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Background & AimsThere is intense research for drugs able to reduce disease progression in nonalcoholic fatty liver disease. We aimed to test the impact of novel antidiabetic drugs (dipeptidyl‐peptidase‐4 inhibitors – DPP‐4Is,... more
Background & AimsThere is intense research for drugs able to reduce disease progression in nonalcoholic fatty liver disease. We aimed to test the impact of novel antidiabetic drugs (dipeptidyl‐peptidase‐4 inhibitors – DPP‐4Is, glucagon‐like peptide‐1 receptor agonists – GLP‐1RAs, sodium‐glucose cotransporter‐2 inhibitors – SGLT‐2Is) on non‐invasive biomarkers of steatosis (fatty liver index, FLI) and fibrosis (Fibrosis‐4 score, FIB‐4) in patients with type 2 diabetes (T2D).MethodsClinical, anthropometric and biochemical parameters were retrospectively analysed in 637 consecutive T2D patients switched from metformin w/wo sulfonylureas and/or pioglitazone to DPP‐4Is, GLP‐1RAs and SGLT‐2Is in a tertiary care setting. 165 patients maintained on original treatments served as controls. The effects on FLI and FIB‐4 at 6‐ and 12‐month follow‐up were analysed by logistic regression after adjustment for baseline differences, computed by propensity scores, and additional adjustment for changes...
Motivational interviewing (MI) is devised to change unhealthy behaviors by increasing motivation. We adapted MI to a group format for the treatment of relapse during the behavioral treatment of obesity and performed a clinical audit to... more
Motivational interviewing (MI) is devised to change unhealthy behaviors by increasing motivation. We adapted MI to a group format for the treatment of relapse during the behavioral treatment of obesity and performed a clinical audit to evaluate its effectiveness in stopping weight regain. The program was structured in seven weekly sessions, plus a 6-month follow-up. Patients (n = 86) completed a questionnaire on motivation to change in both healthy diet and physical activity, and a self-reported measurement of calorie intake and physical activity at baseline, at program end and at 6-month follow-up. The attendance to the program was high, with only 13 patients (15%) not completing the program and 24% not attending the 6-month follow-up. By the end of follow up, the prevalence of patients in either precontemplation or contemplation was reduced from over 60% at enrollment to approximately 20%, whereas the sum of patients in action or maintenance stages was increased from 9.5% in healt...
The aim of this study was to assess the association between weight-loss maintenance and weight-loss satisfaction, adherence to diet and weight loss, all measured session-by-session during the weight-loss phase of cognitive behavioral... more
The aim of this study was to assess the association between weight-loss maintenance and weight-loss satisfaction, adherence to diet and weight loss, all measured session-by-session during the weight-loss phase of cognitive behavioral therapy. The present exploratory study examined a subgroup of fifty-eight patients who participated in a randomized controlled trial and who lost at least the 10% of their baseline weight. Patients were grouped into weight-loss 'Maintainers' (i.e., those who maintained a weight loss of ≥ 10% of baseline body weight at 6 months after the weight-loss phase) and 'Regainers' (i.e., those who did not maintain > 10% weight loss at 6 months after the weight-loss phase). Body weight, adherence to diet and weight-loss satisfaction were measured session-by-session during the weight-loss phase. Thirteen patients (22.4%) were classified as 'Regainers', and 45 (77.6%) as 'Maintainers'. Compared to 'Maintainers', 'Regain...
Conflicting evidence exists as to whether cognitive mechanisms contribute to weight loss and maintenance. To assess the influence of weight-loss expectations on weight loss, and of weight-loss satisfaction on weight maintenance, in... more
Conflicting evidence exists as to whether cognitive mechanisms contribute to weight loss and maintenance. To assess the influence of weight-loss expectations on weight loss, and of weight-loss satisfaction on weight maintenance, in individuals with severe obesity. A randomized controlled trial comparing two types of energy-restricted diets (high protein vs high carbohydrate) combined with weight-loss cognitive behavioral therapy, conducted over 51 weeks and divided into two phases: weight-loss phase (3 weeks of inpatient treatment and 24 weeks of outpatient treatment) and weight maintenance phase (24 weeks of outpatient treatment). Eighty-eight participants with severe obesity (mean age=46.7 years and mean body mass index=45.6), referred to an eating and weight disorders clinical service, were studied. Body weight was assessed at baseline, and after 3, 27 (end of weight-loss phase), and 51 weeks (end of weight maintenance phase). Weight loss expectations were assessed at the time of...
Background: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic... more
Background: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors). Key Messages: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like ph...
The effectiveness of different programs of physical activity outside randomized studies is difficult to determine. We carried out an audit in two different units where either a supervised physical activity (PA) program or a self-selected... more
The effectiveness of different programs of physical activity outside randomized studies is difficult to determine. We carried out an audit in two different units where either a supervised physical activity (PA) program or a self-selected PA program was in use in individuals with type 2 diabetes or obesity. The supervised PA cohort (n = 101) received progressive gym training (120 min, twice a week for 13 weeks) by a dedicated team, with nutritional counseling during resting periods. The self-selected PA cohort (n = 69) was enrolled in a 13-week cognitive-behavioral program (120 min/week, in groups of 12-15 individuals), chaired by an expert team. Body weight and physical fitness (6-min walk test) were measured at baseline and after 6 and 12 months. Outcome measures were attrition, weight loss ≥10 % initial body weight, 10 % increase in 6-min walk test; their association with a PA program was tested by logistic regression analysis. Attrition rate was lower in the supervised PA group (28 vs. 45 % than in the self-selected cohort, P = 0.023). After adjustment for confounders, the supervised PA program was associated with a lower risk of attrition at 1 year (odds ratio 0.45; 95 % confidence interval, 0.21-0.98) at logistic regression analysis. Body weight similarly decreased in both groups (more rapidly in the supervised PA cohort); also physical fitness improved in a similar way, and no differences in achieved targets of body weight (supervised, 31 %; self-selected, 18 %; P = 0.118) or fitness (supervised, 62 %; self-selected, 49 %; P = 0.312) were demonstrated. Different PA programs produce very similar health benefits, but an initially supervised program has lower attrition rates, which might translate into better outcomes in the long term.
Subjects with nonalcoholic fatty liver disease are at risk of progressive liver failure. Lifestyle changes including weight-loss strategies and increased physical activity remain the first-line approach, but a few pharmacological... more
Subjects with nonalcoholic fatty liver disease are at risk of progressive liver failure. Lifestyle changes including weight-loss strategies and increased physical activity remain the first-line approach, but a few pharmacological treatments have also been successfully tested. Several drugs improve biochemistry, only a few improve histology; in all cases, the results were not sustained after treatment stop. Pharmacological treatment is not so far indicated outside controlled clinical trials with histological outcomes.
ABSTRACT 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... more
ABSTRACT 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.
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the... more
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.
A poor nutritional status has repeatedly been described in advanced liver cirrhosis, but the exact prevalence of the defect and its relation to the aetiology and severity of liver disease in the Italian population are only partly known.... more
A poor nutritional status has repeatedly been described in advanced liver cirrhosis, but the exact prevalence of the defect and its relation to the aetiology and severity of liver disease in the Italian population are only partly known. Anthropometric measurements were carried out in 200 patients with cirrhosis (135 M, 65 F). Liver disease was related to alcohol abuse in 77 cases, but most patients had stopped alcohol for at least 6 months before study. In comparison to a normal elderly Italian and to an age-matched North-American population, 5 to 45% of male patients with cirrhosis and 10 to 30% of females had signs of malnutrition, the proportion being variable according to the test used. Male patients showed a remarkable reduction in muscle mass (30-45% of patients, mainly in the presence of moderate-to-severe or severe liver failure), whereas female patients showed a more remarkable reduction of fat stores (15-30% of cases), with advancing liver failure, and a less severe reduction in muscle mass. No direct effect of alcohol was demonstrated in this selected population.
Polyamines (putrescine, spermidine, and spermine) are widely distributed in animal and vegetal tissues, where their intracellular concentration strictly correlates with normal and pathological cell growth and protein synthesis. By means... more
Polyamines (putrescine, spermidine, and spermine) are widely distributed in animal and vegetal tissues, where their intracellular concentration strictly correlates with normal and pathological cell growth and protein synthesis. By means of a sensitive HPLC technique, the fasting plasma concentrations of polyamines were measured serially in 11 patients who underwent partial hepatic resection because of focal liver lesions. Samples were obtained before surgery and over the next 6 months, during hepatic regeneration. Liver volume was also measured by ultrasound on the basis of the 3 maximum diameters of the liver. From 2 to 4 weeks after surgery, plasma putrescine increased by a maximum of 78%, and spermidine by approximately 50%. No changes were observed in spermine levels. The spermidine/spermine ratio nearly doubled during liver regeneration. The volume of the liver decrease from 1505 [SD 236] ml to 743 [151] ml after resection, and returned to nearly normal values after 6 months (1231 [100] ml, p < 0.05 vs. basal values). The liver regeneration rate was highest 2-4 weeks after resection, and declined thereafter, when prevailing polyamine concentrations returned to normal. These data show that liver regeneration is accompanied by a significant increase in fasting putrescine and spermidine concentrations, which might be biochemical signals of active liver cell regeneration.
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the... more
Nonalcoholic fatty liver disease (NAFLD) is a common and emerging liver disease in adults, paralleling the epidemic of obesity and diabetes, and leading to worrisome events (hepatocellular carcinoma and end-stage liver disease). In the last years, mounting evidence added insights about epidemiology, natural history, diagnosis and lifestyle-based or drug treatment of NAFLD. In this rapidly evolving scenario, members of the Associazione Italiana per lo Studio del Fegato (AISF), the Società Italiana di Diabetologia (SID) and the Società Italiana dell'Obesità (SIO) reviewed current knowledge on NAFLD. The quality of the published evidence is graded, and practical recommendations are made following the rules and the methodology suggested in Italy by the Centro Nazionale per l'Eccellenza delle cure (CNEC) and Istituto Superiore di Sanità (ISS). Whenever possible, recommendations are placed within the context the Italian Healthcare system, with reference to specific experience and local diagnostic and management resources. Level of evidence: Level of evidence of recommendations for each PICO question were reported according to available evidence.
Background: Lifestyle interventions aimed at weight loss have been associated with improved liver enzymes, reduced intrahepatic triglyceride content, and improved histology (including reduced fibrosis stage). Objective: To revise the... more
Background: Lifestyle interventions aimed at weight loss have been associated with improved liver enzymes, reduced intrahepatic triglyceride content, and improved histology (including reduced fibrosis stage). Objective: To revise the evidence on the beneficial effects of lifestyle changes accumulated since 2015, following the publication of the pivotal Cuban experience with histologic outcome. Methods: A PubMed search covering the period 2015 to July 2019 was carried out. All retrieved references were analyzed and double-checked by authors. Results: 20 new studies were identified; in addition, two relevant studies provided new evidence. Thirteen studies were classified as randomized, controlled studies, three as proof-of-concept/pilot studies, four as cohort observational studies. In an attempt to maintain a closer contact between participants and the treatment center, a study implemented regular phone calls, another an e-mail service, a third was based on text messages, and finally...
SummaryBackgroundBlood tests of liver injury are less well validated in non‐alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis.AimsTo improve the validation of three blood tests used in NAFLD patients,... more
SummaryBackgroundBlood tests of liver injury are less well validated in non‐alcoholic fatty liver disease (NAFLD) than in patients with chronic viral hepatitis.AimsTo improve the validation of three blood tests used in NAFLD patients, FibroTest for fibrosis staging, SteatoTest for steatosis grading and ActiTest for inflammation activity grading.MethodsWe pre‐included new NAFLD patients with biopsy and blood tests from a single‐centre cohort (FibroFrance) and from the multicentre FLIP consortium. Contemporaneous biopsies were blindly assessed using the new steatosis, activity and fibrosis (SAF) score, which provides a reliable and reproducible diagnosis and grading/staging of the three elementary features of NAFLD (steatosis, inflammatory activity) and fibrosis with reduced interobserver variability. We used nonbinary‐ROC (NonBinAUROC) as the main endpoint to prevent spectrum effect and multiple testing.ResultsA total of 600 patients with reliable tests and biopsies were included. Th...

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