature on two main issues: a) the evidence that obesity carries out an increased risk of liver disease, both in the general population and in selected cohorts; b) the evidence that obesity is risk factor for nonalcoholic fatty liver disease and its progression in series observed in Liver Units. Evidence Synthesis The presence of obesity increases the risk of elevated liver enzymes by a factor of 2-3, whereas the risk of steatosis at ultrasonography is increased by a factor of 3 in the presence of overweight and peaked at a factor of approximately 15 in the presence of obesity. Both cirrhosis (cryptogenic cirrhosis) and hepatocellular carcinoma are also associated with obesity in the general population. In patients with nonalcoholic fatty liver disease observed in liver units, obesity and weight gain are systematically associated with advanced fibrosis and fibrosis progression. Conclusion Liver disease of metabolic origin, associated with obesity, is now recognized as the most prevalent liver disease in Western countries. Strategies are needed to approach obesity-associated liver disease by behavior programs, motivating people to adopt a healthier lifestyle. Such programs should be coupled with public policies at societal level to obtain the maximum effects in lifestyle changes.

Objective: We aimed to investigate the association of the clinical variables of the metabolic syndrome (MS) and psychological parameters on health-related quality of life (HRQL) in obesity. In particular, our aim was to investigate the relative impact of physical symptoms, somatic diseases and psychological distress on both the physical and the mental domains of HRQL. Design: Cross-sectional study Subjects: 1822 obese outpatients seeking treatment in medical centers. Measurements: HRQL was measured by the standardized summary scores for physical (PCS) and mental (MCS) components of the Short Form 36 Health Survey (SF36). Patients were grouped according to tertiles of PCS and MCS. The profiles of individual components of MS and the psychological status in the various tertiles were compared by discriminant analysis. Results: The profile of metabolic and psychological variables was tertile-specific in 62.4% and 68.3% of patients in the lowest and highest tertiles of PCS, respectively, while concordance was low in the mid tertile (32.8%). Concordance was very high in the lowest (74.4%) and in the highest (75.5%) tertile of MCS, and was fair in the mid tertile (53.2%). The main correlates of PCS were obesity-specific and general psychological well-being, BMI, body uneasiness, binge eating, gender and psychiatric distress. Only raised blood pressure and glucose qualified as correlates among the components of MS. The components of MS did not define MCS. Conclusions: Psychological well-being is the most important correlate of HRQL in obesity, both in the physical and in the mental domains, whereas the features of MS correlate only to some extent with the physical domain of HRQL.

In the dictionary, fast food is defined as any food which may be cooked easily, and is sold by restaurants to be eaten quickly or taken away. Changes in the dietary pattern of the last decades have made fast food a relevant component of western diet, but a diet largely based on fast food has detrimental effects on health, which have been a matter of discussion for 20 years.1 Two potential mechanisms have been suggested: a) fast feeding does not suppress appetite, leading to increased calorie consumption; b) fast food is usually richer in fats and saturated fats (and thus richer in calories), as well as in other components which may cause harm to several organs, namely widespread cardiovascular disease. Both mechanisms are likely to promote obesity, but is there evidence for a direct hepatotoxicity? The issue came to public attention in the movie “Super Size Me”. After consuming three meals a day in a fast food restaurant for one month, Morgan Spurlock increased by nearly 10 kg, and liver enzymes peaked at 290 U/L (alanine aminotransferase - ALT) from baseline values of 20 U/L, accompanied by increased total cholesterol, uric acid and the onset of clinical features of the metabolic syndrome. No doubt that elevated aminotransferase levels are a marker of hepatic dysfunction, but are they related to any specific dietary component of fast food-based diet, or simply to weight gain and obesity-associated non-alcoholic fatty liver disease (NAFLD)?

Objective: Body image dissatisfaction is common in treatment-seeking patients with obesity. We aimed to investigate the effects of obesity management on body image in patients with obesity attending Italian medical centers for weight loss programs. Research Methods and Procedures: A total of 473 obese patients seeking treatment in 13 Italian medical centers (80% females; age, 45.9 ± standard deviation 11.0 years; BMI, 36.8 ± 5.7 kg/m2) were evaluated at baseline and after a 6-month weight loss treatment. Body uneasiness, psychiatric distress, and binge eating were tested by Body Uneasiness Test (BUT, Part A), Symptom CheckList-90 (SCL-90), and Binge Eating Scale (BES), respectively. Results: At 6-month follow-up, the percentage weight loss was significantly higher in men (9.0 ± 6.3%) than in women (6.8 ± 7.3%; p = 0.010). Both men and women had a significant improvement in BUT Global Severity Index and in all of the BUT subscales with the exception of the Compulsive Self-Monitoring subscale. Linear regression analysis selected baseline psychological and behavioral measures (global score of BUT and SCL-90) and improved psychiatric distress and binge eating as independent predictors of changes in basal body dissatisfaction in females, whereas in males, changes were associated only with baseline BUT-Global Severity Index score, binge eating, and its treatment-associated improvement. Pre-treatment BMI and BMI changes did not enter the regression. Discussion: Obesity treatment, even with a modest degree of weight loss, is associated with a significant improvement of body image, in both females and males. This effect depends mainly on psychological factors, not on the amount of weight loss.

BACKGROUND: Insulin resistance is a significant risk factor for hepatic fibrosis in patients with both non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC), either directly or by favouring hepatic steatosis. Several methods are available to assess insulin resistance, but their impact on this issue has never been evaluated. AIMS: To determine the relative contribution of steatosis, metabolic abnormalities and insulin resistance, measured by different basal and post-load parameters, to hepatic fibrosis in CHC and in NAFLD patients. METHODS: In 90 patients with CHC and 90 pair-matched patients with NAFLD, the degree of basal insulin resistance (by the homeostasis model assessment, (HOMA)) and post-load insulin sensitivity (by the oral glucose insulin sensitivity (OGIS) index) was assessed, together with the features of the metabolic syndrome according to Adult Treatment Panel III definition. Data were correlated with hepatic histopathology. RESULTS: The prevalence of basal insulin resistance (HOMA values >75th percentile of normal) was 23.3% in CHC patients and 57.8% in NAFLD, but it increased to 28.8 and 67.8% when measured by post-load insulin resistance (OGIS

La steatosi epatica non alcolica [Nonalcoholic Fatty Liver Disease (NAFLD)] è attualmente la più comune epatopatia nei paesi occidentali con prevalenza in costante aumento. Essa rappresenta uno spettro di epatopatie comprendenti la steatosi semplice e la steatoepatite [Non alcoholic Steatohepatitis (NASH)] con possibile evoluzione verso la fibrosi epatica, cirrosi ed epatocarcinoma. L’associazione clinica con le malattie metaboliche, soprattutto nelle NAFLD più aggressive, suggerisce un ruolo eziopatogenetico dell’insulino- resistenza. La prognosi dipende dal grado di fibrosi e necroinfiammazione; i pazienti con statosi semplice sembrano essere scarsamente evolutivi, mentre la NASH con o senza fibrosi, identifica un gruppo di pazienti a rischio di evoluzione del danno epatico. I test di laboratorio e le metodiche di immagine non consentono né la differenziazione tra steatosi pura e NASH, né la stadiazione della patologia epatica. Si rende quindi indispensabile la biopsia epatica, il cui impiego razionale è guidato dal rischio di danno epatico severo. La modificazione dello stile di vita finalizzata alla correzione della sedentarietà e dell’obesità viscerale è da considerarsi tutt’oggi il principale strumento di prevenzione e trattamento della NAFLD. Per quanto riguarda il trattamento farmacologico, sebbene esistano evidenze sull’utilità di diversi agenti in piccoli gruppi di pazienti, la mancanza di studi randomizzati controllati sufficientemente numerosi e di sufficiente durata, basati su rilievi istologici, rende oggi difficile fornire raccomandazioni terapeutiche definitive.

• Liver biopsy remains the only diagnostic tool to stage NAFLD and to assess disease progression; clinical/biochemical parameters may be used as surrogate markers, but their accuracy is limited • The presence of multiple features of the metabolic syndrome is associated with more advanced and more progressive disease • Obesity and diabetes are associated with more aggressive liver disease, but their effect on final outcome is uncertain • Cardiovascular risk may compete with liver disease-related risk in dictating the final outcome • Longitudinal studies based on liver biopsy data are needed to define the natural history of disease

OBJECTIVE: To investigate the psychometric properties of the Body Uneasiness Test (BUT) in a large sample of subjects with obesity seeking treatment. BUT is a 71-item self-report questionnaire in two parts: BUT-A which measures weight phobia, body image concerns, avoidance, compulsive self-monitoring, detachment and estrangement feelings towards one's own body (depersonalization); and BUT-B, which looks at specific worries about particular body parts or functions. METHODS: We recruited a clinical sample of 1,812 adult subjects (age range 18-65 years, females 1,411, males 401) with obesity (Body Mass Index, BMI > or = 30 kg/m2) and a normal weight (BMI value between 18.5 and 25 kg/m2) non-clinical sample of 457 adult subjects (females 248, males 209) with an Eating Attitudes Test-26 (EAT-26) score under the cut-off point 20 (scores > or = 20 indicate possible cases of eating disorders). RESULTS: The exploratory and confirmatory analyses confirmed a structural five-factor model for BUT-A and an eight-factor model for BUT-B. Internal consistency was satisfactory. Concurrent validity with Binge Eating Scale (BES) and Three-Factor Eating Questionnaire (TFEQ) was evaluated. The authors calculated mean values for BUT scores in adult (18-65 years) patients with obesity, and evaluated the influence of gender, age and BMI. Females obtained statistically significant higher scores than males in all age groups and in all classes of obesity; patients with obesity, compared with normal weight subjects, generally obtained statistically significant higher scores, but few differences could be attributed to the influence of BMI. CONCLUSION: The BUT can be a valuable multidimensional tool for the clinical assessment of body uneasiness in obesity; the scores of its sub-scales do not show a linear correlation with BMI values.

Personality traits seem to have an important role in the development, course, and treatment response in eating disorders. We investigated the effects of an inpatient cognitive behavioral treatment (CBT) on the measures of temperament and character (Temperament and Character Inventory - TCI) in 149 patients with eating disorders (ED). Baseline assessment included anthropometry, the Eating Disorder Examination (EDE), the Beck Depression Inventory (BDI), and the TCI. Treatment lasted 20 weeks (in-hospital, 13 weeks; residential day-hospital, 7) and was based on the transdiagnostic cognitive behavior theory and treatment of ED, adapted for inpatient setting. Treatment effects were tested by paired ANOVA, adjusted for covariates. No effects were found on Novelty Seeking, Reward Dependence, and Cooperativeness. Harm Avoidance (F =18.17, p

Objectives. Hyperferritinemia is frequently observed in NAFLD, the hepatic manifestation of the metabolic syndrome characterized by hepatic insulin resistance and considered at high cardiovascular risk. Iron depletion by phlebotomy has been reported to decrease insulin resistance in NAFLD in small, uncontrolled studies. Aims of this study were to define the relationship between ferritin and iron stores in patients with NAFLD, the effect of iron depletion on insulin resistance, and whether basal ferritin levels influence treatment outcome. Methods. Subjects were included if ferritin and/or ALT were persistently elevated after 4 months of standard therapy. Sixty-four phlebotomized subjects were matched 1:1 for age, sex, ferritin, obesity, and ALT levels with patients who underwent lifestyle modifications only. Insulin resistance was evaluated by insulin levels, determined by RIA, and the HOMA-R index, at baseline and after 8 months. Results. Baseline ferritin levels were associated with body iron stores (p=0.006). Iron depletion resulted in a significantly larger decrease in insulin resistance (p=0.0002 for insulin, p=0.0007 for HOMA-R) compared with nutritional counseling alone, independently of changes in BMI, baseline HOMA-R, and the presence of the metabolic syndrome. Iron depletion was more effective in reducing HOMA-R in patients in the top two tertiles of ferritin concentrations (p

In the last few years several clinical and epidemiological studies have convincingly associated nonalcoholic fatty liver with the metabolic syndrome, having insulin resistance as the pivotal pathogenic factor. Obesity, type 2 diabetes mellitus, dyslipidemia and hypertension differently contribute to an increased risk of liver disease, and to disease progression. The presence of multiple metabolic abnormalities is associated with the severity of liver disease, namely with the fibrosis characterizing nonalcoholic steatohepatitis, with cryptogenic cirrhosis and finally with hepatocellular carcinoma. These subjects have a high risk of cardiovascular morbidity and mortality, mediated by early atherosclerosis. This evidence has precise therapeutic implications: only a behavior approach to lifestyle correction will simultaneously address all the alterations characterizing the metabolic syndrome, including metabolic liver disease.

La NAFLD (Non-Alcoholic Fatty Liver Disease – Steatosi epatica non alcolica) è una condizione clinica di comune riscontro che comprende un ampio spettro di patologie epatiche che vanno dalla semplice steatosi, a prognosi generalmente benigna, a quadri più avanzati come la steatoepatite (NASH, Non-Alcoholic Steatohepatitis), caratterizzata da necroinfiammazione e fibrosi di vario grado, fino ad arrivare alla cirrosi criptogenetica ed al carcinoma epato-cellulare. Dal punto di vista anatomo-patologico, si caratterizza per una quadro simile alla steatosi alcol-indotta, ma si sviluppa in soggetti il cui consumo di alcol è nulla o molto modesto (il limite è arbitrariamente fissato a 20-30 g di alcol al giorno).

Nonalcoholic fatty liver disease (NAFLD) defines the most of common liver diseases encompassing alcohol-like hepatic histologic lesions seen in the non-alcoholic insulin resistant patient. NAFLD, deemed to be the hepatic counterpart of the metabolic syndrome, represents a multifactorial condition spanning the widespectrum from steatosis through non-alcoholic steatohepatitis (NASH) with or without (cryptogenic) cirrhosis. End-stage liver failure and hepatocellular carcinoma are observed in a yet undetermined proportion of individuals. Along with insulin resistance, additional endocrine and vascular changes play a prominent role in the development and progression of NAFLD. Genetic factors underlying NAFLD are being unravelled. Their understanding will further our understanding of pathogenesis and will also probably enhance non-invasive diagnosis. Diet and physical exercise represent, with the correction of predisposing metabolic changes, the mainstay of treatment. Insulin sensitizing drugs should better be used only in selected patients, preferably in the context of controlled clinical trials. Non-invasive evaluation of risk for cardiovascular events is recommended in all individuals presenting with NAFLD and conversely, the presence of NAFLD should be always looked for in subjects with features belonging to the metabolic syndrome.

To investigate the construct validity of the Short Form-36 (SF-36) Health Survey questionnaire in obese patients.Our series consisted of 1735 obese patients (age, 44.7 +/- 11.0 years; 1346 women) consecutively enrolled in the QUOVADIS study, an observational multicenter study of obese treatment-seeking outpatients. The construct validity of the SF-36 was assessed by main component analysis. Age-, gender-, and education-adjusted general linear models were used to investigate the relationship between BMI and SF-36 domains or factors identified by main component analysis.BMI was significantly associated with poor health-related quality of life in all eight SF-36 domains, and the strongest association was observed with physical activity. Main components analysis generated a six-factor solution explaining 59% of the observed variance. BMI was strongly associated with factors based on the loading of items regarding the physical activity domain and factors based on role-physical and role-emotional items or general health and bodily pain items. In contrast, mental health-, vitality-, and social functioning-based factors were not related to BMI.In obese treatment-seeking outpatients, the clustering of SF-36 items in main components is not significantly different from the domain-based approach generally used, thus confirming the robustness of such a generic questionnaire in this specific condition. However, the peculiar clustering of some SF-36 items and their relationship with BMI suggest that the health-related quality of life profile of subjects belonging to that population may be better described with alternative aggregations of the SF-36 items or with disease-tailored questionnaires.

OBJECTIVE: Both arterial hypertension and chronic hepatitis are common disorders. The relationship between arterial pressure and liver cirrhosis has been extensively studied, but no studies are available in chronic hepatitis (CH). Recently, a few studies have reported that treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs), commonly used in arterial hypertension, reduce hepatic fibrosis in patients with viral CH and in nonalcoholic steatohepatitis. This study was aimed at comparing the evolution of post-viral CH in patients with/without concomitant essential hypertension. Methods: Two sets of observations were carried out: a) a cross-sectional cohort study of 95 patients with viral CH, to compare the severity of histological and biochemical data at diagnosis, in relation to pharmacologically-treated essential hypertension; and b) a retrospective study with the observation of 254 patients with CH of viral etiology, followed up from 2 to 20 years, to establish the natural history of viral CH in relation to treated essential hypertension. Results: In the cross-sectional analysis, patients with treated hypertension had a significantly older age at diagnosis of CH (51.4 ± 8.4 years vs. 46.2 ± 12.2 in normotensive; P

BACKGROUND AND AIMS: Glargine improves glucose control and reduces the risk of nocturnal hypoglycemia compared with neutral protamine Hagedorn (NPH) insulin. To date, only one study has measured the effects of glargine on health-related quality of life (HRQL); the aim of this study was therefore to confirm the beneficial effects of glargine on disease-specific HRQL in type 1 diabetes. METHODS AND RESULTS: Forty-seven patients (mean age, 46 range, 25-74; males, 54%) with diabetes of at least 1-year duration, and with suboptimal glucose control under intensive insulin treatment (IIT), were switched from NPH to glargine. Forty patients maintained on IIT were used as controls. Diabetes-related HRQL was assessed using the Well-being Enquiry for Diabetics (WED), before and after a 6- to 8-month switch to glargine. An 11-item questionnaire based upon diabetes-specific issues was used to assess treatment satisfaction and perceived changes after switching. On glargine, the mean glycosylated hemoglobin decreased by 0.7% (treatment vs. baseline, P

Only a few data are available on the survival rate following out-of-hospital cardiac arrest in different Italian settings. We report an analysis of a 10-year experience in a mixed rural/urban setting, the main variables associated with survival, and the preliminary results of the implementation of an automated external defibrillator (AED) programme operated by lay volunteers on the effectiveness of the existing Emergency Medical Service (EMS).We report data from an observational cohort study on all adults, resuscitated from witnessed cardiac arrest between 1994 and 2004 in the district area of Forlì (Italy). The AED programme was introduced in 2002. Entry variables, time intervals and nodal events were tested according to Utstein recommendations. The predictors of favourable outcomes (Overall Performance Category 1-2) were identified by logistic regression analysis.The witnessed cardiac arrest rate was 27/100,000 population per year (95% confidence interval, 18-38). The initial rhythm was shockable in 241/479 cases (50.3%). After resuscitation, 55 (11.5%) subjects had a favourable outcome at discharge and 38 (7.9%) at 1 year. Time-to-treatment was longer for EMS than for AED-equipped units (median, 8 min interquartile range, 6-10 (467 cases) versus 6 min interquartile range, 4-8 (13 cases); P0.013), but the final results of the AED programme were poor, with only 1 subject saved/171,000 inhabitants in 2 years. Positive outcome predictors were male sex, younger age, shockable rhythms, low number of defibrillations, and no history of hypertension, diabetes, myocardial infarction or congestive heart failure.Even in a mixed urban/rural setting, survival from out-of-hospital cardiac arrest is dependent on well-known predictors. In our setting, the number of cases saved by an AED programme is limited when accompanied by an efficient traditional EMS. The allocation of resources to an AED programme should be reconsidered in a mixed rural/urban setting.

Riassunto Ogni tentativo di misurare l’apporto calorico è necessariamente approssimativo, qualora non si giunga alla registrazione e pesatura meticolosa degli alimenti, peraltro gravata da errori. Abbiamo sviluppato un questionario autosomministrato, basato su 20 gruppi di alimenti. Per ognuno, il paziente deve indicare la frequenza settimanale e la porzione su una scala a 5 punti. Le calorie delle porzioni sono conteggiate per multipli di 50. Attraverso un semplice calcolo si giunge alla definizione delle calorie medie giornaliere su base settimanale. Dopo un periodo di taratura, per approssimazioni successive, siamo giunti ad una versione definitiva, testata su 123 soggetti consecutivi nei confronti dell’intervista semistrutturata condotta dalla dietista. L’apporto calorico stimato dal questionario (2388 ± SD 798 kcal/die in 100 questionari validi per l’analisi) non risulta significativamente diverso da quello misurato nell’inchiesta (2317 ± 676; P = 0.191; t appaiata) ed esiste tra le due misurazioni una buona correlazione (r 2 = 0.585; P< 0.0001), in un range calorico misurato dall’intervista compreso tra 946 e 5080 kcal/die. Il questionario sovrastima l’apporto calorico nel primo quintile dell’intervista (range 900 – 1833 kcal/die; ? = +163 ± SD 343 kcal/die; P = 0.047), ma mantiene una buona correlazione tra 1500 e 3000 kcal/die (? = 65 kcal/die), nel quale si colloca l’83% dei casi analizzati. Lo strumento può essere utile per indagini epidemiologiche in soggetti motivati a perdere peso, o come ausilio ai medici di medicina generale in assenza di dietisti in una politica di controllo dell’obesità. English Summary Any attempt to measure calorie intake is approximate when foods are not registered and weighted, and several biases may be introduced. We developed a self-administered questionnaire, based on 20 items, their weekly intake and the average portion on a Likert scale. Portions are given a score as multiple of 50 calories, allowing a simple calculation of the daily intake on a weekly basis. The test was adjusted during the years and its final version was tested in 123 consecutive subjects against a semi-structured interview carried out by a dietitian. Calorie intake measured by the questionnaire (2388 ± SD 798 kcal/day in 100 questionnaires valid for analysis) does not differ from values calculated by interview (2317 ± 676; P = 0.191; paired t), and a good correlation exists between the two measurements (r 2 = 0.585; P< 0.0001) in a calorie range measured by the interview between 946 and 5080 kcal/day. The questionnaire overestimates calorie intake in the first quintile of interview (range, 900 – 1833 kcal/day; ? = +163 ± SD 343 kcal/die; P = 0.047), but maintains a good correlation between 1500 and 3000 kcal/day (? = 65 kcal/day), a range comprising 83% of tested cases. The self-administered instrument may be useful in epidemiological surveys in subjects seeking a weight-losing treatment, or as support to general practitioner in the absence of dietitians.

Background: A comprehensive lifestyle approach is suggested as first-line treatment for the individual features of the metabolic syndrome, but the results in community medicine are usually discouraging. No study has tested the feasibility of an integrated approach between general practitioners (GPs) and specialist centers. Methods: We report the process analysis on baseline data of a randomized study based on the integration between GPs, selecting patients on the basis of a pre-defined grid and specific targets, and a specialist center, providing informative material and arranging courses of counseling and cognitive-behavioral therapy, using a shared database. After initial visits by GPs for clinical assessment and motivation to treatment, patients were randomly assigned to: (a) prescriptive diet, managed by GPs; (b) counseling (four group lessons); (c) cognitive-behavioral treatment (12 group lessons), both managed by specialist center. Data of the first 503 subjects were compared with those of 139 cases self-referring to the specialist center for the treatment of obesity. Results: Subjects enrolled by GPs were more frequently males, had lower obesity grades, and a higher number of features of metabolic syndrome, compared with the control group. Only 10% of subjects randomized to counseling and 27% randomized to behavior declined participation in the intensive treatments; attendance at sessions averaged 90%. GPs were satisfied with their participation and reported that treatments met patients’ needs. Conclusions: An integrated approach to lifestyle changes between GPs and a specialist center is feasible in the metabolic syndrome and may be cost-effective, considering the high burden of disease.

Outcome research in obesity is aimed at the identification of clinically meaningful goals. Over the years, the focus has moved from surrogate health markers to cardiovascular risk and survival. The 7–10% weight loss recommended by guidelines is a target easily attained with any treatment, but does not guarantee physical and psychological benefits unless it is accompanied by weight loss maintenance, a target very difficult to achieve with either behavior treatment or pharmacological intervention. A reduced cardiovascular risk profile is associated with weight loss, irrespective of the treatment program. In contrast, no controlled studies have so far documented an increased survival, but evidence has been provided by epidemiological surveys. Also bariatric surgery, promoting a larger weight loss and good weight loss maintenance, has failed to demonstrate an improved survival. Health-related quality of life is an additional significant outcome, approved by international agencies. Concern regarding a possible detrimental effect of dieting on mood and depression is not substantiated by the results of controlled studies. The high prevalence of obesity and its consequences pose a serious and unresolved challenge to the medical community and the definition of outcome measures is a key issue for the assessment of results. Drug Dev. Res. 67:260–270, 2006. © 2006 Wiley-Liss, Inc.

Negli ultimi 15 anni si è progressivamente affermato il concetto che vede nella steatosi epatica il momento iniziale di un danno epatico potenzialmente progressivo. La steatosi epatica nonalcolica (NAFLD) ha assunto quindi una notevole importanza, configurandosi come una via metabolica alla cirrosi ed al carcinoma epatocellulare. Altri agenti eziologici, in particolare il virus C dell’epatite, possono interagire con la malattia metabolica attraverso vie non interamente chiarite. Il diabete tipo 2, l’obesità e la dislipidemia rimangono i principali fattori di rischio della NAFLD, che viene ad essere considerata come l’espressione epatica della Sindrome Metabolica (SM). Una serie importante di studi ha messo in luce i rapporti tra NAFLD e SM, il rischio di malattia epatica associato alle varie condizioni che caratterizzano la SM, l’importanza dell’insulino resistenza come denominatore comune. Resta da chiarire il meccanismo di progressione del danno epatico dalla semplice steatosi alla steatoepatite ed infine alla cirrosi, e la ragione per la quale si giunge solo in alcuni casi alla malattia epatica terminale, in altri (la grande maggioranza) agli eventi cardiovascolari. L’epidemia di obesità e diabete del mondo occidentale prospetta un aumento significativo dei casi di malattia epatica su base metabolica per i prossimi anni. Progetti di prevenzione e di intervento basati sullo stile di vita divengono quindi particolarmente urgenti anche per quanto riguarda la epatopatia metabolica. Riassunto In the last 15 years evidence has been accumulating suggesting that hepatic steatosis may be the starting point for a progressive liver disease. Nonalcoholic steatohepatitis (NAFLD) is now considered a metabolic pathway to advanced liver disease, cirrhosis and hepatocellular carcinoma. Liver disease of other etiology, namely hepatitis C virus, may interact with NAFLD, although the underlying mechanism(s) have not been fully elucidated. Type 2 diabetes mellitus, obesity and dyslipidemia are the principal factors associated with NAFLD, which is now considered the hepatic expression of Metabolic Syndrome (MS). Several studies have dealt with the relationship of NAFLD and MS, the risk of liver disease associated with the classical features of MS, the importance of insulin resistance as the common soil of different diseases. We still need to clarify the mechanism(s) responsible for liver disease progression from pure fatty liver, to steatohepatitis and to cirrhosis, and the reason(s) why only a few NAFLD cases progress to terminal liver failure while others (the majority) will have a cardiovascular outcome. The epidemics of obesity and diabetes of Western countries is expected to produce a significant increase of metabolic liver disease in the next years. Prevention and intervention programs based on lifestyle are therefore mandatory to reduce the burden of metabolic liver disease.

OBJECTIVES Metformin proved useful in the treatment of non-alcoholic fatty liver disease (NAFLD), but its superiority over nutritional treatment and antioxidants has never been demonstrated. We aimed to compare the usefulness of metformin vs. prescriptive diet or vitamin E. METHODS In an open label, randomized trial, non-diabetic NAFLD patients were given metformin (2 g/day; n = 55) for 12-months. The control cases were given either given vitamin E (800 IU/day; n = 28) or were treated by a prescriptive, weight-reducing diet (n = 27). Outcome measures were liver enzymes, insulin resistance (homeostasis model assessment), parameters of the metabolic syndrome, and histology. RESULTS: Aminotransferase levels improved in all groups, in association with weight loss. The effects in the metformin arm were larger (P < 0.0001), and alanine aminotransferase normalized in 56% of cases (Odds Ratio vs. Controls, 3.11; 95% Confidence Interval, 1.56 – 6.20; P = 0.0013). In multivariate analysis, metformin treatment was associated with higher rates of aminotransferase normalization, after correction for age, gender, basal aminotransferases and change in BMI (OR, 5.98; 95% CI, 2.05 – 17.45). Differences were maintained when the two control groups were separately analyzed. The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm (P = 0.001, signed rank test). A control biopsy in 17 metformin-treated cases (14 non-responders) showed a significant decrease in liver fat (P = 0.0004), necroinflammation and fibrosis (P = 0.012 for both). No side effects were observed during metformin treatment. CONCLUSIONS: Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling. Limited histological data support an association between improved aminotransferases and biopsy findings which require confirmation in a double-blind trial with appropriate statistical power based on liver histology.

Purpose of review Branched-chain amino acids (BCAAs) have a peculiar role in whole-body nitrogen metabolism. BCAAs are a substrate for protein synthesis, and have been used to conserve or restore muscle mass in advanced liver disease. In addition, the competitive action of BCAAs on amino acid transport across the blood-brain barrier may improve hepatic encephalopathy. Recent findings The effects of branched-chain amino acids on nutrition and ultimately on prognosis of patients with advanced cirrhosis have been confirmed in a large multicenter, long-term trial. Similarly, BCAA treatment improved the prognosis of patients with hepatocellular carcinoma, treated by chemoembolization. The mechanism for the beneficial effects of BCAA is likely to depend on the stimulating activity of BCAA on hepatocyte growth factor, favoring liver regeneration. Summary After an experience of 25 years with branched-chain amino acids, new data supports their beneficial effect in liver diseases. Although the number of patients who cannot tolerate dietary proteins in amounts sufficient to meet their increased catabolism is probably low, in this specific setting BCAAs remain the sole treatment of proved efficacy.

Fatty liver at ultrasounds, with/without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of nonalcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome. We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; n = 799) and gamma-glutamyltranspeptidase (GGT; n =459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR)(n =522). Median ALT and AST increased with increasing obesity class (P =0.001 and P =0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (P

Insulin resistance is the pathophysiologic hallmark of nonalcoholic fatty liver disease (NAFLD), one of the most common causes of chronic liver disease in Western countries. In this article, we review the definition, the methods for the quantitative assessment of insulin action, the pathophysiology of insulin resistance and its role in the pathogenesis of chronic liver disease. Increased free fatty acid (FFA) flux from adipose tissue to non-adipose organs, which is a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a pro-inflammatory state, which may be limited to the liver or more extensively expressed throughout the body. Insulin resistance is the common soil of the metabolic syndrome and its related features. It is a systemic disease affecting the nervous system, muscle, pancreas, kidney, heart, and the immune system, in addition to the liver. A complex interaction between genes and the environment favors or enhances insulin resistance and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic liver disease is associated with multiple features of the metabolic syndrome and the risk of progressive liver disease should no longer be underestimated in subjects with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing insulin resistance in the liver (metformin) and in the periphery (thiazolidinediones) are discussed.

The association of metabolic disorders with liver disease is receiving increasing attention in the gastroenterological community. Cohort studies have shown that advanced liver disease may stem from metabolic disorders, via fatty liver, non-alcoholic steatohepatitis, cryptogenic cirrhosis, and eventually hepatocellular carcinoma. In both obesity and diabetes, deaths from cirrhosis are higher than expected, mainly in subjects with no or moderate alcohol consumption, but high rates of fatty liver disease have been associated with all features of the metabolic syndrome. Also the risk of hepatocellular carcinoma is higher than normal, being dependent on body mass index (BMI) in obesity, and independent of age, BMI, gender and race in diabetes. Finally, metabolic liver disease may interact with hepatitis C virus infection, increasing the risk of steatosis and liver disease progression, as well as reducing the chances of an effective antiviral treatment. There is evidence that treatments aimed at reducing insulin resistance are also effective in improving liver histology. Although cardiovascular disease remains the major cause of increased morbidity and excess mortality in metabolic disorders, the risk of progressive liver disease should no longer be underestimated, being a threat to millions of people at risk in the present epidemics of obesity and diabetes, and therapeutic strategies need to be tested.

We evaluated the prevalence of disordered eating behavior in 168 unselected outpatients with type 2 diabetes and the effects on the health related quality of life (HRQL). Subjects in generally good glycemic control, treated by diet or oral hypoglycemic agents (58% M; 63.8 ± SD 10.1 years; BMI, 29.7 ± 5.9 kg/m2) completed self-administered questionnaires for HRQL (SF-36) and eating behavior (Three-Factor Eating Questionnaire (TFEQ); Binge Eating Scale (BES)). Data on HRQL were computed as effect-sizes in comparison to population norm. The prevalence of altered TFEQ scales was not different between genders, and varied between 22.1% (disinhibition) and 41.4% (restriction), but only 6.7% had a positive BES score. Age (OR, 0.58 for decade; 95% CI, 0.39 – 0.87), duration of diabetes (OR, 1.33 for 5 years; 1.01 – 1.74) and BMI (OR, 1.11; 1.04 – 1.18) were predictive for the presence of disinhibition. BMI also predicted hunger (OR, 1.16; 1.08 – 1.25). SF36 domains were not different in relation to positive BES. Disinhibition at TFEQ was significantly associated with poor Social Functioning (P = 0.018) and Role-Emotional (P = 0.022), whereas hunger was associated with poor Physical Functioning (P = 0.010), Role-Physical (P = 0.0014), Social Functioning (P = 0.015) and Role-Emotional (P = 0.0001). Metabolic control, duration of diabetes, and the presence of complications were not associated with HRQL. A disordered eating behavior may be present in type 2 diabetes patients, and is associated with poor HRQL. This condition must be considered for an olistic approach to weight control.

Dalle Grave R, Melchionda N. Calugi S. Centis E, Tufano A, Fatati G. Fusco MA, Marchesini G (Villa Garda Hospital, Garda. Verona; University of Bologna, Bologna; University Hospital, San Donato Milanese, Milan; Santa Maria Hospital, Terni; and San Camillo-Forlanini Hospital, Rome; Italy). Continuous care in the treatment of obesity: an observational multicentre study. J Intern Med 2005; 258: 265-273. Objectives. To investigate weight loss and reasons for attrition in obese patients on long-term continuous care. Design. Observational study with 36 months of follow-up. Setting. Fifteen Italian obesity centres applying a continuous care model of medical treatment. Subjects. One thousand treatment-seeking obese subjects (785 females, median age 45.1 years, median BMI 37.4 kg m -2 ). Weight loss expectations were systematically recorded at baseline. Interventions. An initial intensive treatment period (3-6 months) was followed by a less intensive continuous care (a follow-up control every 2-4 months). Main outcome measures. Attrition, reasons for treatment interruption and BMI change. Data were recorded by telephone interview in dropouts. Results. Only 157 patients (15.7%) were in continuous treatment at 36 months. The main reasons of attrition were logistics, unsatisfactory results and lack of motivation. The only basal predictor for continuous care was lower Expected One-Year BMI Loss (P = 0.016). The probability of dropout increased systematically for any 5% expected BMI loss (Hazard ratio, 1.05; 96% confidence interval, 1.01-1.09). The mean percentage weight loss was greater in continuers (5.2% vs. 3.0% in dropouts; P = 0.016). However, the dropouts satisfied with the results or confident to lose additional weight without professional help reported a mean weight loss of 9.6% and 6.5% respectively. Discussion. Continuous care produces long-term weight loss only in a subgroup of obese patients seeking treatment in medical centres. The finding that subgroups of dropouts report long-term weight loss has implication for the treatment of obesity.

Objective: To investigate the influence of weight loss expectations (Expected One-Year BMI Loss, Dream and Maximum Acceptable BMI) on attrition in obese patients seeking treatment. Research Methods and Procedures: 1,785 obese subjects (1,393 females; median age 46 years; median BMI, 36.7 kg/m2), seeking treatment in 23 medical Italian centers were evaluated. Baseline diet and weight history, weight loss expectations, and primary motivation for seeking treatment (health or improving appearance) were systematically recorded. Psychiatric distress, binge eating and body image dissatisfaction were tested at baseline by self-administered questionnaires (Symptom CheckList-90, Binge Eating Scale and Body Uneasiness Test). Attrition and BMI change at 12 months were prospectively recorded. Results: At 12 months, 923 of 1,785 patients (51.7%) had discontinued treatment. Compared with continuers, dropouts had a significantly lower age, a lower age at first dieting, lower Dream BMI, a higher Expected One-Year BMI Loss, and a higher Weight Phobia. At logistic regression analysis, the strongest predictors of attrition at 12 month were lower Age, and higher Expected One-Year BMI Loss. The risk of drop-out increased systematically for unit increase in Expected BMI loss at 12 months (hazard ratio, 1.12; 95% confidence interval, 1.04 – 1.20; P = 0.0018). The risk was particularly elevated in the first 6 months. Discussion: Baseline weight loss expectations are independent cognitive predictors of attrition in obese patients entering a weight-losing program; the higher the expectations the higher attrition at 12 months. Unrealistic weight goals should be tackled since the very beginning of treatment.

Recommendations on treatment of patients with head injury were recently proposed by the National Institute for Clinical Excellence (NICE). We tested the clinical performance of NICE variables versus the proposal of the Neurotraumatology Committee of the World Federation of Neurosurgical Societies (NCWFNS). Over a 5-year period, the clinical data of 7,955 adolescent and adult patients with mild head injury were prospectively collected and patients were managed according to the NCWFNS proposal. Outcome measures were (a) any post-traumatic lesion; (b) need for neurosurgical intervention; (c) unfavorable outcome (death, permanent vegetative state, severe disability) after 6 months. The predictive value of NICE variables was tested by logistic regression analysis. Three hundred fifty-four patients (6.8%) had intracranial lesions on computed tomography (CT) scan; neurosurgical intervention was needed in 108 patients (1.3%), and an unfavorable outcome occurred in 54 patients (0.7%) at 6-month follow-up. NICE variables were less sensitive than NCWFNS (93.5%; 95% confidence interval 91.0-95.2; vs. 97.8%; 96.1-98.7; p < 0.001), but far more specific (70.0%, 69.0-71.0, vs. 45.9%, 44.8-47.0; p < 0.001) for predicting intracranial lesions. NICE variables were also more specific (66.5%, 65.5-67.5, vs. 43.5%, 42.4-44.6; p < 0.001) in the prediction of neurosurgical intervention. 99.1% of unfavorable outcomes were predicted by both protocols. The CT order rate of NICE was much lower (34.1% vs. 57.1%; p < 0.001). In sum, the variables selected by NICE recommendations, when applied to a typical broad sample of emergency medicine, are a reliable, clinically sensible tool in predicting significant outcomes in patients with mild head injury and are resource saving.

Plasma levels of adiponectin are decreased in patients with Nonalcoholic Fatty Liver Disease (NAFLD), but the relationship between plasma adiponectin, insulin sensitivity and histological features is unclear. In 174 NAFLD patients and 42 controls, we examined plasma adiponectin concentration in relation to: a) lipid profile, indices of insulin resistance, and features of the metabolic syndrome (n = 174); b) hepatic insulin resistance (clamp technique with tracer infusion) (10 patients); and c) histological features at liver biopsy (n = 114). In the whole group, plasma adiponectin levels were higher in females and were significantly associated with age, waist circumference, body mass index, lipid profile, insulin resistance and aminotransferase levels, and predicted the presence of the metabolic syndrome. In stepwise regression, only age, gender, waist circumference, triglycerides and HOMA-R were associated with adiponectin (adjusted R2, 0.329). In NAFLD, adiponectin was independently associated only with age, gender and triglycerides (adjusted R2, 0.245). When histology was added in the analysis, also percent hepatic fat was fit in the model (adjusted R2, 0.221), Histological parameters of necroinflammation and fibrosis were not associated with adiponectin. Adiponectin was inversely correlated with insulin-suppressed endogenous glucose production during the clamp (P = 0.011). The results demonstrate that decreased levels of circulating adiponectin in NAFLD are related to hepatic insulin sensitivity and to the amount of hepatic fat content. Hypoadiponectinemia in NAFLD is part of a metabolic disturbance characterized by ectopic fat accumulation in the central compartment.

Study objective: The identification of risk factors for recurrent motor vehicle crashes is the basis for prevention, but very few studies have been published on predictors of recurrence. We aimed to determine the main variables predicting recurrence in subjects attending an emergency department for injuries after motor vehicle crash. Methods: In a 5-year follow-up, we studied 2,354 consecutive adult subjects, treated in the emergency department following a motor vehicle crash in 1998. The variables of the original event were tested for predicting recurrence in a Cox proportional hazard model. Results: During follow-up 390/2,325 (16.8%) survivors were treated for injury after a new crash. The overall event rate was 34 per 1,000 subject-years. Four variables (age ?32 years, male sex, night-time crash, and blood alcohol concentration >50 mg/dL) were identified as independent predictors of recurrent crash. After adjustment for sex, age, and night-time, alcohol was the leading predictor (Relative Risk 3.73; 95% Confidence Interval 3.00 – 4.64). In the presence of the four variables, the recurrence rate was as high as 145 (117 – 175) events per 1,000 subject-years, and alcohol per se accounted for over 75% of events. In the absence of the four variables, the rate was as low as 11 (7 – 17) events per 1,000 subject-years. Conclusion: Alcohol is the most powerful behavioral factor predicting recurrent events in subjects treated in an emergency department for injury after motor vehicle crash, together with young age, male gender, and night-time. There is a call to action for prevention of alcohol-on-the-road.

Gli interventi sullo stile di vita finalizzati alla modificazione delle abitudini alimentari e all’attività fisica per il controllo delle malattie metaboliche sono abitualmente condotti con didattica frontale, individualmente o a gruppi di pazienti. Abbiamo sentito la necessità di aggiungere al modello tradizionale la didattica dell’e-learning per raggiungere in modo agile e flessibile i soggetti impossibilitati a frequentare il Servizio. E’ così nato “Gulliver”, un programma di Intervento Nutrizionale Elementare su SINFODIA, una piattaforma sviluppata per la gestione e la fruizione di contenuti didattici attraverso il web accessibile con password. “Gulliver” è suddiviso in moduli e lezioni; i pazienti seguono un percorso formativo sulla “scrivania studenti”, mentre il docente-tutor osserva e valuta il processo di apprendimento sulla “scrivania docente” e tiene contatti @mail con gli studenti. Il progetto è in sperimentazione su un coorte di pazienti affetti da Sindrome Metabolica. Sono qui descritte le funzionalità salienti di “Gulliver” e gli spunti di riflessione legati ad un primo periodo di sperimentazione circa l’utilità e la necessità di implementare l’uso di queste metodologie innovative per far fronte al numero sempre crescente di soggetti che necessitano di un intervento comportamentale. English Summary: Interventions aimed at modifying dietary lifestyle and physical activity in subjects with metabolic diseases are usually carried out individually or by means of frontal sessions. We have developed an e-learning program to improve patients’ adherence to treatment, frequently limited by logistics. “Gulliver” is a program of nutritional counseling using SINFODIA, a platform specifically devoted to the learning process, which can be acceded on the web through userid and password. “Gulliver” is divided into modules and lessons; the patients follow a learning pathway on a “student board”, the teacher/tutor supervises and evaluates the learning process on a “teacher board” and interacts with students through @mail. The project is under test in a cohort of subjects with the metabolic syndrome. We describe the main features of “Gulliver”, and put forward a few considerations regarding its use to cope with the needs of the increasing number of subjects requiring behavioral treatment.

While there is increasing evidence that non-alcoholic fatty liver disease (NAFLD) may be the most common liver disease in Western countries, its prevalence and risk factors have not undergone a formal evaluation in a representative sample of the general population. We therefore performed a cross-sectional study in the town of Campogalliano (Modena, Italy), within the context of the Dionysos Project. Subjects with suspected liver disease (SLD), defined on the basis of elevated serum ALT and GGT activity, HBsAg or HCV-RNA positivity, were matched with randomly selected subjects of the same age and sex without SLD. A total of 311 subjects with and 287 without SLD underwent a detailed clinical, laboratory and anthropometrical evaluation. Fatty liver was diagnosed by ultrasonography and alcohol intake was assessed using a seven-day diary. Multinomial logistic regression was used to detect risk factors for normal liver vs. NAFLD and for alcoholic fatty liver (AFLD) vs. NAFLD. The prevalence of NAFLD was similar in subjects with and without SLD (25 vs. 20%, p = 0.203). At multivariable analysis, normal liver was more likely than NAFLD in older subjects and less likely in the presence of obesity, hyperglycemia, hyperinsulinemia, hypertriglyceridemia and systolic hypertension; AFLD was more likely than NAFLD in older subjects, males and in the presence of elevated GGT and hypertriglyceridemia and less likely in the presence of obesity and hyperglycemia. We conclude that NAFLD is highly prevalent in the general population, is not associated with SLD, but is associated with many features of the metabolic syndrome.

Purpose of review Branched-chain amino acids BCAAs have a peculiar role in whole-body nitrogen metabolism. BCAAs are not only a substrate for protein synthesis, but also modulate several components of the synthetic machinery and help to conserve muscle mass; accordingly several conditions, characterized by protein loss and catabolic status, are likely to benefit from amino acid administration. In addition, the competitive action of BCAAs on amino acid transport across the blood-brain barrier may ultimately alter the synthesis of brain neurotransmitters, involved in neurological diseases. Recent findings Both putative actions of BCAAs have been tested in controlled clinical studies in the last few years. The beneficial effects on nutrition were reported to improve muscle performance, to reduce protein loss during bed-rest, to favor weight loss in obesity, to reduce catabolism in trauma patients, and improve clinical outcomes in patients with advanced cirrhosis. In this last area the effects on nutrition might be coupled with the effects on hepatic encephalopathy mediated by improved neurotransmission, successfully tested in mania, in tardive dyskinesia and spinocerebellar degeneration. Summary After 30-years of investigation with BCAAs, new studies each year provide further evidence supporting their beneficial effect in a variety of diseases. There is a need for long-term, randomized clinical studies, both in the prevention and in the treatment of various pathological conditions.

Objective: To review the results of a comprehensive drug screening as first line diagnostic tool in patients attending an emergency department for suspected drug poisoning. Methods: A comprehensive drug screening was carried out in plasma or urine, or both, of 310 patients combining an HPLC multidrug profiling system and a fluorescence polarisation immunoassay. Results: In 64.2% of cases the screening confirmed the diagnosis of drug poisoning, in 13.9% suspected drugs were measurable at non-toxic concentrations, and in 21.9% no drugs were found. The suspected drugs were fully confirmed in a minority of cases, (symptomatic patients: 28.2% compared with asymptomatic: 16.5%). Symptomatic patients were less likely to have at least one suspected drug (29.6% compared with 57.7%; p

The role of insulin resistance in non-alcoholic fatty liver disease is suggested by laboratory data (hyperinsulinemia and decreased sensitivity to endogenous and exogenous insulin). The clinical association with features of the metabolic syndrome, particularly in the most aggressive stages of the disease, further confirms a causative role. Fat accumulation in the liver may stem either from genetic defects, primarily responsible for insulin resistance, or excessive calorie intake and visceral obesity, and is mediated by adipocytokines (leptin, adiponectin, tumour necrosis factor-alpha). Progression of fatty liver to steatohepatitis may be the result of an imbalance between pro-inflammatory and anti-inflammatory cytokines, triggering the formation of reactive oxygen species and intrahepatic lipid peroxidation. This process may also be promoted or accelerated by pro-oxidant xenobiotics or environmental factors. Insulin resistance provides a target for specific treatment of non-alcoholic fatty liver, and insulin-sensitising agents (metformin or thiazolidinediones) as well as lifestyle changes to reduce visceral adiposity are the most promising therapeutic options. Future trials need to be performed in order to test the long-term effectiveness of these treatments on the basis of clinically relevant histological outcomes.

Background: In mild head injury, predictors to select patients for computed tomography (CT) and/or to plan proper management are needed. The strength of evidence of published recommendations is insufficient for current use. We assessed the diagnostic accuracy and the clinical validity of the proposal of the Neurotraumatology Committee of the World Federation of Neurosurgical Societies on mild head injury from an emergency department perspective. Methods: In a three year period, 5578 adolescent and adult subjects were prospectively recruited and managed according to the proposed protocol. Outcome measures were: (a) any post-traumatic lesion; (b) need for neurosurgical intervention; (c) unfavourable outcome (death, permanent vegetative state or severe disability) after six months. The predictive value of a model based on five variables (Glasgow coma score, clinical findings, risk factors, neurological deficits, and skull fracture) was tested by logistic regression analysis. Findings: At first CT evaluation 327 patients (5.9%) had intracranial post-traumatic lesions. In 16 cases (0.3%) previously undiagnosed lesions were detected after re-evaluation within seven days. Neurosurgical intervention was needed in 71 patients (1.3%) and an unfavourable outcome occurred in 39 cases (0.7%). The area under the ROC curve of the variables in predicting post-traumatic lesions was 0.906 (0.009) (sensitivity 70.0%, specificity 94.1% at best cut off), neurosurgical intervention was 0.926 (0.016) (sensitivity 81.7%, specificity 94.1%), and unfavourable outcome was 0.953 (0.014) (sensitivity 88.1%, specificity 95.1%). Interpretation: The variables prove highly accurate in the prediction of clinically meaningful outcomes, when applied to a consecutive set of patients with mild head injury in the clinical setting of a 1st level emergency department.

Non-alcoholic fatty liver disease is now recognized as a cause of potentially-progressive liver damage, posing patients at risk of advanced liver failure. Unfortunately, the natural history of disease is only partly known, the disease is slowly progressive and therapeutic outcomes are difficult to define. These factors have limited therapeutic trials to pilot studies, and very few randomized-controlled studies are available. The concept that insulin-resistance, coupled with oxidative stress, may be the underlying mechanism responsible for fat accumulation and disease progression points to insulin-sensitizing agents (metformin, thiazolidinediones) as the most promising drugs. They proved effective in reducing enzyme levels in the short period, but very limited information is available on liver histology, not to say progression to liver cell failure. Large, long-term, placebo-controlled randomized studies are eagerly awaited. Outside controlled studies, nutritional counselling and physical exercise aimed at moderate weight loss remain the basis of any therapeutic intervention.