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SN biopsy with IP is fast and discovers more SNs and more invasions than ACL.

ObjectiveClinical diagnosis and approval of new medications for non-alcoholic steatohepatitis (NASH) require invasive liver biopsies. The aim of our study was to identify non-invasive biomarkers of NASH and/or liver fibrosis.DesignThis multicentre study includes 250 patients (discovery cohort, n=100 subjects (Bariatric Surgery Versus Non-alcoholic Steato-hepatitis - BRAVES trial); validation cohort, n=150 (Liquid Biopsy for NASH and Liver Fibrosis - LIBRA trial)) with histologically proven non-alcoholic fatty liver (NAFL) or NASH with or without fibrosis. Proteomics was performed in monocytes and hepatic stellate cells (HSCs) with iTRAQ-nano- Liquid Chromatography - Mass Spectrometry/Mass Spectrometry (LC-MS/MS), while flow cytometry measured perilipin-2 (PLIN2) and RAB14 in peripheral blood CD14+CD16− monocytes. Neural network classifiers were used to predict presence/absence of NASH and NASH stages. Logistic bootstrap-based regression was used to measure the accuracy of predicting liver fibrosis.ResultsThe algorithm for NASH using PLIN2 mean florescence intensity (MFI) combined with waist circumference, triglyceride, alanine aminotransferase (ALT) and presence/absence of diabetes as covariates had an accuracy of 93% in the discovery cohort and of 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery cohort and 88% and 100% in the validation cohort, respectively.The area under the receiver operating characteristic (AUROC) for NAS level prediction ranged from 83.7% (CI 75.6% to 91.8%) in the discovery cohort to 97.8% (CI 95.8% to 99.8%) in the validation cohort.The algorithm including RAB14 MFI, age, waist circumference, high-density lipoprotein cholesterol, plasma glucose and ALT levels as covariates to predict the presence of liver fibrosis yielded an AUROC of 95.9% (CI 87.9% to 100%) in the discovery cohort and 99.3% (CI 98.1% to 100%) in the validation cohort, respectively. Accuracy was 99.25%, sensitivity 100% and specificity 95.8% in the discovery cohort and 97.6%, 99% and 89.6% in the validation cohort. This novel biomarker was superior to currently used FIB4, non-alcoholic fatty liver disease fibrosis score and aspartate aminotransferase (AST)-to-platelet ratio and was comparable to ultrasound two-dimensional shear wave elastography.ConclusionsThe proposed novel liquid biopsy is accurate, sensitive and specific in diagnosing the presence and severity of NASH or liver fibrosis and is more reliable than currently used biomarkers.Clinical trialsDiscovery multicentre cohort: Bariatric Surgery versus Non-Alcoholic Steatohepatitis, BRAVES, ClinicalTrials.gov identifier: NCT03524365.Validation multicentre cohort: Liquid Biopsy for NASH and Fibrosis, LIBRA, ClinicalTrials.gov identifier: NCT04677101.

While it has been shown that climate change anxiety (emotional distress response to climate change) can enhance pro-environmental behaviours (PEBs) in some subjects, in others it can induce eco-paralysis, thus leading individuals to avoid any form of engagement in actions against climate change. This study aims to clarify which factors influence the relationship between climate change anxiety and the disposition to PEBs, focusing on the role of self-efficacy as a mediating factor. A cross-sectional study was conducted on 394 healthy subjects living in Italy who completed the Pro-Environmental Behaviours Scale (PEBS), the General Self-Efficacy scale (GSE), and the Climate Change Anxiety Scale (CCAS). As a result, the mediation model showed a positive direct effect of the cognitive impairment subscale of CCAS on PEBS and an indirect negative effect of the cognitive impairment subscale of CCAS on PEBS mediated by GSE. These findings show that climate change anxiety has simultaneously two different effects on individuals: it directly encourages PEBs, and indirectly may have detrimental effects on PEBs such as eco-paralysis. Consequently, therapeutic approaches to treat climate change anxiety should not be aimed at rationalising irrational thoughts but rather at helping patients develop coping strategies such as PEBs which, in turn, foster self-efficacy.

All the nomograms were good discriminators, but the alternative developed model showed the best predictive accuracy in this Italian breast cancer sample. We still confirm that these models, very accurate in the institution of origin, require a new validation if used on other populations of patients.

Context Non-alcoholic steatohepatitis(NASH)is considered as the hepatic counterpart of the metabolic syndrome. Objective To investigate the determinants of NASH reversal in patients undergoing biliopancreatic diversion(BPD)in a 5-year follow-up study. Design Prospective Study, Policlinico Universitario Agostino Gemelli Participants 37 patients underwent fine-needle liver biopsy during BPD. Nine of them had a negative liver biopsy for NASH and were excluded. Ultrasonography-guided percutaneous liver biopsy was obtained at 5 years after operation. Intervention Biliopancreatic Diversion and liver biopsy Main outcome measures The primary outcome of our study was histologic NASH reversal, at 5-years follow-up. To better characterize the clinical variables involved in the resolution of NASH, we also compared patients without histologic NASH resolution at 5 years, with those in whom NASH had disappeared. Results At follow-up, NASH reversed in 56.5% of the patients. NAFLD Activity-Score(NAS)improved from 3.33±1.15 to 1.84±1.10(P<0.0001).Fibrosis reversed in 16% of the patients(P=0.022)and in 32% improved(95% CI, 0.05-0.54).No significant differences in BMI or clinical parameters changes explained the effect of surgery on NASH, apart from the measure insulin sensitivity post-surgery. HOMA-IR decreased from 3.31±1.72 at baseline to 1.73±1.08(P<0.0001)after BPD and Matsuda index improved from 2.66±1.79 to 4.73±3.05(P<0.0001).Lipid profile normalized(total-cholesterol from 4.75±1.18 to 3.32±0.77mmol/l, P<0.0001; LDL-cholesterol from 2.92±0.91 to 1.60±0.51mmol/l, P=0.0001; HDL-cholesterol from 0.97±0.33 to 1.10±0.35mmol/l, P=0.023; triglycerides from 2.52±1.6 to 1.47±0.67 mmol/l, P=0.003).Neural network analysis showed that end-study Matsuda index discriminated between responders and non-responders with high accuracy[receiver operating characteristic curve(ROC)area-under-the curve(AUC)0.98%]. Conclusion Remission of NASH is driven by reversal of whole-body insulin resistance post-intervention.

Nonalcoholic fatty-liver disease (NAFLD) is the most common cause of liver-related mortality. NAFLD is associated with obesity, hepatic fat accumulation and insulin-resistance, all of which contribute to its pathophysiology. Weight-loss is the main therapy for NAFLD and metabolic surgery is the most effective treatment for morbid obesity and its metabolic comorbidities. Although has been reported that Roux-en-Y gastric bypass can reverse NAFLD, it is unclear if such effects result from reduced weight, from a less calorie-intake or from the direct influence of surgery on mechanisms contributing to NAFLD. We aim to investigate whether gastrointestinal (GI) bypass surgery can induce direct effects on hepatic fat accumulation and insulin-resistance, independently of weight reduction. Twenty Wistar rats under a high-fat diet underwent duodenal-jejunal-bypass (DJB) or sham-operation and were pair-fed (PF) for 15 weeks after surgery to obtain a matched weight. Outcome measures include ectopic fat deposition, expression of genes and proteins involved in fat metabolism, insulin-signaling and gluconeogenesis in liver and muscle. Despite no differences in body-weight and calorie-intake, DJB showed lower ectopic fat accumulation, improved peripheral and hepatic insulin-sensitivity, and enhanced lipid droplet degradation. In both tissues DJB increased insulin-signaling while hepatic key enzymes involved in gluconeogenesis and de novo lipogenesis were decreased. These findings suggest that DJB can reverse, independently of weight loss, ectopic fat deposition and insulin-resistance, two features of NAFLD that share a mutual pathway, in which Perilipin-2 (PLIN2) seems to be the main player, supporting further investigation into strategies that target the gut to treat metabolic liver diseases.

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